Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status.

PubMed

Léger, Thibault; Charrier, Alice; Moreau, Clarisse; Hininger-Favier, Isabelle; Mourmoura, Evangelia; Rigaudière, Jean-Paul; Pitois, Elodie; Bouvier, Damien; Sapin, Vincent; Pereira, Bruno; Azarnoush, Kasra; Demaison, Luc

2017-07-01

If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll-like receptor-9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF- α and IL-1 β In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham-operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF- α and gene expression of IL-1 β and TNF- α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF- α and IL-1 β on the cardiac function is known to occur at very high concentrations. The influence of low- to moderate-grade inflammation on the myocardial mechanical behavior must thus be revisited. © 2017 French National Institute of Agronomical Research (INRA). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Can Functional Cardiac Age be Predicted from ECG in a Normal Healthy Population

NASA Technical Reports Server (NTRS)

Schlegel, Todd; Starc, Vito; Leban, Manja; Sinigoj, Petra; Vrhovec, Milos

2011-01-01

In a normal healthy population, we desired to determine the most age-dependent conventional and advanced ECG parameters. We hypothesized that changes in several ECG parameters might correlate with age and together reliably characterize the functional age of the heart. Methods: An initial study population of 313 apparently healthy subjects was ultimately reduced to 148 subjects (74 men, 84 women, in the range from 10 to 75 years of age) after exclusion criteria. In all subjects, ECG recordings (resting 5-minute 12-lead high frequency ECG) were evaluated via custom software programs to calculate up to 85 different conventional and advanced ECG parameters including beat-to-beat QT and RR variability, waveform complexity, and signal-averaged, high-frequency and spatial/spatiotemporal ECG parameters. The prediction of functional age was evaluated by multiple linear regression analysis using the best 5 univariate predictors. Results: Ignoring what were ultimately small differences between males and females, the functional age was found to be predicted (R2= 0.69, P < 0.001) from a linear combination of 5 independent variables: QRS elevation in the frontal plane (p<0.001), a new repolarization parameter QTcorr (p<0.001), mean high frequency QRS amplitude (p=0.009), the variability parameter % VLF of RRV (p=0.021) and the P-wave width (p=0.10). Here, QTcorr represents the correlation between the calculated QT and the measured QT signal. Conclusions: In apparently healthy subjects with normal conventional ECGs, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG results. Because some parameters in the regression formula, such as QTcorr, high frequency QRS amplitude and P-wave width also change with disease in the same direction as with increased age, increased functional age of the heart may reflect subtle age-related pathologies in cardiac electrical function that are usually hidden on conventional ECG.

Skin temperature and core-peripheral temperature gradient as markers of hemodynamic status in critically ill patients: a review.

PubMed

Schey, Bernadette M; Williams, David Y; Bucknall, Tracey

2010-01-01

To examine the evidential basis underpinning the monitoring of skin temperature and core-peripheral temperature gradient as elements of hemodynamic assessment in critically ill and adult cardiac surgical patients. Twenty-six studies examining the efficacy of skin temperature or temperature gradient as markers of hemodynamic status were selected as part of an integrative review. Evidence pertaining to the efficacy of these parameters as markers of cardiac function is equivocal and has not been well appraised in the adult cardiac surgical population. Skin temperature and systemic vascular resistance are also affected by factors other than cardiac output. Skin temperature and core-peripheral temperature gradient should not be considered in isolation from other hemodynamic parameters when assessing cardiac status until they are validated by further large-scale prospective studies. 2010. Published by Mosby, Inc.

Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats.

PubMed

Tanajak, Pongpan; Pintana, Hiranya; Siri-Angkul, Natthaphat; Khamseekaew, Juthamas; Apaijai, Nattayaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2017-02-01

Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks. Metabolic parameters, heart rate variability (HRV), cardiac mitochondrial function, left ventricular (LV) and fibroblast growth factor (FGF) 21 signaling pathway were determined. Rats on a HFD developed insulin and FGF21 resistance, oxidative stress, cardiac mitochondrial dysfunction and impaired LV function. Rats on CR alone showed both decreased body weight and visceral fat accumulation, whereas vildagliptin did not alter these parameters. Rats in CR, vildagliptin and CR plus vildagliptin subgroups had improved insulin sensitivity and oxidative stress. However, vildagliptin improved heart rate variability (HRV), cardiac mitochondrial function and LV function better than the CR. Chronic HFD consumption leads to obese-insulin resistance and FGF21 resistance. Although CR is effective in improving metabolic regulation, vildagliptin provides greater efficacy in preventing cardiac dysfunction by improving anti-apoptosis and FGF21 signaling pathways and attenuating cardiac mitochondrial dysfunction in obese-insulin-resistant rats. © 2017 Society for Endocrinology.

Right ventricular functional analysis utilizing first pass radionuclide angiography for pre-operative ventricular assist device planning: a multi-modality comparison.

PubMed

Avery, Ryan; Day, Kevin; Jokerst, Clinton; Kazui, Toshinobu; Krupinski, Elizabeth; Khalpey, Zain

2017-10-10

Advanced heart failure treated with a left ventricular assist device is associated with a higher risk of right heart failure. Many advanced heart failures patients are treated with an ICD, a relative contraindication to MRI, prior to assist device placement. Given this limitation, left and right ventricular function for patients with an ICD is calculated using radionuclide angiography utilizing planar multigated acquisition (MUGA) and first pass radionuclide angiography (FPRNA), respectively. Given the availability of MRI protocols that can accommodate patients with ICDs, we have correlated the findings of ventricular functional analysis using radionuclide angiography to cardiac MRI, the reference standard for ventricle function calculation, to directly correlate calculated ejection fractions between these modalities, and to also assess agreement between available echocardiographic and hemodynamic parameters of right ventricular function. A retrospective review from January 2012 through May 2014 was performed to identify advanced heart failure patients who underwent both cardiac MRI and radionuclide angiography for ventricular functional analysis. Nine heart failure patients (8 men, 1 woman; mean age of 57.0 years) were identified. The average time between the cardiac MRI and radionuclide angiography exams was 38.9 days (range: 1 - 119 days). All patients undergoing cardiac MRI were scanned using an institutionally approved protocol for ICD with no device-related complications identified. A retrospective chart review of each patient for cardiomyopathy diagnosis, clinical follow-up, and echocardiogram and right heart catheterization performed during evaluation was also performed. The 9 patients demonstrated a mean left ventricular ejection fraction (LVEF) using cardiac MRI of 20.7% (12 - 40%). Mean LVEF using MUGA was 22.6% (12 - 49%). The mean right ventricular ejection fraction (RVEF) utilizing cardiac MRI was 28.3% (16 - 43%), and the mean RVEF calculated by FPRNA was 32.6% (9 - 56%). The mean discrepancy for LVEF between cardiac MRI and MUGA was 4.1% (0 - 9%), and correlation of calculated LVEF using cardiac MRI and MUGA demonstrated an R of 0.9. The mean discrepancy for RVEF between cardiac MRI and FPRNA was 12.0% (range: 2 - 24%) with a moderate correlation (R = 0.5). The increased discrepancies for RV analysis were statistically significant using an unpaired t-test (t = 3.19, p = 0.0061). Echocardiogram parameters of RV function, including TAPSE and FAC, were for available for all 9 patients and agreement with cardiac MRI demonstrated a kappa statistic for TAPSE of 0.39 (95% CI of 0.06 - 0.72) and for FAC of 0.64 (95% of 0.21 - 1.00). Heart failure patients are increasingly requiring left ventricular assist device placement; however, definitive evaluation of biventricular function is required due to the increased mortality rate associated with right heart failure after assist device placement. Our results suggest that FPRNA only has a moderate correlation with reference standard RVEFs calculated using cardiac MRI, which was similar to calculated agreements between cardiac MRI and echocardiographic parameters of right ventricular function. Given the need for identification of patients at risk for right heart failure, further studies are warranted to determine a more accurate estimate of RVEF for heart failure patients during pre-operative ventricular assist device planning.

Cardiac dimensions and function in female handball players.

PubMed

Malmgren, A; Dencker, M; Stagmo, M; Gudmundsson, P

2015-04-01

Long-term intensive endurance training leads to increased left ventricular mass and increased left ventricular end-diastolic and left atrial end-systolic diameters. Different types of sports tend to give rise to distinct morphological forms of the athlete's heart. However, the sport-specific aspects have not been fully investigated in female athletes. The purpose of the present study was to investigate differences in left and right cardiac dimensions, cardiac volumes, and systolic and diastolic function in elite female handball players compared to sedentary controls. A cross-sectional study of 33 elite female handball players was compared to 33 matched sedentary controls. Mean age was 21.5±2 years. The subjects underwent echocardiography examinations, both 2-dimensional (2DE) and 3-dimensional (3DE). Cardiac dimensions and volumes were quantified using M-mode, 2DE and 3DE. Systolic and diastolic left ventricular functions were also evaluated. All cardiac dimensions and volumes were adjusted for body surface area (BSA). Left atrium and left ventricle volumes were significantly (P<0.001) larger in elite female handball players compared with sedentary controls. Even right atrium area as well as right ventricular end-diastolic and end-systolic area were significantly (P<0.001) larger in elite female handball players. Significant differences were observed in three out of five systolic parameters. Most diastolic function parameters did not differ between the two groups. The findings from the present study suggest that similar cardiac remodeling takes place in elite female handball players as it does in athletes pursuing endurance or team game sports.

Patient-specific models of cardiac biomechanics

NASA Astrophysics Data System (ADS)

Krishnamurthy, Adarsh; Villongco, Christopher T.; Chuang, Joyce; Frank, Lawrence R.; Nigam, Vishal; Belezzuoli, Ernest; Stark, Paul; Krummen, David E.; Narayan, Sanjiv; Omens, Jeffrey H.; McCulloch, Andrew D.; Kerckhoffs, Roy C. P.

2013-07-01

Patient-specific models of cardiac function have the potential to improve diagnosis and management of heart disease by integrating medical images with heterogeneous clinical measurements subject to constraints imposed by physical first principles and prior experimental knowledge. We describe new methods for creating three-dimensional patient-specific models of ventricular biomechanics in the failing heart. Three-dimensional bi-ventricular geometry is segmented from cardiac CT images at end-diastole from patients with heart failure. Human myofiber and sheet architecture is modeled using eigenvectors computed from diffusion tensor MR images from an isolated, fixed human organ-donor heart and transformed to the patient-specific geometric model using large deformation diffeomorphic mapping. Semi-automated methods were developed for optimizing the passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Material properties of active cardiac muscle contraction were optimized to match ventricular pressures measured by cardiac catheterization, and parameters of a lumped-parameter closed-loop model of the circulation were estimated with a circulatory adaptation algorithm making use of information derived from echocardiography. These components were then integrated to create a multi-scale model of the patient-specific heart. These methods were tested in five heart failure patients from the San Diego Veteran's Affairs Medical Center who gave informed consent. The simulation results showed good agreement with measured echocardiographic and global functional parameters such as ejection fraction and peak cavity pressures.

Cardiac function and perfusion dynamics measured on a beat-by-beat basis in the live mouse using ultra-fast 4D optoacoustic imaging

NASA Astrophysics Data System (ADS)

Ford, Steven J.; Deán-Ben, Xosé L.; Razansky, Daniel

2015-03-01

The fast heart rate (~7 Hz) of the mouse makes cardiac imaging and functional analysis difficult when studying mouse models of cardiovascular disease, and cannot be done truly in real-time and 3D using established imaging modalities. Optoacoustic imaging, on the other hand, provides ultra-fast imaging at up to 50 volumetric frames per second, allowing for acquisition of several frames per mouse cardiac cycle. In this study, we combined a recently-developed 3D optoacoustic imaging array with novel analytical techniques to assess cardiac function and perfusion dynamics of the mouse heart at high, 4D spatiotemporal resolution. In brief, the heart of an anesthetized mouse was imaged over a series of multiple volumetric frames. In another experiment, an intravenous bolus of indocyanine green (ICG) was injected and its distribution was subsequently imaged in the heart. Unique temporal features of the cardiac cycle and ICG distribution profiles were used to segment the heart from background and to assess cardiac function. The 3D nature of the experimental data allowed for determination of cardiac volumes at ~7-8 frames per mouse cardiac cycle, providing important cardiac function parameters (e.g., stroke volume, ejection fraction) on a beat-by-beat basis, which has been previously unachieved by any other cardiac imaging modality. Furthermore, ICG distribution dynamics allowed for the determination of pulmonary transit time and thus additional quantitative measures of cardiovascular function. This work demonstrates the potential for optoacoustic cardiac imaging and is expected to have a major contribution toward future preclinical studies of animal models of cardiovascular health and disease.

Longitudinal changes in late systolic cardiac load and serum NT-proBNP levels in healthy middle-aged Japanese men.

PubMed

Tomiyama, Hirofumi; Nishikimi, Toshio; Matsumoto, Chisa; Kimura, Kazutaka; Odaira, Mari; Shiina, Kazuki; Yamashina, Akira

2015-04-01

We determined whether any significant association exists between change in late systolic cardiac load with time, estimated by radial pressure waveform analysis, and development of cardiac hemodynamic stress in individuals with preserved cardiac function. Brachial-ankle pulse wave velocity, radial augmentation index (rAI), first peak of the radial pressure waveform (SP1), systolic and pulse pressure at the second peak of the radial pressure waveform (SP2 and PP2), and serum levels of N-terminal fragment B-type natriuretic peptide (NT-proBNP) were measured at the start (first examination) and at the end (second examination) of this 3-year study in healthy Japanese men (n = 1,851). A stepwise multivariate linear regression analysis demonstrated that among the parameters of radial pressure waveform analysis and markers of arterial stiffness analyzed, only PP2 was significantly associated with serum NT-proBNP levels in study participants at both the first and second examinations. Furthermore, among the parameters analyzed, only change in PP2 was significantly correlated with the change in serum NT-proBNP levels during the study period (beta = 0.131, P < 0.001). Sustained late systolic cardiac load might be a more significant determinant of the development of cardiac hemodynamic stress than sustained early systolic cardiac load or arterial stiffening in individuals with preserved cardiac function. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The relationship between erythrocyte membrane fatty acid levels and cardiac autonomic function in obese children.

PubMed

Mustafa, Gulgun; Kursat, Fidanci Muzaffer; Ahmet, Tas; Alparslan, Genc Fatih; Omer, Gunes; Sertoglu, Erdem; Erkan, Sarı; Ediz, Yesilkaya; Turker, Turker; Ayhan, Kılıc

Childhood obesity is a worldwide health concern. Studies have shown autonomic dysfunction in obese children. The exact mechanism of this dysfunction is still unknown. The aim of this study was to assess the relationship between erythrocyte membrane fatty acid (EMFA) levels and cardiac autonomic function in obese children using heart rate variability (HRV). A total of 48 obese and 32 healthy children were included in this case-control study. Anthropometric and biochemical data, HRV indices, and EMFA levels in both groups were compared statistically. HRV parameters including standard deviation of normal-to-normal R-R intervals (NN), root mean square of successive differences, the number of pairs of successive NNs that differ by >50 ms (NN50), the proportion of NN50 divided by the total number of NNs, high-frequency power, and low-frequency power were lower in obese children compared to controls, implying parasympathetic impairment. Eicosapentaenoic acid and docosahexaenoic acid levels were lower in the obese group (p<0.001 and p=0.012, respectively). In correlation analysis, in the obese group, body mass index standard deviation and linoleic acid, arachidonic acid, triglycerides, and high-density lipoprotein levels showed a linear correlation with one or more HRV parameter, and age, eicosapentaenoic acid, and systolic and diastolic blood pressure correlated with mean heart rate. In linear regression analysis, age, dihomo-gamma-linolenic acid, linoleic acid, arachidonic acid, body mass index standard deviation, systolic blood pressure, triglycerides, low-density lipoprotein and high-density lipoprotein were related to HRV parameters, implying an effect on cardiac autonomic function. There is impairment of cardiac autonomic function in obese children. It appears that levels of EMFAs such as linoleic acid, arachidonic acid and dihomo-gamma-linolenic acid play a role in the regulation of cardiac autonomic function in obese children. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Aging-related arterial-cardiac interaction in Japanese men.

PubMed

Maruyama, Yoshiaki

2009-11-01

Vascular and cardiac aging is rapidly progressing among the Japanese population. A close relation exists between the artery and cardiac performance (arterial-cardiac interaction), but the relationships between age and these parameters have not been well examined. The aim of this study was to elucidate the changes of arterial-cardiac interaction with aging, using pulse wave velocity (PWV) as an indicator of atherosclerosis. The subjects comprised 595 adult men (mean age, 58.8 +/- 12.2 years) without any history of cardiovascular disease. After correlating PWV, cardiac structure, cardiac function, and blood pressure to age, subjects were divided into five age groups to compare changes in these parameters. Pulse wave velocity exhibited a strong positive correlation with age (r = 0.461, P < 0.01) and increased significantly over 55 years old, and left atrial dimension, relative wall thickness, systolic blood pressure, and pulse pressure correlated positively with age and increased similarly. Left ventricular volume correlated negatively with age and decreased similarly. These parameters significantly correlated with PWV. Aortic diameter (AoD) positively and EA ratio (E/A) negatively exhibited a correlation with age and revealed earlier change before PWV increase. Aortic diameter increased significantly over 45 years old and stayed flat, but E/A decreased linearly from the early period. Diastolic blood pressure (DBP) increased in the early period and decreased over 75 years of age. Agerelated atherosclerotic close arterial-cardiac interaction exists between the vessels and cardiac performance, but AoD, E/A, and DBP change in early age independent of atherosclerosis.

Echocardiographic Assessment of Cardiac Function by Conventional and Speckle-Tracking Echocardiography in Dogs with Patent Ductus Arteriosus.

PubMed

Spalla, I; Locatelli, C; Zanaboni, A M; Brambilla, P; Bussadori, C

2016-05-01

Patent ductus arteriosus (PDA) is one of the most common congenital heart defects in dogs. Advanced echocardiographic techniques such as speckle-tracking echocardiography (STE) have not been extensively used to evaluate cardiac function in affected dogs. Advanced echocardiographic techniques are more sensitive than standard echocardiographic techniques in analyzing systolic function in dogs with PDA. Forty-four client-owned dogs: 34 dogs with PDA (preoperative evaluation) and 10 healthy sex- and weight-matched controls. Prospective study. Dogs were recruited over a 2-year period. Complete echocardiographic evaluation was performed, including conventional (end-diastolic volumes indexed to body surface area in B and M-mode [EDVIB /M ], end-systolic volumes indexed to body surface area in B and M-mode [ESVIB /M ], allometric scaling in diastole and systole [AlloD/S], pulmonary flow to systemic flow [Qp/Qs], ejection fraction [EF] and fractional shortening [FS]) and speckle-tracking echocardiography ([STE]: global longitudinal, radial and circumferential strain [S] and strain rate [SR]). Dogs with PDA had significantly different EDVIB /M , ESVIB /M , AlloD/S, Qp/Qs and all STE-derived parameters (global longitudinal S and SR, global circumferential S and SR, global radial S and SR)compared to healthy dogs. No correlation was found between standard techniques (EDVIB /M , ESVIB /M , AlloD/S, Qp/Qs) and STE-derived parameters (global longitudinal, circumferential and radial S and SR). Conventional parameters routinely used to assess systolic function (EF and FS) were not different between the groups; STE-derived parameters identified subtle changes in cardiac systolic function and contractility between the 2 groups of dogs. Based on these findings, STE may be a more appropriate tool to assess cardiac contractility in dogs with PDA. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Hypothyroidism and the Heart.

PubMed

Udovcic, Maja; Pena, Raul Herrera; Patham, Bhargavi; Tabatabai, Laila; Kansara, Abhishek

2017-01-01

Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility, vascular resistance, blood pressure, and heart rhythm. With this review, we aim to describe the effects of hypothyroidism and subclinical hypothyroidism on the heart. Additionally, we attempt to briefly describe how hypothyroid treatment affects cardiovascular parameters.

Wave intensity analysis in mice: an ultrasound-based study in the abdominal aorta and common carotid artery

NASA Astrophysics Data System (ADS)

Di Lascio, N.; Kusmic, C.; Stea, F.; Faita, F.

2017-03-01

Wave Intensity Analysis (WIA) can provide parameters representative of the interaction between the vascular network and the heart. It has been already demonstrated that WIA-derived biomarkes have a quantitative physiological meaning. Aim of this study was to develop an image process algorithm for performing non-invasive WIA in mice and correlate commonly used cardiac function parameters with WIA-derived indexes. Sixteen wild-type male mice (8 weeks-old) were imaged with high-resolution ultrasound (Vevo 2100). Abdominal aorta and common carotid pulse wave velocities (PWVabd, PWVcar) were obtained processing B-Mode and PW-Doppler images and employed to assess WIA. Amplitudes of the first (W1abd, W1car) and the second (W2abd, W2car) local maxima and minimum (Wbabd,Wbcar) were evaluated; areas under the negative part of the curve were also calculated (NAabd, NAcar). Cardiac output (CO), ejection fraction (EF) fractional shortening (FS) and stroke volume (SV) were estimated; strain analysis provided strain and strain rate values for longitudinal, radial and circumferential directions (LS, LSR, RS, RSR, CS, CSR). Isovolumetric relaxation time (IVRT) was calculated from mitral inflow PW-Doppler images; IVRT values were normalized for cardiac cycle length. W1abd was correlated with LS (R=0.65) and LSR (R=0.59), while W1car was correlated with CO (R=0.58), EF (R=0.72), LS (R=0.65), LSR (R=0.89), CS (R=0.71), CSR (R=0.70). Both W2abd and W2car were not correlated with IVRT. Carotid artery WIA-derived parameters are more representative of cardiac function than those obtained from the abdominal aorta. The described US-based method can provide information about cardiac function and cardio-vascular interaction simply studying a single vascular site.

Childhood obesity and cardiac remodeling: from cardiac structure to myocardial mechanics.

PubMed

Tadic, Marijana; Cuspidi, Cesare

2015-08-01

Epidemic of obesity, especially morbid obesity, among children and adolescents, is a key factor associated with the dramatic increase in prevalence of type 2 diabetes mellitus, arterial hypertension, and metabolic syndrome in this population. Furthermore, childhood obesity represents a very important predictor of obesity in adulthood that is related to cardiovascular and cerebrovascular diseases. Overweight and obesity in children and adolescents are associated with impairment of cardiac structure and function. The majority of studies investigated the influence of obesity on left ventricular remodeling. However, the impact of obesity on the right ventricle, both the atria, and myocardial mechanics has been insufficiently studied. The aim of this review article is to summarize all data about heart remodeling in childhood, from cardiac size, throughout systolic and diastolic function, to myocardial mechanics, using a wide range of mainly echocardiographic techniques and parameters. Additionally, we sought to present current knowledge about the influence of weight loss, achieved by various therapeutic approaches, on the improvement of cardiac geometry, structure, and function in obese children and adolescents.

[Influence of detomidine on echocardiographic function parameters and cardiac hemodynamics in horses with and without heart murmur].

PubMed

Gehlen, H; Kroker, K; Deegen, E; Stadler, P

2004-03-01

30 warmblood horses were examined before and after sedation with 20 micrograms/kg BW detomidine, to determine changes of cardiac function parameters, using B-mode, M-mode and Doppler echocardiography. 15 horses showed a heart murmur, but no clinical signs of cardiac heart failure, 15 horses had neither a heart murmur nor other signs of cardiac disease. After sedation with detomidine we could recognise a significant increase of end-diastolic left atrium diameter, an increase of end-systolic left ventricular diameter and aortic root diameter. The end-systolic thickness of papillary muscle and interventricular septum showed a decrease. Fractional shortening and amplitude of left ventricular wall motion was decreased after sedation. The mitral valve echogram revealed a presystolic valve closure and an inflection in the Ac slope (B-notch) in xy horses before sedation. Both increased after sedation with detomidine. Doppler echocardiography showed a decrease of blood flow velocity and velocity time integral (VTI) in the left and right ventricular outflow tract after sedation. Regurgitant flow signals were intensified following sedation in xy horses, especially at the mitral valve.

Accurate computer-aided quantification of left ventricular parameters: experience in 1555 cardiac magnetic resonance studies from the Framingham Heart Study.

PubMed

Hautvast, Gilion L T F; Salton, Carol J; Chuang, Michael L; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J

2012-05-01

Quantitative analysis of short-axis functional cardiac magnetic resonance images can be performed using automatic contour detection methods. The resulting myocardial contours must be reviewed and possibly corrected, which can be time-consuming, particularly when performed across all cardiac phases. We quantified the impact of manual contour corrections on both analysis time and quantitative measurements obtained from left ventricular short-axis cine images acquired from 1555 participants of the Framingham Heart Study Offspring cohort using computer-aided contour detection methods. The total analysis time for a single case was 7.6 ± 1.7 min for an average of 221 ± 36 myocardial contours per participant. This included 4.8 ± 1.6 min for manual contour correction of 2% of all automatically detected endocardial contours and 8% of all automatically detected epicardial contours. However, the impact of these corrections on global left ventricular parameters was limited, introducing differences of 0.4 ± 4.1 mL for end-diastolic volume, -0.3 ± 2.9 mL for end-systolic volume, 0.7 ± 3.1 mL for stroke volume, and 0.3 ± 1.8% for ejection fraction. We conclude that left ventricular functional parameters can be obtained under 5 min from short-axis functional cardiac magnetic resonance images using automatic contour detection methods. Manual correction more than doubles analysis time, with minimal impact on left ventricular volumes and ejection fraction. Copyright © 2011 Wiley Periodicals, Inc.

Cardiac Function in Young and Old Little Mice

PubMed Central

Reddy, Anilkumar K.; Amador-Noguez, Daniel; Darlington, Gretchen J.; Scholz, Beth A.; Michael, Lloyd H.; Hartley, Craig J.; Entman, Mark L.; Taffet, George E.

2009-01-01

We studied cardiac function in young and old, wild-type (WT), and longer-living Little mice using cardiac flow velocities, echocardiographic measurements, and left ventricular (LV) pressure (P) to determine if enhanced reserves were in part responsible for longevity in these mice. Resting/baseline cardiac function, as measured by velocities, LV dimensions, +dP/dtmax, and −dP/dtmax, was significantly lower in young Little mice versus young WT mice. Fractional shortening (FS) increased significantly, and neither +dP/dtmax nor −dP/dtmax declined with age in Little mice. In contrast, old WT mice had no change in FS but had significantly lower +dP/dtmax and −dP/dtmax versus young WT mice. Significant decreases were observed in the velocity indices of old Little mice versus old WT mice, but other parameters were unchanged. The magnitude of dobutamine stress response remained unchanged with age in Little mice, while that in WT mice decreased. These data suggest that while resting cardiac function in Little mice versus WT mice is lower at young age, it is relatively unaltered with aging. Additionally, cardiac function in response to stress was maintained with age in Little mice but not in their WT counterparts. Thus, some mouse models of increased longevity may not be associated with enhanced reserves. PMID:18166681

Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies

PubMed Central

Thapa, Dharendra; Shepherd, Danielle L.

2014-01-01

Cardiac tissue contains discrete pools of mitochondria that are characterized by their subcellular spatial arrangement. Subsarcolemmal mitochondria (SSM) exist below the cell membrane, interfibrillar mitochondria (IFM) reside in rows between the myofibrils, and perinuclear mitochondria are situated at the nuclear poles. Microstructural imaging of heart tissue coupled with the development of differential isolation techniques designed to sequentially separate spatially distinct mitochondrial subpopulations have revealed differences in morphological features including shape, absolute size, and internal cristae arrangement. These findings have been complemented by functional studies indicating differences in biochemical parameters and, potentially, functional roles for the ATP generated, based upon subcellular location. Consequently, mitochondrial subpopulations appear to be influenced differently during cardiac pathologies including ischemia/reperfusion, heart failure, aging, exercise, and diabetes mellitus. These influences may be the result of specific structural and functional disparities between mitochondrial subpopulations such that the stress elicited by a given cardiac insult differentially impacts subcellular locales and the mitochondria contained within. The goal of this review is to highlight some of the inherent structural and functional differences that exist between spatially distinct cardiac mitochondrial subpopulations as well as provide an overview of the differential impact of various cardiac pathologies on spatially distinct mitochondrial subpopulations. As an outcome, we will instill a basis for incorporating subcellular spatial location when evaluating the impact of cardiac pathologies on the mitochondrion. Incorporation of subcellular spatial location may offer the greatest potential for delineating the influence of cardiac pathology on this critical organelle. PMID:24778166

Excessive training induces molecular signs of pathologic cardiac hypertrophy.

PubMed

da Rocha, Alisson L; Teixeira, Giovana R; Pinto, Ana P; de Morais, Gustavo P; Oliveira, Luciana da C; de Vicente, Larissa Gaioto; da Silva, Lilian E C M; Pauli, José R; Cintra, Dennys E; Ropelle, Eduardo R; de Moura, Leandro P; Mekary, Rania A; de Freitas, Ellen C; da Silva, Adelino S R

2018-05-24

Chronic exercise induces cardiac remodeling that promotes left ventricular hypertrophy and cardiac functional improvement, which are mediated by the mammalian or the mechanistic target of rapamycin (mTOR) as well as by the androgen and glucocorticoid receptors (GRs). However, pathological conditions (i.e., chronic heart failure, hypertension, and aortic stenosis, etc.) also induce cardiac hypertrophy, but with detrimental function, high levels of proinflammatory cytokines and myostatin, elevated fibrosis, reduced adenosine monophosphate-activated protein kinase (AMPK) activation, and fetal gene reactivation. Furthermore, recent studies have evidenced that excessive training induced an inflammatory status in the serum, muscle, hypothalamus, and liver, suggesting a pathological condition that could also be detrimental to cardiac tissue. Here, we verified the effects of three running overtraining (OT) models on the molecular parameters related to physiological and pathological cardiac hypertrophy. C57BL/6 mice performed three different OT protocols and were evaluated for molecular parameters related to physiological and pathological cardiac hypertrophy, including immunoblotting, reverse transcription polymerase chain reaction, histology, and immunohistochemistry analyses. In summary, the three OT protocols induced left ventricle (LV) hypertrophy with signs of cardiac fibrosis and negative morphological adaptations. These maladaptations were accompanied by reductions in AMPKalpha (Thr172) phosphorylation, androgen receptor, and GR expressions, as well as by an increase in interleukin-6 expression. Specifically, the downhill running-based OT model reduced the content of some proteins related to the mTOR signaling pathway and upregulated the β-isoform of myosin heavy-chain gene expression, presenting signs of LV pathological hypertrophy development. © 2018 Wiley Periodicals, Inc.

Heart rate variability and heart rate turbulence in patients with polycystic ovary syndrome.

PubMed

Özkeçeci, Gülay; Ünlü, Bekir Serdar; Dursun, Hüseyin; Akçi, Önder; Köken, Gülengül; Onrat, Ersel; Avşar, Alaettin

2016-05-01

Cardiac autonomic dysfunction may develop in patients with polycystic ovary syndrome (PCOS). Heart rate variability (HRV) and heart rate turbulence (HRT) are used in assessing cardiac autonomic functions. The goal of this study was to compare the cardiac autonomic functions in patients with PCOS and healthy controls. To our knowledge, this is the first study evaluating cardiac autonomic functions in patients with PCOS with respect to both HRV and HRT. Twenty-three patients with PCOS (mean age 22.8±3.9 years) and 25 healthy female volunteers who were matched for age and body mass index (BMI) (mean age 23.5±6.2 years) were enrolled in this as case-control study. Twenty-four hour ambulatory electrocardiogram recordings of all participants were taken using Pathfinder software. The time domain parameters of HRV and HRT, including turbulence onset (TO) and turbulence slope, were calculated. Diagnosis of PCOS was made with physical and laboratory findings of hirsutism or biochemical hyperandrogenism and chronic anovulation. Diabetes mellitus, other hormon disorders or hormon therapy, pregnancy, atrial fibrilation, obesite, chronic diseases, disorders of the autonomic nervous system, a history of drug use affecting the autonomic nervous system were excluded. There were no significant differences in HRV and HRT parameters between the two groups. Cardiovascular risk factors, such as BMI, blood pressure, fasting blood glucose, and lipid parameters, were also similar. Triangular index measure of HRV was negatively correlated with high density lipoprotein cholesterol levels (r=-0.47, p<0.05), while age and BMI were significantly correlated with TO (r=0.31 and 0.47, respectively; p<0.05 for all). Cardiac autonomic functions were not found to be altered in patients with PCOS in comparison with healthy controls. These results may be explained with the absence of concomitant cardiovascular risk factors with the patients being in the early stage of the disease.

The diastolic function to cyclic variation of myocardial ultrasonic backscatter relation: the influence of parameterized diastolic filling (PDF) formalism determined chamber properties.

PubMed

Lloyd, Christopher W; Shmuylovich, Leonid; Holland, Mark R; Miller, James G; Kovács, Sándor J

2011-08-01

Myocardial tissue characterization represents an extension of currently available echocardiographic imaging. The systematic variation of backscattered energy during the cardiac cycle (the "cyclic variation" of backscatter) has been employed to characterize cardiac function in a wide range of investigations. However, the mechanisms responsible for observed cyclic variation remain incompletely understood. As a step toward determining the features of cardiac structure and function that are responsible for the observed cyclic variation, the present study makes use of a kinematic approach of diastolic function quantitation to identify diastolic function determinants that influence the magnitude and timing of cyclic variation. Echocardiographic measurements of 32 subjects provided data for determination of the cyclic variation of backscatter to diastolic function relation characterized in terms of E-wave determined, kinematic model-based parameters of chamber stiffness, viscosity/relaxation and load. The normalized time delay of cyclic variation appears to be related to the relative viscoelasticity of the chamber and predictive of the kinematic filling dynamics as determined using the parameterized diastolic filling formalism (with r-values ranging from .44 to .59). The magnitude of cyclic variation does not appear to be strongly related to the kinematic parameters. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Acid-base balance and cardiac index in SO2-bronchitic, papaine-emphysematous and paraquat-fibrotic rats after isoproterenol treatment.

PubMed

Vértes, K; Debreczeni, L A

1990-01-01

SO2-bronchitis, papaine-emphysema and paraquat fibrosis were induced in Wistar rats. Blood pressure, cardiac index, total peripheral resistance, arterial blood gas values, parameters of acid-base balance were determined. Effects of 0.1 and 0.3 microgram.-1.min-1 isoproterenol iv. infusion were examined. Morphologic alterations of the lungs were verified by histopathological examinations. All the parameters investigated were found to be normal in the control rats. The treated groups differed from the normal ones: an increased blood pressure was observed in emphysema and fibrosis. A decreased cardiac index was characteristic of chronic bronchitis, high cardiac index of emphysema, high TPR of bronchitis and arterial hypoxaemy of fibrosis. The groups reacted differently to beta adrenergic stimulation: in bronchitic and fibrotic rats the cardiac index was augmented, whereas in emphysematous ones the increase proved to be smaller. The effects of isoproterenol infusion can be related to the altered beta-receptor function in the various experimental pulmonary diseases.

Hypothyroidism and the Heart

PubMed Central

Udovcic, Maja; Pena, Raul Herrera; Patham, Bhargavi; Tabatabai, Laila; Kansara, Abhishek

2017-01-01

Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility, vascular resistance, blood pressure, and heart rhythm. With this review, we aim to describe the effects of hypothyroidism and subclinical hypothyroidism on the heart. Additionally, we attempt to briefly describe how hypothyroid treatment affects cardiovascular parameters. PMID:28740582

Extreme respiratory sinus arrhythmia enables overwintering black bear survival--physiological insights and applications to human medicine.

PubMed

Laske, Timothy G; Harlow, Henry J; Garshelis, David L; Iaizzo, Paul A

2010-10-01

American black bears survive winter months without food and water while in a mildly hypothermic, hypometabolic, and inactive state, yet they appear to be able to return to near-normal systemic function within minutes of arousal. This study's goal was to characterize the cardiovascular performance of overwintering black bears and elicit the underlying mechanisms enabling survival. Mid-winter cardiac electrophysiology was assessed in four wild black bears using implanted data recorders. Paired data from early and late winter were collected from 37 wild bears, which were anesthetized and temporarily removed from their dens to record cardiac electrophysiological parameters (12-lead electrocardiograms) and cardiac dimensional changes (echocardiography). Left ventricular thickness, primary cardiac electrophysiological parameters, and cardiovascular response to threats ("fight or flight" response) were preserved throughout winter. Dramatic respiratory sinus arrhythmias were recorded (cardiac cycle length variations up to 865%) with long sinus pauses between breaths (up to 13 s). The accelerated heart rate during breathing efficiently transports oxygen, with the heart "resting" between breaths to minimize energy usage. This adaptive cardiac physiology may have broad implications for human medicine.

Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin-resistant rats

PubMed Central

Apaijai, Nattayaporn; Pintana, Hiranya; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2013-01-01

Background and Purpose Long-term high-fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors, vildagliptin and sitagliptin, are oral anti-diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance. Experimental Approach Male Wistar rats weighing 180–200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg−1·day−1), sitagliptin (30 mg·kg−1·day−1) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined. Key Results Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high-density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV. Conclusions and Implications Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin-resistant rats. PMID:23488656

[Effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome].

PubMed

Li, Lei; Lin, Cheng-Ren; Ren, Jian-Xun; Miao, Lan; Yao, Ming-Jiang; Li, Dan; Shi, Yue; Ma, Yan-Lei; Fu, Jian-Hua; Liu, Jian-Xun

2014-02-01

To evaluate that the effect of formula of removing both phlegm and blood stasis in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. Totally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Danlou tablet group, and Tanyu Tonzhi Fang(TYTZ) groups with doses of 2. 0, 1. 0 and 0. 5 g kg-1, with six in each group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary heart disease model of phlegm-stasis cementation syndrome. After the operation, they were administered with drugs for 8 weeks. The changes in the myocardial ischemia were observed. The changes in the cardiac function and structure were detected by cardiac ultrasound and noninvasive hemodynamic method. Compared with the normal control group, the model group showed significant increase in myocardial ischemia and SVR and obvious decrease in CO, SV and LCW in noninvasive hemodynamic parameters (P <0.05 or P <0.01). The ultrasonic cardiogram indicated notable decrease in IVSd, LVPWs, EF and FS, and remarkable increase in LVIDs (P<0. 05 orP<0.01). Compared with the model group, TYTZ could reduce the myocardial ischemia, strengthen cardiac function, and improve the abnormal cardiac structure and function induced by ischemia (P <0. 05 or P <0. 01). TYTZ shows a significant effect in improving cardiac function of Chinese mini-swine with coronary heart disease of phlegm-stasis cementation syndrome. The clinical cardiac function detection method could be adopted to correctly evaluate the changes in the post-myocardial ischemia cardiac function, and narrow the gap between clinical application and basic experimental studies.

Cardiac adaption during pregnancy in women with congenital heart disease and healthy women.

PubMed

Kampman, Marlies A M; Valente, Mattia A E; van Melle, Joost P; Balci, Ali; Roos-Hesselink, Jolien W; Mulder, Barbara J M; van Dijk, A P J; Oudijk, M A; Jongbloed, M R M; van Veldhuisen, Dirk J; Pieper, Petronella G

2016-08-15

Pregnancy in women with congenital heart disease (CHD) is associated with deterioration in cardiac function. However, longitudinal data are scarce. This study describes serial changes in cardiac dimensions and function during pregnancy in women with CHD and compares these with healthy pregnant women (controls). Eight tertiary centres prospectively enrolled 125 pregnant women with CHD (pregnancy duration <20 weeks). Controls (N=49) were recruited from low-risk midwife practices. Standardised echocardiography at 20 and 32 weeks gestation and 1 year postpartum was performed. Age and parity were comparable between both groups (p>0.1). Left ventricular ejection fraction (LVEF) <45% was present in 3.2% of women with CHD and 14.4% had tricuspid annular plane systolic excursion (TAPSE) <16 mm. Absolute values of ventricular function parameters and diameters were less favourable in women with CHD. No permanent changes occurred in right and left ventricular function parameters and dimensions in women with CHD. The patterns of change in cardiac function and dimensions were comparable between women with CHD and controls, except for LVEF (p=0.026). In women with right-sided CHD the pattern of TAPSE over time differed from controls (p=0.043) (no decrease in TAPSE postpregnancy in CHD). In women with left-sided CHD left ventricular end-diastolic diameter (LVEDD) tended to increase compared with controls (p=0.045). Absolute levels of ventricular function parameters and diameters differ between CHD and controls, but changes during and after pregnancy are generally comparable. However, different patterns over time seen for TAPSE and LVEDD in women with right-sided and left-sided CHD, respectively, compared with controls indicate the importance of echocardiographic follow-up during pregnancy in women with CHD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A New Parameter for Cardiac Efficiency Analysis

NASA Astrophysics Data System (ADS)

Borazjani, Iman; Rajan, Navaneetha Krishnan; Song, Zeying; Hoffmann, Kenneth; MacMahon, Eileen; Belohlavek, Marek

2014-11-01

Detecting and evaluating a heart with suboptimal pumping efficiency is a significant clinical goal. However, the routine parameters such as ejection fraction, quantified with current non-invasive techniques are not predictive of heart disease prognosis. Furthermore, they only represent left-ventricular (LV) ejection function and not the efficiency, which might be affected before apparent changes in the function. We propose a new parameter, called the hemodynamic efficiency (H-efficiency) and defined as the ratio of the useful to total power, for cardiac efficiency analysis. Our results indicate that the change in the shape/motion of the LV will change the pumping efficiency of the LV even if the ejection fraction is kept constant at 55% (normal value), i.e., H-efficiency can be used for suboptimal cardiac performance diagnosis. To apply H-efficiency on a patient-specific basis, we are developing a system that combines echocardiography (echo) and computational fluid dynamics (CFD) to provide the 3D pressure and velocity field to directly calculate the H-efficiency parameter. Because the method is based on clinically used 2D echo, which has faster acquisition time and lower cost relative to other imaging techniques, it can have a significant impact on a large number of patients. This work is partly supported by the American Heart Association.

Adaptive servo ventilation improves cardiac dysfunction and prognosis in chronic heart failure patients with Cheyne-Stokes respiration.

PubMed

Yoshihisa, Akiomi; Shimizu, Takeshi; Owada, Takashi; Nakamura, Yuichi; Iwaya, Shoji; Yamauchi, Hiroyuki; Miyata, Makiko; Hoshino, Yasuto; Sato, Takamasa; Suzuki, Satoshi; Sugimoto, Koichi; Yamaki, Takayoshi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

2011-01-01

Cheyne-Stokes respiration (CSR) is often observed in patients with chronic heart failure (CHF). Although adaptive servo ventilation (ASV) is effective for CSR, it remains unclear whether ASV improves the cardiac function and prognosis of patients with CHF and CSR.Sixty patients with CHF and CSR (mean left ventricular ejection fraction 38.7%, mean apnea hypopnea index 36.8 times/hour, mean central apnea index 19.1 times/hour) were enrolled in this study. Patients were divided into two groups: 23 patients treated with ASV (ASV group) and 37 patients treated without ASV (Non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels and echocardiography were performed before, 3 and 6 months after treatments in each group. Patients were followed-up for cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, NYHA functional class, BNP levels, cardiac systolic and diastolic function were significantly improved with ASV treatment for 6 months. In contrast, none of these parameters changed in the Non-ASV group. Importantly, Kaplan-Meier analysis clearly demonstrated that the event-free rate was significantly higher in the ASV group than in the Non-ASV group.Adaptive servo ventilation improves cardiac function and prognosis in patients with chronic heart failure and Cheyne-Stokes respiration.

Time Course of Atrophic Remodeling: Effects of Exercise on Cardiac Morpology and Function

NASA Technical Reports Server (NTRS)

Scott, J. M.; Martin, D.; Caine, T.; Matz, T.; Ploutz-Snyder, L. L.

2014-01-01

Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. Exercise training is one intervention that has been shown to confer favorable improvements in LV mass and function during unloading. However, the format and intensity of exercise required to induce optimal cardiac improvements has not been investigated. PURPOSE: This randomized, controlled trial was designed to 1) comprehensively characterize the time course of unloading-induced morpho-functional remodeling, and 2) examine the effects of high intensity exercise training on cardiac structural and functional parameters during unloading. METHODS: Twenty six subjects completed 70 days of head down tilt bed rest (HDBR): 17 were randomized to exercise training (ExBR) and 9 remained sedentary. Exercise consisted of integrated high intensity, continuous, and resistance exercise. We assessed cardiac morphology (left ventricular mass; LVM) and function (speckle-tracking assessment of longitudinal, radial, and circumferential strain and twist) before (BR-2), during (BR7,21,31,70), and following (BR+0, +3) HDBR. Cardiorespiratory fitness (VO2max) was evaluated before (BR- 3), during (BR4,25,46,68) and following (BR+0) HDBR. RESULTS: Sedentary HDBR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain, and an increase in twist. ExBR mitigated decreases in LVM and function. Change in twist was significantly related to change in VO2max (R=0.68, p<0.01). CONCLUSIONS: Alterations in cardiac morphology and function begin early during unloading. High-intensity exercise attenuates atrophic morphological and functional remodeling.

Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature.

PubMed

Maagaard, Marie; Heiberg, Johan

2016-09-01

Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3-168 patients, mean age-ranges of 5-33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22-34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O 2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac function should be integrated in the clinical assessment of patients with PE.

Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature

PubMed Central

Heiberg, Johan

2016-01-01

Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3–168 patients, mean age-ranges of 5–33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22–34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac function should be integrated in the clinical assessment of patients with PE. PMID:27747182

Arterial stiffness parameters associated with vitamin D deficiency and supplementation in patients with normal cardiac functions.

PubMed

Sünbül, Murat; Çinçin, Altuğ; Bozbay, Mehmet; Mammadov, Ceyhun; Ataş, Halil; Özşenel, Ekmel Burak; Sarı, İbrahim; Başaran, Yelda

2016-06-01

Arterial stiffness parameters including pulse wave velocity (PWV) and augmentation index (AIx) are associated with increased risk of cardiovascular disease. A close relationship has been demonstrated between vitamin D deficiency and cardiovascular disease. The aim of the present study was to investigate effects of vitamin D deficiency and supplementation on arterial stiffness parameters in patients with normal cardiac functions. Study population consisted of 45 patients with vitamin D deficiency and normal cardiac functions. Median age (interquartile range) was 45.0 (12.00) years, and 33 patients were female. Patients were treated with oral administration of vitamin D3. Arterial stiffness parameters were evaluated using Mobil-O-Graph arteriograph system, which detected signals from the brachial artery before and after treatment. Vitamin D levels significantly increased after treatment (9.0 [6.00] nmol/L vs 29.0 [11.50] nmol/L, p<0.001). No significant difference was observed among conventional echocardiographic parameters before or after treatment. Post-treatment PVW and AIx were significantly lower than baseline measurements (6.8 [1.55] m/s vs 6.4 [1.30] m/s, p<0.001 and 23.0 [22.00]% vs 31.0 [14.50]%, p<0.001, respectively). Baseline vitamin D levels significantly correlated with PWV (r=-0.352, p=0.018). Post-treatment vitamin D levels also significantly correlated with post-treatment PWV (r=-0.442, p=0.002) and AIx (r=-0.419, p=0.004). Multivariate linear regression analysis revealed no independent predictor of baseline log-transformed PWV. Vitamin D supplementation has beneficial effects on arterial stiffness. Arterial stiffness parameters may aid in the assessment of cardiovascular risk in patients with vitamin D deficiency.

Functional screening identifies miRNAs inducing cardiac regeneration.

PubMed

Eulalio, Ana; Mano, Miguel; Dal Ferro, Matteo; Zentilin, Lorena; Sinagra, Gianfranco; Zacchigna, Serena; Giacca, Mauro

2012-12-20

In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.

Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats

PubMed Central

Lee, Young Sook; Choi, Joung-Woo; Oh, Jung-Eun; Yun, Chae-Ok; Kim, Sung Wan

2017-01-01

In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM. PMID:27174688

Sex Differences in the Relation of Body Composition to Cardiovascular Parameters and Functions in Korean Adolescents: A School-Based Study

PubMed Central

Song, Young-Hwan; Kim, Hae Soon; Park, Hae Sook; Jung, Jo Won; Kim, Nam Su; Noh, Chung Il; Hong, Young Mi

2014-01-01

Objective Obesity in adolescence is associated with increased cardiovascular risk. The patterns of obesity and body composition differ between boys and girls. It is uncertain how body composition correlates with the cardiovascular system and whether such correlations differ by sex in adolescents. Methods Body composition (fat-free mass (FFM), adipose mass, waist circumference (WC)) and cardiovascular parameters and functions were studied in 676 healthy Korean adolescents aged 12-16 years. Partial correlation and path analyses were done. Results WC correlated with stroke volume (SV) and cardiac output (CO), systolic blood pressure (SBP) and pulse pressure (PP), cardiac diastolic function (ratio of early to late filling velocity (E/A ratio)), and vascular function (pulse wave velocity (PWV)) in boys. Adipose mass was related to SV, CO, SBP, PP, left ventricular mass (LVM), and PWV in girls – and to E/A ratio in both sexes. FFM affected SV, CO, SBP, and PP in both sexes and LVM in boys. Cardiac systolic functions had no relation with any body composition variable in either sex. Conclusion In adolescence, the interdependence of the cardiovascular system and the body composition differs between sexes. Understanding of those relations is required to control adolescent obesity and prevent adult cardiovascular disease. PMID:24820977

Cardiac function and exercise adaptation in 8 children with LPIN1 mutations.

PubMed

Legendre, Antoine; Khraiche, Diala; Ou, Phalla; Mauvais, François-Xavier; Madrange, Marine; Guemann, Anne-Sophie; Jais, Jean-Philippe; Bonnet, Damien; Hamel, Yamina; de Lonlay, Pascale

2018-03-01

Lipin-1 deficiency is a major cause of rhabdomyolysis that are precipitated by febrile illness. The prognosis is poor, with one-third of patients dying from cardiac arrest during a crisis episode. Apart from acute rhabdomyolysis, most patients are healthy, showing normal clinical and cardiac ultrasound parameters. We report cardiac and exercise examinations of 8 children carrying two LPIN1 mutations. The examinations were performed outside of a myolysis episode, but one patient presented with fever during one examination. All but one patient displayed normal resting cardiac function, as determined by echocardiography. One patient exhibited slight left ventricular dysfunction at rest and a lack of increased stroke volume during cycle ramp exercise. During exercise, peripheral muscle adaptation was impaired in 2 patients compared to healthy controls: they presented an abnormal increase in cardiac output relative to oxygen uptake: dQ/dVO 2 =8.2 and 9.5 (>2DS of controls population). One patient underwent 2 exercise tests; during one test, the patient was febrile, leading to acute rhabdomyolysis in the following hours. He exhibited changes in recovery muscle reoxygenation parameters and an increased dQ/dVO 2 during exercise compared with that under normothermia (7.9 vs 6), which did not lead to acute rhabdomyolysis. The four patients assessed by cardiac 1 H-magnetic resonance spectroscopy exhibited signs of intracardiac steatosis. We observed abnormal haemodynamic profiles during exercise in 3/8 patients with lipin-1 deficiency, suggesting impaired muscle oxidative phosphorylation during exercise. Fever appeared to be an aggravating factor. One patient exhibited moderate cardiac dysfunction, which was possibly related to intracardiac stored lipid toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Right ventricular dysfunction in the R6/2 transgenic mouse model of Huntington's disease is unmasked by dobutamine.

PubMed

Buonincontri, Guido; Wood, Nigel I; Puttick, Simon G; Ward, Alex O; Carpenter, T Adrian; Sawiak, Stephen J; Morton, A Jennifer

2014-01-01

Increasingly, evidence from studies in both animal models and patients suggests that cardiovascular dysfunction is important in HD. Previous studies measuring function of the left ventricle (LV) in the R6/2 model have found a clear cardiac abnormality, albeit with preserved LV systolic function. It was hypothesized that an impairment of RV function might play a role in this condition via mechanisms of ventricular interdependence. To investigate RV function in the R6/2 mouse model of Huntington's disease (HD). Cardiac cine-magnetic resonance imaging (MRI) was used to determine functional parameters in R6/2 mice. In a first experiment, these parameters were derived longitudinally to determine deterioration of cardiac function with disease progression. A second experiment compared the response to a stress test (using dobutamine) of wildtype and early-symptomatic R6/2 mice. There was progressive deterioration of RV systolic function with age in R6/2 mice. Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction in R6/2 mice before any overt symptoms of the disease were apparent. This work adds to accumulating evidence of cardiovascular dysfunction in R6/2 mice, describing for the first time the involvement of the right ventricle. Cardiovascular dysfunction should be considered, both when treatment strategies are being designed, and when searching for biomarkers for HD.

Cardiac regulation in the socially monogamous prairie vole

PubMed Central

Grippo, Angela J.; Lamb, Damon G.; Carter, C. Sue; Porges, Stephen W.

2007-01-01

Social experiences, both positive and negative, may influence cardiovascular regulation. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form social bonds similar to those seen in primates, and this species may provide a useful model for investigating neural and social regulation of cardiac function. Cardiac regulation has not been studied previously in the prairie vole. Radiotelemetry transmitters were implanted into adult female prairie voles under anesthesia, and electrocardiographic parameters were recorded. Autonomic blockade was performed using atenolol (8 mg/kg ip) and atropine methyl nitrate (4 mg/kg ip). Several variables were evaluated, including heart rate (HR), HR variability and the amplitude of respiratory sinus arrhythmia. Sympathetic blockade significantly reduced HR. Parasympathetic blockade significantly increased HR, and reduced HR variability and the amplitude of respiratory sinus arrhythmia. Combined autonomic blockade significantly increased HR, and reduced HR variability and respiratory sinus arrhythmia amplitude. The data indicate that autonomic function in prairie voles shares similarities with primates, with a predominant vagal influence on cardiac regulation. The current results provide a foundation for studying neural and social regulation of cardiac function during different behavioral states in this socially monogamous rodent model. PMID:17107695

Multiphysics and multiscale modelling, data-model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics.

PubMed

Chabiniok, Radomir; Wang, Vicky Y; Hadjicharalambous, Myrianthi; Asner, Liya; Lee, Jack; Sermesant, Maxime; Kuhl, Ellen; Young, Alistair A; Moireau, Philippe; Nash, Martyn P; Chapelle, Dominique; Nordsletten, David A

2016-04-06

With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling.

Autonomic Cardiovascular Control and Executive Function in Chronic Hypotension.

PubMed

Duschek, Stefan; Hoffmann, Alexandra; Reyes Del Paso, Gustavo A; Ettinger, Ulrich

2017-06-01

Chronic low blood pressure (hypotension) is characterized by complaints such as fatigue, reduced drive, dizziness, and cold limbs. Additionally, deficits in attention and memory have been observed. Autonomic dysregulation is considered to be involved in the origin of this condition. The study explored autonomic cardiovascular control in the context of higher cognitive processing (executive function) in hypotension. Hemodynamic recordings were performed in 40 hypotensive and 40 normotensive participants during execution of four classical executive function tasks (number-letter task, n-back task, continuous performance test, and flanker task). Parameters of cardiac sympathetic control, i.e., stroke volume, cardiac output, pre-ejection period, total peripheral resistance, and parasympathetic control, i.e., respiratory sinus arrhythmia and baroreflex sensitivity, were obtained. The hypotensive group exhibited lower stroke volume and cardiac output, as well as higher pre-ejection period and baroreflex sensitivity during task execution. Increased error rates in hypotensive individuals were observed in the n-back and flanker tasks. In the total sample, there were positive correlations of error rates with pre-ejection period, baroreflex sensitivity and respiratory sinus arrhythmia, and negative correlations with cardiac output. Group differences in stroke volume, cardiac output, and pre-ejection period suggest diminished beta-adrenergic myocardial drive during executive function processing in hypotension, in addition to increased baroreflex function. Although further research is warranted to quantify the extent of executive function impairment in hypotension, the results from correlation analysis add evidence to the notion that higher sympathetic inotropic influences and reduced parasympathetic cardiac influences are accompanied by better cognitive performance.

Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment.

PubMed

Lyra-Leite, Davi M; Andres, Allen M; Petersen, Andrew P; Ariyasinghe, Nethika R; Cho, Nathan; Lee, Jezell A; Gottlieb, Roberta A; McCain, Megan L

2017-10-01

Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease. NEW & NOTEWORTHY A new methodology has been developed to measure O 2 consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix elasticity regulates basal mitochondrial function, whereas both matrix elasticity and tissue alignment regulate mitochondrial stress responses. Copyright © 2017 the American Physiological Society.

Effects of obstructive sleep apnea on hemodynamic parameters in patients entering cardiac rehabilitation.

PubMed

Hargens, Trent A; Aron, Adrian; Newsome, Laura J; Austin, Joseph L; Shafer, Brooke M

2015-01-01

Obstructive sleep apnea (OSA) is a prevalent form of sleep-disordered breathing. Evidence suggests that OSA may lead to cardiac remodeling, although the literature is equivocal. Previous literature suggests a high percentage of individuals entering a cardiac rehabilitation (CR) program also have OSA. The objective of this study was to determine whether resting hemodynamic variables were altered in OSA subjects entering CR compared with those without OSA, as determined by impedance cardiography. Subjects entering an early outpatient CR program were screened for OSA using an at-home screening device and verified by a sleep physician. Subjects were divided into an OSA group (n = 48) or a control group (n = 25) on the basis of the screening results. Hemodynamic variables were measured during supine rest using impedance cardiography. A 6-minute walk test was performed to assess functional capacity. The proportion of cardiac diagnoses was similar between groups. Overall, 66% of the subjects were positive for OSA. Subject groups did not differ by age, body mass index, heart rate, diastolic blood pressure, or functional capacity. Cardiac output, cardiac index, stroke volume, contractility index, and left cardiac work index were all significantly decreased in the OSA group compared with the control group (P < .05). Findings suggest that OSA results in decreased cardiac function in patients entering CR, likely because of pressure and volume changes associated with apneic events. This may place those individuals at a disadvantage in recovering from their cardiac event, and place them at increased risk for secondary complications.

Safety of capsule endoscopy using human body communication in patients with cardiac devices.

PubMed

Chung, Joo Won; Hwang, Hye Jin; Chung, Moon Jae; Park, Jeong Youp; Pak, Hui-Nam; Song, Si Young

2012-06-01

The MiroCam (IntroMedic, Ltd., Seoul, Korea) is a small-bowel capsule endoscope that uses human body communication to transmit data. The potential interactions between cardiac devices and the capsule endoscope are causes for concern, but no data are available for this matter. This clinical study was designed to evaluate the potential influence of the MiroCam capsules on cardiac devices. Patients with cardiac pacemakers or implantable cardiac defibrillators referred for evaluation of small bowel disease were prospectively enrolled in this study. Before capsule endoscopy, a cardiologist checked baseline electrocardiograms and functions of the cardiac devices. Cardiac rhythms were continuously monitored by 24-h telemetry during capsule endoscopy in the hospital. After completion of procedures, functions of the cardiac devices were checked again for interference. Images from the capsule endoscopy were reviewed and analyzed for technical problems. Six patients, three with pacemakers and three with implantable cardiac defibrillators, were included in the study. We identified no disturbances in the cardiac devices and no arrhythmias detected on telemetry monitoring during capsule endoscopy. No significant changes in the programmed parameters of the cardiac devices were noted after capsule endoscopy. There were no imaging disturbances from the cardiac devices on capsule endoscopy. Capsule endoscopy using human body communication to transmit data was safely performed in patients with cardiac pacemakers or implantable cardiac defibrillators. Images from the capsule endoscopy were not affected by cardiac devices. A further large-scale study is required to confirm the safety of capsule endoscopy with various types of cardiac devices.

Erroneous cardiac ECG-gated PET list-mode trigger events can be retrospectively identified and replaced by an offline reprocessing approach: first results in rodents

NASA Astrophysics Data System (ADS)

Böning, Guido; Todica, Andrei; Vai, Alessandro; Lehner, Sebastian; Xiong, Guoming; Mille, Erik; Ilhan, Harun; la Fougère, Christian; Bartenstein, Peter; Hacker, Marcus

2013-11-01

The assessment of left ventricular function, wall motion and myocardial viability using electrocardiogram (ECG)-gated [18F]-FDG positron emission tomography (PET) is widely accepted in human and in preclinical small animal studies. The nonterminal and noninvasive approach permits repeated in vivo evaluations of the same animal, facilitating the assessment of temporal changes in disease or therapy response. Although well established, gated small animal PET studies can contain erroneous gating information, which may yield to blurred images and false estimation of functional parameters. In this work, we present quantitative and visual quality control (QC) methods to evaluate the accuracy of trigger events in PET list-mode and physiological data. Left ventricular functional analysis is performed to quantify the effect of gating errors on the end-systolic and end-diastolic volumes, and on the ejection fraction (EF). We aim to recover the cardiac functional parameters by the application of the commonly established heart rate filter approach using fixed ranges based on a standardized population. In addition, we propose a fully reprocessing approach which retrospectively replaces the gating information of the PET list-mode file with appropriate list-mode decoding and encoding software. The signal of a simultaneously acquired ECG is processed using standard MATLAB vector functions, which can be individually adapted to reliably detect the R-peaks. Finally, the new trigger events are inserted into the PET list-mode file. A population of 30 mice with various health statuses was analyzed and standard cardiac parameters such as mean heart rate (119 ms ± 11.8 ms) and mean heart rate variability (1.7 ms ± 3.4 ms) derived. These standard parameter ranges were taken into account in the QC methods to select a group of nine optimal gated and a group of eight sub-optimal gated [18F]-FDG PET scans of mice from our archive. From the list-mode files of the optimal gated group, we randomly deleted various fractions (5% to 60%) of contained trigger events to generate a corrupted group. The filter approach was capable to correct the corrupted group and yield functional parameters with no significant difference to the optimal gated group. We successfully demonstrated the potential of the fully reprocessing approach by applying it to the sub-optimal group, where the functional parameters were significantly improved after reprocessing (mean EF from 41% ± 16% to 60% ± 13%). When applied to the optimal gated group the fully reprocessing approach did not alter the functional parameters significantly (mean EF from 64% ± 8% to 64 ± 7%). This work presents methods to determine and quantify erroneous gating in small animal gated [18F]-FDG PET scans. We demonstrate the importance of a quality check for cardiac triggering contained in PET list-mode data and the benefit of optionally reprocessing the fully recorded physiological information to retrospectively modify or fully replace the cardiac triggering in PET list-mode data. We aim to provide a preliminary guideline of how to proceed in the presence of errors and demonstrate that offline reprocessing by filtering erroneous trigger events and retrospective gating by ECG processing is feasible. Future work will focus on the extension by additional QC methods, which may exploit the amplitude of trigger events and ECG signal by means of pattern recognition. Furthermore, we aim to transfer the proposed QC methods and the fully reprocessing approach to human myocardial PET/CT.

Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure.

PubMed

Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

2014-12-01

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.

Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure

PubMed Central

Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

2014-01-01

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 1013 vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 1012 vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure–volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF. PMID:25023328

An automatic method to calculate heart rate from zebrafish larval cardiac videos.

PubMed

Kang, Chia-Pin; Tu, Hung-Chi; Fu, Tzu-Fun; Wu, Jhe-Ming; Chu, Po-Hsun; Chang, Darby Tien-Hao

2018-05-09

Zebrafish is a widely used model organism for studying heart development and cardiac-related pathogenesis. With the ability of surviving without a functional circulation at larval stages, strong genetic similarity between zebrafish and mammals, prolific reproduction and optically transparent embryos, zebrafish is powerful in modeling mammalian cardiac physiology and pathology as well as in large-scale high throughput screening. However, an economical and convenient tool for rapid evaluation of fish cardiac function is still in need. There have been several image analysis methods to assess cardiac functions in zebrafish embryos/larvae, but they are still improvable to reduce manual intervention in the entire process. This work developed a fully automatic method to calculate heart rate, an important parameter to analyze cardiac function, from videos. It contains several filters to identify the heart region, to reduce video noise and to calculate heart rates. The proposed method was evaluated with 32 zebrafish larval cardiac videos that were recording at three-day post-fertilization. The heart rate measured by the proposed method was comparable to that determined by manual counting. The experimental results show that the proposed method does not lose accuracy while largely reducing the labor cost and uncertainty of manual counting. With the proposed method, researchers do not have to manually select a region of interest before analyzing videos. Moreover, filters designed to reduce video noise can alleviate background fluctuations during the video recording stage (e.g. shifting), which makes recorders generate usable videos easily and therefore reduce manual efforts while recording.

Impaired atrioventricular transport in patients with transposition of the great arteries palliated by atrial switch and preserved systolic right ventricular function: A magnetic resonance imaging study.

PubMed

Ladouceur, Magalie; Kachenoura, Nadjia; Soulat, Gilles; Bollache, Emilie; Redheuil, Alban; Azizi, Michel; Delclaux, Christophe; Chatellier, Gilles; Boutouyrie, Pierre; Iserin, Laurence; Bonnet, Damien; Mousseaux, Elie

2017-07-01

We aimed (1) determine if systemic right ventricle filling parameters influence systemic right ventricle stroke volume in adult patients with D-transposition of the great arteries (D-TGA) palliated by atrial switch, using cardiac magnetic resonance imaging and echocardiography, and (2) to study relationship of these diastolic parameters with exercise performance and BNP, in patients with preserved systolic systemic right ventricle function. Single-center, cross-sectional, prospective study. In patients with D-TGA palliated by atrial switch, diastolic dysfunction of the systemic right ventricle may precede systolic dysfunction. Forty-five patients with D-TGA and atrial switch and 45 age and sex-matched healthy subjects underwent cardiac magnetic resonance imaging and echocardiography. Filling flow-rates measured by phase-contrast cardiac magnetic resonance imaging were analyzed using customized software to estimate diastolic parameters and compared with exercise performance. In D-TGA, early filling of systemic right ventricle was impaired with a lower peak filling rate normalized by filling volume (Ef/FV measured by cardiac magnetic resonance imaging) and a higher early filling peak velocity normalized by early peak myocardial velocity (E US /Ea measured by echocardiography) compared with controls (P ≤ .04). Stroke volume of systemic right ventricle showed a direct and significant association with pulmonary venous pathway size (respectively r = 0.50, P < .01). Systemic right atrial area and systemic right ventricle mass/volume index measured by cardiac magnetic resonance imaging, as well as Ef/FV were significantly correlated with exercise performances and BNP (P < .01). All correlations were independent of age, gender, body mass index and blood pressure. Systemic right ventricle pre-load and stroke volume depend mainly on intraatrial pathway function. Moreover, systemic right ventricle remodeling and right atrial dysfunction impair systemic right ventricle filling, leading to BNP increase and exercise limitation. Cardiac magnetic resonance imaging should assess systemic right ventricle filling abnormalities in D-TGA patients. © 2017 Wiley Periodicals, Inc.

Estimation of cardiac left ventricular ejection fraction in transfusional cardiac iron overload by R2* magnetic resonance.

PubMed

Sakuta, Juri; Ito, Yoshikazu; Kimura, Yukihiko; Park, Jinho; Tokuuye, Koichi; Ohyashiki, Kazuma

2010-12-01

Cardiac dysfunction due to transfusional iron overload is one of the most critical complications for patients with transfusion-dependent hematological disorders. Clinical parameters such as total red blood cell (RBC) transfusion units and serum ferritin level are usually considered as indicators for initiation of iron chelation therapy. We used MRI-T2*, MRI-R2* values, and left ventricular ejection fraction in 19 adult patients with blood transfusion-dependent hematological disorders without consecutive oral iron chelation therapy, and propose possible formulae of cardiac function using known parameters, such as total RBC transfusion units and serum ferritin levels. We found a positive correlation in all patients between both R2* values (reciprocal values of T2*) and serum ferritin levels (r = 0.81) and also total RBC transfusion volume (r = 0.90), but not when we analyzed subgroups of patients whose T2* values were over 30 ms (0.52). From the formulae of the R2*, we concluded that approximately 50 Japanese units or 2,900 pmol/L ferritin might be the cutoff value indicating possible future cardiac dysfunction.

Optimization of Electrical Stimulation Parameters for Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

2010-01-01

In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile cardiac tissue constrcuts. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation, to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, and were thus used in tissue engineering studies. Cardiac tissues stimulated at 3V/cm amplitude and 3Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43, and the best developed contractile behavior. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering. PMID:21604379

An exploratory investigation of echocardiographic parameters and the effects of posture on cardiac structure and function in the Livingstone's fruit bat (Pteropus livingstonii).

PubMed

Drane, Aimee L; Shave, Robert; Routh, Andrew; Barbon, Alberto

2018-01-01

There is growing evidence that dilated cardiomyopathy may be a major cause of death in captive Livingstone's fruit bats (Pteropus livingstonii). Therefore, the primary aim of this prospective, exploratory study was to examine whether a systematic cardiac ultrasound protocol is feasible in this critically endangered species and to report basic measures of cardiac structure and function from a cohort of apparently healthy bats. A secondary aim was to test the effect posture (dorsal recumbency vs. roosting) has upon cardiac function in this species. Transthoracic echocardiograms, including 2D, Doppler, and tissue Doppler measures of cardiac structure and function were completed as part of routine health examinations for bats at a single center (n = 19). Bats were then grouped by age and disease status and the mean and range data reported for each group. In healthy adult bats, with the exception of a reduction in heart rate (P ≤ 0.05), right atrial systolic area (P ≤ 0.05), and right ventricular velocity during atrial contraction, there were no significant changes in cardiac structure or function in response to the roosting position. However, in the bats presenting with dilated cardiomyopathy the current data suggest that left ventricular ejection fraction is improved while roosting. Further work is required to confirm our initial findings, generate diagnostic reference intervals, and explore the causes of dilated cardiomyopathy in this species. © 2017 American College of Veterinary Radiology.

Noninvasive pulmonary transit time: A new parameter for general cardiac performance.

PubMed

de Lepper, Anouk G W; Herold, Ingeborg H F; Saporito, Salvatore; Bouwman, R Arthur; Mischi, Massimo; Korsten, Hendrikus H M; Reesink, Koen D; Houthuizen, Patrick

2017-08-01

Pulmonary transit time (PTT) assessed with contrast-enhanced ultrasound (CEUS) is a novel tool to evaluate cardiac function. PTT represents the time for a bolus of contrast to pass from the right to the left ventricle, measured according to the indicator dilution principles using CEUS. We investigated the hypothesis that PTT is a measure of general cardiac performance in patient populations eligible for cardiac resynchronization therapy (CRT). The study population consisted of heart failure patients referred for CRT with NYHA class II-IV, left ventricular ejection fraction (LVEF)≤35% and QRS≥120 ms. CEUS, ECG, and blood were analyzed, and participants completed a quality of life questionnaire at baseline and 3 months after CRT implantation. Normalized PTT (nPTT) was calculated to compensate for the heart rate. Correlations were assessed with Pearson's or Spearman's coefficients and stratified for rhythm and NYHA class. The study population consisted of 94 patients (67 men) with a mean age of 70±8.9 years. (n)PTT was significantly correlated with left ventricular parameters (r s =-.487, P<.001), right ventricular parameters (r=-.282, P=.004), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r s =.475, P<.001), and quality of life (r s =.364, P<.001). Stronger significant correlations were found in patients in sinus rhythm. CEUS-derived PTT and nPTT correlate to a fair degree with measures of systolic and diastolic function, NT-pro-BNP, and quality of life. As CEUS-derived PTT can be obtained easily, noninvasively and at the bedside, it is a promising future measure of general cardiac performance. © 2017, Wiley Periodicals, Inc.

Systolic and diastolic assessment by 3D-ASM segmentation of gated-SPECT Studies: a comparison with MRI

NASA Astrophysics Data System (ADS)

Tobon-Gomez, C.; Bijnens, B. H.; Huguet, M.; Sukno, F.; Moragas, G.; Frangi, A. F.

2009-02-01

Gated single photon emission tomography (gSPECT) is a well-established technique used routinely in clinical practice. It can be employed to evaluate global left ventricular (LV) function of a patient. The purpose of this study is to assess LV systolic and diastolic function from gSPECT datasets in comparison with cardiac magnetic resonance imaging (CMR) measurements. This is achieved by applying our recently implemented 3D active shape model (3D-ASM) segmentation approach for gSPECT studies. This methodology allows for generation of 3D LV meshes for all cardiac phases, providing volume time curves and filling rate curves. Both systolic and diastolic functional parameters can be derived from these curves for an assessment of patient condition even at early stages of LV dysfunction. Agreement of functional parameters, with respect to CMR measurements, were analyzed by means of Bland-Altman plots. The analysis included subjects presenting either LV hypertrophy, dilation or myocardial infarction.

Clinicians' adherence to clinical practice guidelines for cardiac function monitoring during antipsychotic treatment: a retrospective report on 434 patients with severe mental illness.

PubMed

Manchia, Mirko; Firinu, Giorgio; Carpiniello, Bernardo; Pinna, Federica

2017-03-31

Severe mental illness (SMI) has considerable excess morbidity and mortality, a proportion of which is explained by cardiovascular diseases, caused in part by antipsychotic (AP) induced QT-related arrhythmias and sudden death by Torsade de Point (TdP). The implementation of evidence-based recommendations for cardiac function monitoring might reduce the incidence of these AP-related adverse events. To investigate clinicians' adherence to cardiac function monitoring before and after starting AP, we performed a retrospective assessment of 434 AP-treated SMI patients longitudinally followed-up for 5 years at an academic community mental health center. We classified antipsychotics according to their risk of inducing QT-related arrhythmias and TdP (Center for Research on Therapeutics, University of Arizona). We used univariate tests and multinomial or binary logistic regression model for data analysis. Univariate and multinomial regression analysis showed that psychiatrists were more likely to perform pre-treatment electrocardiogram (ECG) and electrolyte testing with AP carrying higher cardiovascular risk, but not on the basis of AP pharmacological class. Univariate and binomial regression analysis showed that cardiac function parameters (ECG and electrolyte balance) were more frequently monitored during treatment with second generation AP than with first generation AP. Our data show the presence of weaknesses in the cardiac function monitoring of AP-treated SMI patients, and might guide future interventions to tackle them.

Cannabinoid receptor 1 inhibition improves cardiac function and remodelling after myocardial infarction and in experimental metabolic syndrome.

PubMed

Slavic, Svetlana; Lauer, Dilyara; Sommerfeld, Manuela; Kemnitz, Ulrich Rudolf; Grzesiak, Aleksandra; Trappiel, Manuela; Thöne-Reineke, Christa; Baulmann, Johannes; Paulis, Ludovit; Kappert, Kai; Kintscher, Ulrich; Unger, Thomas; Kaschina, Elena

2013-07-01

The cannabinoid receptors, CB1 and CB2, are expressed in the heart, but their role under pathological conditions remains controversial. This study examined the effect of CB1 receptor blockade on cardiovascular functions after experimental MI and in experimental metabolic syndrome. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the CB1 receptor antagonist rimonabant (10 mg/kg i.p. daily) started 7 days before or 6 h after MI and continued for 6 weeks. Haemodynamic parameters were measured via echocardiography and intracardiac Samba catheter. CB1 blockade improved systolic and diastolic heart function, decreased cardiac collagen and hydroxyproline content and down-regulated TGF-β1. Additionally, rimonabant decreased arterial stiffness, normalised QRS complex duration and reduced brain natriuretic peptide levels in serum. In primary cardiac fibroblasts, rimonabant decreased MMP-9 activity and TGF-β1 expression. Furthermore, rimonabant improved depressed systolic function of spontaneously hypertensive obese rats and reduced weight gain. Blocking of CB1 receptor with rimonabant improves cardiac functions in the early and late stages after MI, decreases arterial stiffness and reduces cardiac remodelling. Rimonabant also has cardioprotective actions in rats characterised by the metabolic syndrome. Inhibition of proteolysis and TGF-β1 expression and reduced collagen content by rimonabant may attenuate destruction of the extracellular matrix and decrease fibrosis after MI.

Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis

PubMed Central

Susantitaphong, Paweena; Koulouridis, Ioannis; Balk, Ethan M.; Madias, Nicolaos E.; Jaber, Bertrand L.

2012-01-01

Background Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. Study Design Meta-analysis. Setting & Population MEDLINE literature search (inception-April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms “short daily HD”, “daily HD”, “quotidian HD”, “frequent HD”, “intensive HD”, “nocturnal HD”, and “home HD”. Selection Criteria for Studies Single-arm cohort studies (with pre- and post-study evaluations) and randomized controlled trials examining the effect of frequent or extended HD on cardiac morphology and function, and blood pressure parameters. Studies of hemofiltration, hemodiafiltration and peritoneal dialysis were excluded. Intervention Frequent (2–8 hours,> thrice weekly) or extended (>4 hours, thrice weekly) HD as compared with conventional (≤ 4 hours, thrice weekly) HD. Outcomes Absolute changes in cardiac morphology and function, including LV mass index (LVMI) (primary), and blood pressure parameters (secondary). Results We identified 38 single-arm studies, 5 crossover trials and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (−31.2 g/m2, 95% CI, −39.8 to −22.5; P<0.001).The 3 randomized trials found a less pronounced net reduction in LVMI (−7.0 g/m2; 95% CI, −10.2 to −3.7; P<0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6 to 11.9; P=0.01). Other cardiac morphological parameters displayed similar improvements. There were also significant decreases in systolic, diastolic, and mean blood pressure, and mean number of anti-hypertensive medications. Limitations Paucity of randomized controlled trials. Conclusions Conversion from conventional to frequent or extended HD is associated with an improvement in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and in several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed. PMID:22370022

Machine Learning of Human Pluripotent Stem Cell-Derived Engineered Cardiac Tissue Contractility for Automated Drug Classification.

PubMed

Lee, Eugene K; Tran, David D; Keung, Wendy; Chan, Patrick; Wong, Gabriel; Chan, Camie W; Costa, Kevin D; Li, Ronald A; Khine, Michelle

2017-11-14

Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a daunting challenge. Immense research effort has been focused toward creating new screening platforms that utilize human pluripotent stem cell (hPSC)-derived cardiomyocytes and three-dimensional engineered cardiac tissue constructs to better recapitulate human heart function and drug responses. As these new platforms become increasingly sophisticated and high throughput, the drug screens result in larger multidimensional datasets. Improved automated analysis methods must therefore be developed in parallel to fully comprehend the cellular response across a multidimensional parameter space. Here, we describe the use of machine learning to comprehensively analyze 17 functional parameters derived from force readouts of hPSC-derived ventricular cardiac tissue strips (hvCTS) electrically paced at a range of frequencies and exposed to a library of compounds. A generated metric is effective for then determining the cardioactivity of a given drug. Furthermore, we demonstrate a classification model that can automatically predict the mechanistic action of an unknown cardioactive drug. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of Regression Analysis and Transfer Function in Estimating the Parameters of Central Pulse Waves from Brachial Pulse Wave.

PubMed

Chai, Rui; Xu, Li-Sheng; Yao, Yang; Hao, Li-Ling; Qi, Lin

2017-01-01

This study analyzed ascending branch slope (A_slope), dicrotic notch height (Hn), diastolic area (Ad) and systolic area (As) diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), subendocardial viability ratio (SEVR), waveform parameter (k), stroke volume (SV), cardiac output (CO), and peripheral resistance (RS) of central pulse wave invasively and non-invasively measured. Invasively measured parameters were compared with parameters measured from brachial pulse waves by regression model and transfer function model. Accuracy of parameters estimated by regression and transfer function model, was compared too. Findings showed that k value, central pulse wave and brachial pulse wave parameters invasively measured, correlated positively. Regression model parameters including A_slope, DBP, SEVR, and transfer function model parameters had good consistency with parameters invasively measured. They had same effect of consistency. SBP, PP, SV, and CO could be calculated through the regression model, but their accuracies were worse than that of transfer function model.

Estimation of Pulse Transit Time as a Function of Blood Pressure Using a Nonlinear Arterial Tube-Load Model.

PubMed

Gao, Mingwu; Cheng, Hao-Min; Sung, Shih-Hsien; Chen, Chen-Huan; Olivier, Nicholas Bari; Mukkamala, Ramakrishna

2017-07-01

pulse transit time (PTT) varies with blood pressure (BP) throughout the cardiac cycle, yet, because of wave reflection, only one PTT value at the diastolic BP level is conventionally estimated from proximal and distal BP waveforms. The objective was to establish a technique to estimate multiple PTT values at different BP levels in the cardiac cycle. a technique was developed for estimating PTT as a function of BP (to indicate the PTT value for every BP level) from proximal and distal BP waveforms. First, a mathematical transformation from one waveform to the other is defined in terms of the parameters of a nonlinear arterial tube-load model accounting for BP-dependent arterial compliance and wave reflection. Then, the parameters are estimated by optimally fitting the waveforms to each other via the model-based transformation. Finally, PTT as a function of BP is specified by the parameters. The technique was assessed in animals and patients in several ways including the ability of its estimated PTT-BP function to serve as a subject-specific curve for calibrating PTT to BP. the calibration curve derived by the technique during a baseline period yielded bias and precision errors in mean BP of 5.1 ± 0.9 and 6.6 ± 1.0 mmHg, respectively, during hemodynamic interventions that varied mean BP widely. the new technique may permit, for the first time, estimation of PTT values throughout the cardiac cycle from proximal and distal waveforms. the technique could potentially be applied to improve arterial stiffness monitoring and help realize cuff-less BP monitoring.

M-Mode Echocardiographic Changes in Growing Beagles

PubMed Central

Diez-Prieto, Inmaculada; García-Rodríguez, M Belén; Ríos-Granja, M Angeles; Cano-Rábano, María J; Peña-Penabad, Marina; Pérez-García, Carlos C

2010-01-01

Heart growth in 6 female beagle dogs was measured by using M-mode echocardiography at 4, 7, 10, 13, 17, and 21 mo of age. The same 6 dogs were evaluated throughout the study to establish when cardiac development ends in this breed. The following parameters were measured during systole and diastole: left ventricle posterior wall thickness, interventricular septal thickness, left ventricular internal dimension, left atrial dimension during ventricular systole, aortic root dimension at end diastole, E-point to septal separation, left ventricular preejection period, ejection time of the left ventricular outflow, and time between the cessation and onset of the mitral inflow intervals. The percentage of the left ventricle posterior wall thickening, fractional shortening, ejection fraction, left ventricular end systolic and end-diastolic volumes, ratio of the left atrial dimension to aortic root dimension, and the Tei index of myocardial performance were calculated. The heart rate was measured by cardiac auscultation. The influence of ageing on each echocardiographic parameter and relationships with body weight and surface were studied. Results show that cardiac development in female beagles can be considered finished by the age of 1 y, perhaps as soon as 7 mo. The cardiac indexes studied were unaffected by the age and corporal dimensions, confirming the usefulness of these parameters for evaluating cardiac functionality alterations independent of a dog's age and body weight or surface area. PMID:20122313

Convolutional neural network regression for short-axis left ventricle segmentation in cardiac cine MR sequences.

PubMed

Tan, Li Kuo; Liew, Yih Miin; Lim, Einly; McLaughlin, Robert A

2017-07-01

Automated left ventricular (LV) segmentation is crucial for efficient quantification of cardiac function and morphology to aid subsequent management of cardiac pathologies. In this paper, we parameterize the complete (all short axis slices and phases) LV segmentation task in terms of the radial distances between the LV centerpoint and the endo- and epicardial contours in polar space. We then utilize convolutional neural network regression to infer these parameters. Utilizing parameter regression, as opposed to conventional pixel classification, allows the network to inherently reflect domain-specific physical constraints. We have benchmarked our approach primarily against the publicly-available left ventricle segmentation challenge (LVSC) dataset, which consists of 100 training and 100 validation cardiac MRI cases representing a heterogeneous mix of cardiac pathologies and imaging parameters across multiple centers. Our approach attained a .77 Jaccard index, which is the highest published overall result in comparison to other automated algorithms. To test general applicability, we also evaluated against the Kaggle Second Annual Data Science Bowl, where the evaluation metric was the indirect clinical measures of LV volume rather than direct myocardial contours. Our approach attained a Continuous Ranked Probability Score (CRPS) of .0124, which would have ranked tenth in the original challenge. With this we demonstrate the effectiveness of convolutional neural network regression paired with domain-specific features in clinical segmentation. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous cardiac troponin I release in Fabry disease.

PubMed

Feustel, Andreas; Hahn, Andreas; Schneider, Christian; Sieweke, Nicole; Franzen, Wolfgang; Gündüz, Dursun; Rolfs, Arndt; Tanislav, Christian

2014-01-01

Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD. cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females) regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI). Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05-0.71 ng/ml, normal: <0.01). cMRI disclosed late gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3) in cardiomyocytes. Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD.

Limits of clinical tests to screen autonomic function in diabetes type 1.

PubMed

Ducher, M; Bertram, D; Sagnol, I; Cerutti, C; Thivolet, C; Fauvel, J P

2001-11-01

A precocious detection of cardiac autonomic dysfunction is of major clinical interest that could lead to a more intensive supervision of diabetic patients. However, classical clinical exploration of cardiac autonomic function is not easy to undertake in a reproducible way. Thus, respective interests of autonomic nervous parameters provided by both clinical tests and computerized analysis of resting blood pressure were checked in type 1 diabetic patients without orthostatic hypotension and microalbuminuria. Thirteen diabetic subjects matched for age and gender to thirteen healthy subjects volunteered to participate to the study. From clinical tests (standing up, deep breathing, Valsalva maneuver, handgrip test), autonomic function was scored according to Ewing's methodology. Analysis of resting beat to beat blood pressure provided autonomic indices of the cardiac function (spectral analysis or Z analysis). 5 of the 13 diabetic patients exhibited a pathological score (more than one pathological response) suggesting the presence of cardiovascular autonomic dysfunction. The most discriminative test was the deep breathing test. However, spectral indices of BP recordings and baro-reflex sensitivity (BRS) of these 5 subjects were similar to those of healthy subjects and of remaining diabetic subjects. Alteration in Ewing's score given by clinical tests may not reflect an alteration of cardiac autonomic function in asymptomatic type 1 diabetic patients, because spectral indices of sympathetic and parasympathetic (including BRS) function were within normal range. Our results strongly suggest to confront results provided by both methodologies before concluding to an autonomic cardiac impairment in asymptomatic diabetic patients.

Impact of specific training and competition on myocardial structure and function in different age ranges of male handball players.

PubMed

Agrebi, Brahim; Tkatchuk, Vladimir; Hlila, Nawel; Mouelhi, Emna; Belhani, Ali

2015-01-01

Handball activity involves cardiac changes and demands a mixture of both eccentric and concentric remodeling within the heart. This study seeks to explore heart performance and cardiac remodeling likely to define cardiac parameters which influence specific performance in male handball players across different age ranges. Forty three players, with a regular training and competitive background in handball separated into three groups aged on average 11.78 ± 0.41 for youth players aka "schools", "elite juniors" 15.99 ± 0.81 and "elite adults" 24.46 ± 2.63 years, underwent echocardiography and ECG examinations. Incremental ergocycle and specific field (SFT) tests have also been conducted. With age and regular training and competition, myocardial remodeling in different age ranges exhibit significant differences in dilatation's parameters between "schools" and "juniors" players, such as the end-diastolic diameter (LVEDD) and the end-systolic diameter of the left ventricle (LVESD), the root of aorta (Ao) and left atrial (LA), while significant increase is observed between "juniors" and "adults" players in the interventricular septum (IVS), the posterior wall thicknesses (PWT) and LV mass index. ECG changes are also noted but NS differences were observed in studied parameters. For incremental maximal test, players demonstrate a significant increase in duration and total work between "schools" and "juniors" and, in total work only, between "juniors" and "seniors". The SFT shows improvement in performance which ranged between 26.17 ± 1.83 sec to 31.23 ± 2.34 sec respectively from "seniors" to "schools". The cross-sectional approach used to compare groups with prior hypothesis that there would be differences in exercise performance and cardiac parameters depending on duration of prior handball practice, leads to point out the early cardiac remodeling within the heart as adaptive change. Prevalence of cardiac chamber dilation with less hypertrophy remodeling was found from "schools" to "juniors" while a prevalence of cardiac hypertrophy with less pronounced chamber dilation remodeling was noted later.

Calcineurin Regulates Myocardial Function during Acute Endotoxemia

PubMed Central

Joshi, Mandar S.; Julian, Mark W.; Huff, Jennifer E.; Bauer, John A.; Xia, Yong; Crouser, Elliott D.

2006-01-01

Rationale: Cyclosporin A (CsA) is known to preserve cardiac contractile function during endotoxemia, but the mechanism is unclear. Increased nitric oxide (NO) production and altered mitochondrial function are implicated as mechanisms contributing to sepsis-induced cardiac dysfunction, and CsA has the capacity to reduce NO production and inhibit mitochondrial dysfunction relating to the mitochondrial permeability transition (MPT). Objectives: We hypothesized that CsA would protect against endotoxin-mediated cardiac contractile dysfunction by attenuating NO production and preserving mitochondrial function. Methods: Left ventricular function was measured continuously over 4 h in cats assigned as follows: control animals (n = 7); LPS alone (3 mg/kg, n = 8); and CsA (6 mg/kg, n = 7), a calcineurin inhibitor that blocks the MPT, or tacrolimus (FK506, 0.1 mg/kg, n = 7), a calcineurin inhibitor lacking MPT activity, followed in 30 min by LPS. Myocardial tissue was then analyzed for NO synthase-2 expression, tissue nitration, protein carbonylation, and mitochondrial morphology and function. Measurements and Main Results: LPS treatment resulted in impaired left ventricular contractility, altered mitochondrial morphology and function, and increased protein nitration. As hypothesized, CsA pretreatment normalized cardiac performance and mitochondrial respiration and reduced myocardial protein nitration. Unexpectedly, FK506 pretreatment had similar effects, normalizing both cardiac and mitochondrial parameters. However, CsA and FK506 pretreatments markedly increased protein carbonylation in the myocardium despite elevated manganese superoxide dismutase activity during endotoxemia. Conclusions: Our data indicate that calcineurin is a critical regulator of mitochondrial respiration, tissue nitration, protein carbonylation, and contractile function in the heart during acute endotoxemia. PMID:16424445

[Individual typological peculiarities of system blood flow, physical capacity for work and cardiac activity regulation in patients with different resistance to periodontal diseases].

PubMed

Bragin, A V

2008-01-01

From position of typological variability of physiological individuality concept-functional constitution types - the principle of organism integrity was substantiated for stomatological pathology. There were isolated typical and specific reactions of cardiac-vessel system in patients with different resistance to periodontal diseases. Each functional type - patients with different levels of usual motion activity - had their own physiological peculiarities of parameters of system blood flow, physical capacity for work and cardiac activity regulation, that determined individual typological organism reaction in cases of maxillo-facial system pathology. The received data gives the objective base for physiological approach to single out the extreme variants of norm for forming risk contingent and groups of resistant people to periodontal diseases.

Respiratory motion compensated overlay of surface models from cardiac MR on interventional x-ray fluoroscopy for guidance of cardiac resynchronization therapy procedures

NASA Astrophysics Data System (ADS)

Manzke, R.; Bornstedt, A.; Lutz, A.; Schenderlein, M.; Hombach, V.; Binner, L.; Rasche, V.

2010-02-01

Various multi-center trials have shown that cardiac resynchronization therapy (CRT) is an effective procedure for patients with end-stage drug invariable heart failure (HF). Despite the encouraging results of CRT, at least 30% of patients do not respond to the treatment. Detailed knowledge of the cardiac anatomy (coronary venous tree, left ventricle), functional parameters (i.e. ventricular synchronicity) is supposed to improve CRT patient selection and interventional lead placement for reduction of the number of non-responders. As a pre-interventional imaging modality, cardiac magnetic resonance (CMR) imaging has the potential to provide all relevant information. With functional information from CMR optimal implantation target sites may be better identified. Pre-operative CMR could also help to determine whether useful vein target segments are available for lead placement. Fused with X-ray, the mainstay interventional modality, improved interventional guidance for lead-placement could further help to increase procedure outcome. In this contribution, we present novel and practicable methods for a) pre-operative functional and anatomical imaging of relevant cardiac structures to CRT using CMR, b) 2D-3D registration of CMR anatomy and functional meshes with X-ray vein angiograms and c) real-time capable breathing motion compensation for improved fluoroscopy mesh overlay during the intervention based on right ventricular pacer lead tracking. With these methods, enhanced interventional guidance for left ventricular lead placement is provided.

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using "Braslet-M" Occlusion Cuffs

NASA Technical Reports Server (NTRS)

Hamilton, D. R.; Sargsyan, A. E.; Garcia, K. M.; Ebert, D.; Feiveson, A. H.; Alferova, I. V.; Dulchavsky, S. A.; Matveev, V. P.; Bogomolov, V. V.; Duncan, J. M.

2011-01-01

BACKGROUND: The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, nasal congestion, and headache. This experiment examined the responses to modified Valsalva and Mueller maneuvers as measured by cardiac and vascular ultrasound in a baseline microgravity steady state, and under the influence of thigh occlusion cuffs (Braslet cuffs). METHODS: Nine International Space Station crewmember subjects (Expeditions 16 - 20) were examined in 15 experiment sessions 101 46 days after launch (mean SD; 33 - 185). 27 cardiac and vascular parameters were obtained under three respiratory conditions (baseline, Valsalva, and Mueller) before and after tightening of the Braslet cuffs for a total of 162 data points per session. The quality of cardiac and vascular ultrasound examinations was assured through remote monitoring and guidance by Investigators from the NASA Telescience Center in Houston, TX, USA. RESULTS: Fourteen of the 81 measured conditions were significantly different with Braslet application and were apparently related to cardiac preload reduction or increase in the venous volume sequestered in the lower extremity. These changes represented 10 of the 27 parameters measured. In secondary analysis, 7 of the 27 parameters were found to respond differently to respiratory maneuvers depending on the presence or absence of thigh compression, with a total of 11 differences. CONCLUSIONS: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts proportionate measurable effects on cardiac performance in microgravity. Ultrasound techniques measuring the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an effective tool in determining the volume status of a cardiac or hemodynamically compromised patient in microgravity.

The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors.

PubMed

Arioglu, E; Guner, S; Ozakca, I; Altan, V M; Ozcelikay, A T

2010-02-01

Thyroid hormone deficiency has been reported to decrease expression and function of both beta(1)- and beta(2)-adrenoceptor in different tissues including heart. The purpose of this study was to examine the possible contribution of beta(3)-adrenoceptors to cardiac dysfunction in hypothyroidism. In addition, effect of this pathology on beta(1)- and beta(2)-adrenoceptor was investigated. Hypothyroidism was induced by adding methimazole (300 mg/l) to drinking water of rats for 8 weeks. Cardiac hemodynamic parameters were measured in anesthetised rats in vivo. Responses to beta-adrenoceptor agonists were examined in rat papillary muscle in vitro. We also studied the effect of hypotyroidism on mRNA expression of beta-adrenoceptors, Gialpha, GRK, and eNOS in rat heart. All of the hemodynamic parameters (systolic, diastolic and mean arterial pressure, left ventricular pressure, heart rate, +dp/dt, and -dp/dt) were significantly reduced by the methimazole treatment. The negative inotropic effect elicited by BRL 37344 (a beta(3)-adrenoceptor preferential agonist) and positive inotropic effects produced by isoprenaline and noradrenaline, respectively, were significantly decreased in papillary muscle of hypothyroid rats as compared to those of controls. On the other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions. However, beta(1)-adrenoceptor and GRK2 mRNA expressions were not changed significantly in this pathology. These results show that mRNA expression of beta(3)-adrenoceptors as well as the signalling pathway components mediated through beta(3)-adrenoceptors are significantly increased in hypothyroid rat heart. Since we could not correlate these alternates with the decreased negative inotropic response mediated by this receptor subtype, it is not clear whether these changes are important for hypothyroid induced reduction in cardiac function.

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress.

PubMed

Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2016-01-01

The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=-0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=-0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=-0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction, inflammation, and oxidative stress.

The Toxicity of Inhaled Sulphur Mustard

DTIC Science & Technology

2012-03-01

Pulse oximetry Mean arterial pressure Central venous pressure Blood Chemistry (arterial and venous ) pH pO2 pCO2 Sodium Potassium Calcium...Cardiovascular Parameters − CFI – Cardiac Function Index − CO – Cardiac Output − CvO2 – Mixed Venous Oxygenation − CVP – Central Venous Pressure...Data are expressed as mean ± SEM. Changes in central venous pressure following exposure to HD: HD controls () and HD + NAC (). Data are

Assessing the effect of preoperative levosimendan on renal function in patients with right ventricular dysfunction.

PubMed

Guerrero Orriach, Jose L; Galán Ortega, M; Ramírez Fernandez, A; Ariza Villanueva, D; Florez Vela, A; Moreno Cortés, I; Rubio Navarro, M; Cruz Mañas, J

2017-02-01

The Acute Kidney Injury Network (AKIN) classification considers SCr values, urea and urine output in order to improve timely diagnose ARF and improve patient prognosis by early treatment. Preoperative levosimendan is a new way for cardiac and kidney protection, we try to evaluate this drug in fifteen patients comparing values of AKIN scale parameters pre and post cardiac surgery in patients with right ventricle dysfunction.

Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction.

PubMed

Xiong, Liang; Liu, Yu; Zhou, Mingmin; Wang, Guangji; Quan, Dajun; Shen, Caijie; Shuai, Wei; Kong, Bin; Huang, Congxin; Huang, He

2018-05-31

The purpose of this study was to evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI). Thirty-eight anaesthetized dogs were randomly assigned into the sham-operated, MI, and MI-TACSN groups, respectively. Myocardial infarction-targeted ablation of cardiac sympathetic neuron was induced by injecting cholera toxin B subunit-saporin compound in the left stellate ganglion (LSG). Five weeks after surgery, the cardiac function, heart rate variability (HRV), ventricular electrophysiological parameters, LSG function and neural activity, serum norepinephrine (NE), nerve growth factor (NGF), and brain natriuretic peptide (BNP) levels were measured. Cardiac sympathetic innervation was determined with immunofluorescence staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Compared with MI group, TACSN significantly improved HRV, attenuated LSG function and activity, prolonged corrected QT interval, decreased Tpeak-Tend interval, prolonged ventricular effective refractory period (ERP), and action potential duration (APD), decreased the slopes of APD restitution curves, suppressed the APD alternans, increased ventricular fibrillation threshold, and reduced serum NE, NGF, and BNP levels. Moreover, the densities of GAP43 and TH-positive nerve fibres in the infarcted border zone in the MI-TACSN group were lower than those in the MI group. Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats.

PubMed

Luck, Christian; DeMarco, Vincent G; Mahmood, Abuzar; Gavini, Madhavi P; Pulakat, Lakshmi

2017-01-01

Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750  μ g/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters ( E / E ', E '/ A ', E / Vp ) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFN γ , and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.

Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

PubMed Central

Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

2017-01-01

Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes. PMID:28408970

USPIO-enhanced 3D-cine self-gated cardiac MRI based on a stack-of-stars golden angle short echo time sequence: Application on mice with acute myocardial infarction.

PubMed

Trotier, Aurélien J; Castets, Charles R; Lefrançois, William; Ribot, Emeline J; Franconi, Jean-Michel; Thiaudière, Eric; Miraux, Sylvain

2016-08-01

To develop and assess a 3D-cine self-gated method for cardiac imaging of murine models. A 3D stack-of-stars (SOS) short echo time (STE) sequence with a navigator echo was performed at 7T on healthy mice (n = 4) and mice with acute myocardial infarction (MI) (n = 4) injected with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. In all, 402 spokes were acquired per stack with the incremental or the golden angle method using an angle increment of (360/402)° or 222.48°, respectively. A cylindrical k-space was filled and repeated with a maximum number of repetitions (NR) of 10. 3D cine cardiac images at 156 μm resolution were reconstructed retrospectively and compared for the two methods in terms of contrast-to-noise ratio (CNR). The golden angle images were also reconstructed with NR = 10, 6, and 3, to assess cardiac functional parameters (ejection fraction, EF) on both animal models. The combination of 3D SOS-STE and USPIO injection allowed us to optimize the identification of cardiac peaks on navigator signal and generate high CNR between blood and myocardium (15.3 ± 1.0). The golden angle method resulted in a more homogeneous distribution of the spokes inside a stack (P < 0.05), enabling reducing the acquisition time to 15 minutes. EF was significantly different between healthy and MI mice (P < 0.05). The method proposed here showed that 3D-cine images could be obtained without electrocardiogram or respiratory gating in mice. It allows precise measurement of cardiac functional parameters even on MI mice. J. Magn. Reson. Imaging 2016;44:355-365. © 2016 Wiley Periodicals, Inc.

Dragon Boat training exerts a positive effect on myocardial function in breast cancer survivors.

PubMed

Stefani, Laura; Galanti, Giorgio; Di Tante, Valentina; Klika, Riggs J; Maffulli, Nicola

2015-07-01

Dragon Boat training is often suggested to control upper limb edema in breast cancer (BC) survivors, but little information is available regarding the cardiac impact of such activity. The present study evaluates this aspect during a 4-year follow-up of BC survivors. From 2006 to 2010, 55 women diagnosed with BC in 2005, treated with adjuvant therapy without evidence of metastases, were enrolled for competitive Dragon Boat training. They underwent ergometric tests yearly, and 2D echocardiography to evaluate hemodynamic, morphological and functional cardiac parameters. The data were compared with those from a group of 36 healthy women (HW). Both groups maintained normal systolic function throughout the period, with Cardiac Mass index, Body Mass Index and Ejection Fraction values being higher in HW. At the onset of the study, the diastolic function of BC survivors was normal though compatible with initial diastolic dysfunction when compared to the diastolic function of HW. After 4 years of competitive activity, the diastolic parameters improved in both groups and particularly in BC survivors (A peak: from 68.5 ± 15.1 cm/s to 50 ± 14.1 cm/s, p < 0.05; Ea: from 9.3 ± 2 cm/s to 11.89 ± 1.7 cm/s, p < 0.001). BC survivors experienced a significant improvement in diastolic function after 4 years of Dragon Boat training. Dragon Boat training impacts favorably on the myocardial performance in patients previously treated with chemotherapy. These results support the positive role of sport activity in myocardial function of BC survivors.

Assessment of cardiac autonomic functions by heart rate recovery, heart rate variability and QT dynamicity parameters in patients with acromegaly.

PubMed

Dural, Muhammet; Kabakcı, Giray; Cınar, Neşe; Erbaş, Tomris; Canpolat, Uğur; Gürses, Kadri Murat; Tokgözoğlu, Lale; Oto, Ali; Kaya, Ergün Barış; Yorgun, Hikmet; Sahiner, Levent; Dağdelen, Selçuk; Aytemir, Kudret

2014-04-01

Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with acromegaly.

Estimation of cardiac conductivities in ventricular tissue by a variational approach

NASA Astrophysics Data System (ADS)

Yang, Huanhuan; Veneziani, Alessandro

2015-11-01

The bidomain model is the current standard model to simulate cardiac potential propagation. The numerical solution of this system of partial differential equations strongly depends on the model parameters and in particular on the cardiac conductivities. Unfortunately, it is quite problematic to measure these parameters in vivo and even more so in clinical practice, resulting in no common agreement in the literature. In this paper we consider a variational data assimilation approach to estimating those parameters. We consider the parameters as control variables to minimize the mismatch between the computed and the measured potentials under the constraint of the bidomain system. The existence of a minimizer of the misfit function is proved with the phenomenological Rogers-McCulloch ionic model, that completes the bidomain system. We significantly improve the numerical approaches in the literature by resorting to a derivative-based optimization method with settlement of some challenges due to discontinuity. The improvement in computational efficiency is confirmed by a 2D test as a direct comparison with approaches in the literature. The core of our numerical results is in 3D, on both idealized and real geometries, with the minimal ionic model. We demonstrate the reliability and the stability of the conductivity estimation approach in the presence of noise and with an imperfect knowledge of other model parameters.

Nandrolone and resistance training induce heart remodeling: role of fetal genes and implications for cardiac pathophysiology.

PubMed

Tanno, Ana Paula; das Neves, Vander José; Rosa, Kaleizu Teodoro; Cunha, Tatiana Sousa; Giordano, Fernanda Cristina Linarello; Calil, Caroline Morini; Guzzoni, Vinicius; Fernandes, Tiago; de Oliveira, Edilamar Menezes; Novaes, Pedro Duarte; Irigoyen, Maria Cláudia; Moura, Maria José Costa Sampaio; Marcondes, Fernanda Klein

2011-10-24

This study was conducted to assess the isolated and combined effects of nandrolone and resistance training on cardiac morphology, function, and mRNA expression of pathological cardiac hypertrophy markers. Wistar rats were randomly divided into four groups and submitted to 6 weeks of treatment with nandrolone and/or resistance training. Cardiac parameters were determined by echocardiography. Heart was analyzed for collagen infiltration. Real-time RT-PCR was used to assess the pathological cardiac hypertrophy markers. Both resistance training and nandrolone induced cardiac hypertrophy. Nandrolone increased the cardiac collagen content, and reduced the cardiac index in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the ratio of maximum early to late transmitral flow velocity in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the alpha-myosin heavy chain gene expression in both non-trained and trained groups, when compared with the respective vehicle-treated groups. Training reduced the beta-myosin heavy chain gene expression in the groups treated with vehicle and nandrolone. Only the association between training and nandrolone increased the expression of the skeletal alpha-actin gene and atrial natriuretic peptide in the left ventricle. This study indicated that nandrolone, whether associated with resistance training or not, induces cardiac hypertrophy, which is associated with enhanced collagen content, re-expression of fetal genes the in left ventricle, and impaired diastolic and systolic function. Copyright © 2011 Elsevier Inc. All rights reserved.

Characterization of a Cardiorenal-like Syndrome in Aged Chimpanzees (Pan troglodytes).

PubMed

Chilton, J; Wilcox, A; Lammey, M; Meyer, D

2016-03-01

Cardiorenal syndrome involves disease and dysfunction of the heart that leads to progressive renal dysfunction. This study investigated the relationship between cardiac and renal disease in 91 aged chimpanzees at the Alamogordo Primate Facility by evaluation of the medical histories, metabolic parameters, functional measurements of the cardiovascular system, clinical pathology, and histopathology focused on the heart and kidney. Cardiac fibrosis was the most frequent microscopic finding in 82 of 91 animals (90%), followed by glomerulosclerosis with tubulointerstitial fibrosis in 63 of 91 (69%). Cardiac fibrosis with attendant glomerulosclerosis and tubulointerstitial fibrosis was observed in 58 of 91 animals (63%); there was a statistically significant association between the 2 conditions. As the severity of cardiac fibrosis increased, there was corresponding increase in severity of glomerulosclerosis with tubulointerstitial fibrosis. Altered metabolic, cardiovascular, and clinical pathology parameters indicative of heart and kidney failure were commonly associated with the moderate to severe microscopic changes, and concurrent heart and kidney failure were considered the cause of death. The constellation of findings in the chimpanzees were similar to cardiorenal syndrome in humans. © The Author(s) 2016.

The challenge of cardiac modeling--interaction and integration.

PubMed

Sideman, Samuel

2006-10-01

The goal of clinical cardiology is to obtain an integrated picture of the interacting parameters of muscle and vessel mechanics, blood circulation and myocardial perfusion, oxygen consumption and energy metabolism, and electrical activation and heart rate, thus relating to the true physiological and pathophysiological characteristics of the heart. Scientific insight into the cardiac physiology and performance is achieved by utilizing life sciences, for example, molecular biology, genetics and related intra- and intercellular phenomena, as well as the exact sciences, for example, mathematics, computer science, and related imaging and visualization techniques. The tools to achieve these goals are based on the intimate interactions between engineering science and medicine and the developments of modern, medically oriented technology. Most significant is the beneficiary effect of the globalization of science, the Internet, and the unprecedented international interaction and scientific cooperation in facing difficult multidisciplined challenges. This meeting aims to explore some important interactions in the cardiac system and relate to the integration of spatial and temporal interacting system parameters, so as to gain better insight into the structure and function of the cardiac system, thus leading to better therapeutic modalities.

Moderate intensity exercise prevents diabetic cardiomyopathy associated contractile dysfunction through restoration of mitochondrial function and connexin 43 levels in db/db mice.

PubMed

Veeranki, Sudhakar; Givvimani, Srikanth; Kundu, Sourav; Metreveli, Naira; Pushpakumar, Sathnur; Tyagi, Suresh C

2016-03-01

Although the cardiovascular benefits of exercise are well known, exercise induced effects and mechanisms in prevention of cardiomyopathy are less clear during obesity associated type-2 diabetes. The current study assessed the impact of moderate intensity exercise on diabetic cardiomyopathy by examining cardiac function and structure and mitochondrial function. Obese-diabetic (db/db), and lean control (db/+) mice, were subjected to a 5 week, 300 m run on a tread-mill for 5 days/week at the speeds of 10-11 m/min. Various physiological parameters were recorded and the heart function was evaluated with M-mode echocardiography. Contraction parameters and calcium transits were examined on isolated cardiomyocytes. At the molecular level: connexin 43 and 37 (Cx43 and 37) levels, mitochondrial biogenesis regulators: Mfn2 and Drp-1 levels, mitochondrial trans-membrane potential and cytochrome c leakage were assessed through western blotting immunohistochemistry and flow cytometry. Ability of exercise to reverse oxygen consumption rate (OCR), tissue ATP levels, and cardiac fibrosis were also determined. The exercise regimen was able to prevent diabetic cardiac functional deficiencies: ejection fraction (EF) and fractional shortening (FS). Improvements in contraction velocity and contraction maximum were noted with the isolated cardiomyocytes. Restoration of interstitial and micro-vessels associated Cx43 levels and improved gap junction intercellular communication (GJIC) were observed. The decline in the Mfn2/Drp-1 ratio in the db/db mice hearts was prevented after exercise. The exercise regimen further attenuated transmembrane potential decline and cytochrome c leakage. These corrections further led to improvements in OCR and tissue ATP levels and reduction in cardiac fibrosis. Moderate intensity exercise produced significant cardiovascular benefits by improving mitochondrial function through restoration of Cx43 networks and mitochondrial trans-membrane potential and prevention of excessive mitochondrial fission. Copyright © 2016 Elsevier Ltd. All rights reserved.

Continuous Cardiac Troponin I Release in Fabry Disease

PubMed Central

Schneider, Christian; Sieweke, Nicole; Franzen, Wolfgang; Gündüz, Dursun; Rolfs, Arndt

2014-01-01

Background Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD. Methods cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females) regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI). Results Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05–0.71 ng/ml, normal: <0.01). cMRI disclosed late gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3) in cardiomyocytes. Conclusion Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD. PMID:24626231

A Tocotrienol-Enriched Formulation Protects against Radiation-Induced Changes in Cardiac Mitochondria without Modifying Late Cardiac Function or Structure

PubMed Central

Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K.; Moros, Eduardo G.; Melnyk, Stepan B.; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

2015-01-01

Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling. PMID:25710576

A tocotrienol-enriched formulation protects against radiation-induced changes in cardiac mitochondria without modifying late cardiac function or structure.

PubMed

Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K; Moros, Eduardo G; Melnyk, Stepan B; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

2015-03-01

Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling.

Acute effect of Vagus nerve stimulation parameters on cardiac chronotropic, inotropic, and dromotropic responses

NASA Astrophysics Data System (ADS)

Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

2017-11-01

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression, and is considered as a potential therapy for other pathologies, including Heart Failure (HF) or inflammatory diseases. In the case of HF, several experimental studies on animals have shown an improvement in the cardiac function and a reverse remodeling of the cardiac cavity when VNS is applied. However, recent clinical trials have not been able to reproduce the same response in humans. One of the hypothesis to explain this lack of response is related to the way in which stimulation parameters are defined. The combined effect of VNS parameters is still poorly-known, especially in the case of VNS synchronously delivered with cardiac activity. In this paper, we propose a methodology to analyze the acute cardiovascular effects of VNS parameters individually, as well as their interactive effects. A Latin hypercube sampling method was applied to design a uniform experimental plan. Data gathered from this experimental plan was used to produce a Gaussian process regression (GPR) model in order to estimate unobserved VNS sequences. Finally, a Morris screening sensitivity analysis method was applied to each obtained GPR model. Results highlight dominant effects of pulse current, pulse width and number of pulses over frequency and delay and, more importantly, the degree of interactions between these parameters on the most important acute cardiovascular responses. In particular, high interacting effects between current and pulse width were found. Similar sensitivity profiles were observed for chronotropic, dromotropic and inotropic effects. These findings are of primary importance for the future development of closed-loop, personalized neuromodulator technologies.

Improved Estimation of Cardiac Function Parameters Using a Combination of Independent Automated Segmentation Results in Cardiovascular Magnetic Resonance Imaging.

PubMed

Lebenberg, Jessica; Lalande, Alain; Clarysse, Patrick; Buvat, Irene; Casta, Christopher; Cochet, Alexandre; Constantinidès, Constantin; Cousty, Jean; de Cesare, Alain; Jehan-Besson, Stephanie; Lefort, Muriel; Najman, Laurent; Roullot, Elodie; Sarry, Laurent; Tilmant, Christophe; Frouin, Frederique; Garreau, Mireille

2015-01-01

This work aimed at combining different segmentation approaches to produce a robust and accurate segmentation result. Three to five segmentation results of the left ventricle were combined using the STAPLE algorithm and the reliability of the resulting segmentation was evaluated in comparison with the result of each individual segmentation method. This comparison was performed using a supervised approach based on a reference method. Then, we used an unsupervised statistical evaluation, the extended Regression Without Truth (eRWT) that ranks different methods according to their accuracy in estimating a specific biomarker in a population. The segmentation accuracy was evaluated by estimating six cardiac function parameters resulting from the left ventricle contour delineation using a public cardiac cine MRI database. Eight different segmentation methods, including three expert delineations and five automated methods, were considered, and sixteen combinations of the automated methods using STAPLE were investigated. The supervised and unsupervised evaluations demonstrated that in most cases, STAPLE results provided better estimates than individual automated segmentation methods. Overall, combining different automated segmentation methods improved the reliability of the segmentation result compared to that obtained using an individual method and could achieve the accuracy of an expert.

Improved Estimation of Cardiac Function Parameters Using a Combination of Independent Automated Segmentation Results in Cardiovascular Magnetic Resonance Imaging

PubMed Central

Lebenberg, Jessica; Lalande, Alain; Clarysse, Patrick; Buvat, Irene; Casta, Christopher; Cochet, Alexandre; Constantinidès, Constantin; Cousty, Jean; de Cesare, Alain; Jehan-Besson, Stephanie; Lefort, Muriel; Najman, Laurent; Roullot, Elodie; Sarry, Laurent; Tilmant, Christophe

2015-01-01

This work aimed at combining different segmentation approaches to produce a robust and accurate segmentation result. Three to five segmentation results of the left ventricle were combined using the STAPLE algorithm and the reliability of the resulting segmentation was evaluated in comparison with the result of each individual segmentation method. This comparison was performed using a supervised approach based on a reference method. Then, we used an unsupervised statistical evaluation, the extended Regression Without Truth (eRWT) that ranks different methods according to their accuracy in estimating a specific biomarker in a population. The segmentation accuracy was evaluated by estimating six cardiac function parameters resulting from the left ventricle contour delineation using a public cardiac cine MRI database. Eight different segmentation methods, including three expert delineations and five automated methods, were considered, and sixteen combinations of the automated methods using STAPLE were investigated. The supervised and unsupervised evaluations demonstrated that in most cases, STAPLE results provided better estimates than individual automated segmentation methods. Overall, combining different automated segmentation methods improved the reliability of the segmentation result compared to that obtained using an individual method and could achieve the accuracy of an expert. PMID:26287691

Assessment of the Cardiac Autonomic Nervous System in Mercury-Exposed Individuals via Post-Exercise Heart Rate Recovery.

PubMed

Yilmaz, Omer Hinc; Karakulak, Ugur Nadir; Tutkun, Engin; Bal, Ceylan; Gunduzoz, Meside; Ercan Onay, Emine; Ayturk, Mehmet; Tek Ozturk, Mujgan; Alaguney, Mehmet Erdem

The aim of this study was to assess exercise heart rate recovery (HRR) indices in mercury-exposed individuals when evaluating their cardiac autonomic function. Twenty-eight mercury-exposed individuals and 28 healthy controls were enrolled. All the subjects underwent exercise testing and transthoracic echocardiography. The HRR indices were calculated by subtracting the first- (HRR1), second- (HRR2) and third-minute (HRR3) heart rates from the maximal heart rate. The two groups were evaluated in terms of exercise test parameters, especially HRR, and a correlation analysis was performed between blood, 24-hour urine and hair mercury levels and the test parameters. The mercury-exposed and control groups were similar in age (37.2 ± 6.6 vs. 36.9 ± 9.0 years), had an identical gender distribution (16 females and 12 males) and similar left ventricular ejection fractions (65.5 ± 3.1 vs. 65.4 ± 3.1%). The mean HRR1 [25.6 ± 6.5 vs. 30.3 ± 8.2 beats per min (bpm); p = 0.009], HRR2 (43.5 ± 5.3 vs. 47.8 ± 5.5 bpm; p = 0.010) and HRR3 (56.8 ± 5.1 vs. 59.4 ± 6.3 bpm; p = 0.016) values were significantly lower in the mercury-exposed group than in the healthy controls. However, there were no significant correlations between blood, urine and hair mercury levels and exercise test parameters. Mercury-exposed individuals had lower HRR indices than normal subjects. In these individuals, mercury exposure measurements did not show correlations with the exercise test parameters, but age did show a negative correlation with these parameters. Therefore, cardiac autonomic functions might be involved in cases of mercury exposure. © 2016 S. Karger AG, Basel.

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Inverse computation for cardiac sources using single current dipole and current multipole models

NASA Astrophysics Data System (ADS)

Wang, Qian; Ma, Ping; Lu, Hong; Tang, Xue-Zheng; Hua, Ning; Tang, Fa-Kuan

2009-12-01

Two cardiac functional models are constructed in this paper. One is a single current model and the other is a current multipole model. Parameters denoting the properties of these two models are calculated by a least-square fit to the measurements using a simulated annealing algorithm. The measured signals are detected at 36 observation nodes by a superconducting quantum interference device (SQUID). By studying the trends of position, orientation and magnitude of the single current dipole model and the current multipole model in the QRS complex during one time span and comparing the reconstructed magnetocardiography (MCG) of these two cardiac models, we find that the current multipole model is a more appropriate model to represent cardiac electrophysiological activity.

Integration of multiple cell-matrix interactions into alginate scaffolds for promoting cardiac tissue regeneration.

PubMed

Sapir, Yulia; Kryukov, Olga; Cohen, Smadar

2011-03-01

Cardiac tissue engineering aims to repair damaged myocardial tissues by applying heart patches created in vitro. Herein, we explored the possible role of a combination of two matrix-attached peptides, the adhesion peptide G(4)RGDY and heparin-binding peptide G(4)SPPRRARVTY (HBP) in cardiac tissue regeneration. Neonatal rat cardiac cells were seeded into unmodified, single peptide or double peptide-attached alginate scaffolds, all having the same physical features of porosity, hydrogel forming and matrix stiffness. The cardiac tissue developed in the HBP/RGD-attached scaffolds revealed the best features of a functional muscle tissue, as judged by all studied parameters, i.e., immunostaining of cardiac cell markers, histology, western blot of protein expressions and metabolic activity. By day 7, well-developed myocardial fibers were observed in these cell constructs. At 14 days the HBP/RGD-attached constructs presented an isotropic myofiber arrangement, while no such arrangement was seen in the other constructs. The expression levels of α-actinin, N-cadherin and Connexin-43, showing preservation and an increase in Connexin-43 expression (Cx-43) with time, further supported the formation a contractile muscle tissue in the HBP/RGD-attached scaffolds. Collectively, the attachment of combinatorial peptides representing different signaling in ECM-cell interactions proved to play a key role, contributing to the formation of a functional cardiac muscle tissue, in vitro. Copyright © 2010 Elsevier Ltd. All rights reserved.

Pyridostigmine ameliorates cardiac remodeling induced by myocardial infarction via inhibition of the transforming growth factor-β1/TGF-β1-activated kinase pathway.

PubMed

Lu, Yi; Liu, Jin-Jun; Bi, Xue-Yuan; Yu, Xiao-Jiang; Kong, Shan-Shan; Qin, Fang-Fang; Zhou, Jun; Zang, Wei-Jin

2014-05-01

Autonomic imbalance characterized by sympathetic predominance coinciding with diminished vagal activity is an independent risk factor in cardiovascular diseases. Several studies show that vagus nerve stimulation exerted beneficial effects on cardiac function and survival. In this study, we investigated the vagomimetic effect of pyridostigmine on left ventricular (LV) remodeling in rats after myocardial infarction. After myocardial infarction, surviving rats were treated with or without pyridostigmine (31 mg·kg⁻¹·d⁻¹) for 2 weeks, and hemodynamic parameters were measured. LV tissue was used to assess infarct size and interstitial fibrosis by Masson's trichrome and 0.1% picrosirius red staining. Protein expression of heart tissues was used to assess the efficacy of the treatment. Pyridostigmine markedly reduced myocardial infarct size and improved cardiac diastolic function. These improvements were accompanied with a significant decrease in matrix metalloproteinase-2 expression and collagen deposition. Additionally, pyridostigmine inhibited both transforming growth factor-β1 (TGF-β1) and TGF-β1-activated kinase expression in hearts postmyocardial infarction. Thus, pyridostigmine reduces collagen deposition, attenuates cardiac fibrosis, and improves LV diastolic function after myocardial infarction via TGF-β1/TGF-β1-activated kinase pathway inhibition.

Necessity of angiotensin-converting enzyme-related gene for cardiac functions and longevity of Drosophila melanogaster assessed by optical coherence tomography

NASA Astrophysics Data System (ADS)

Liao, Fang-Tsu; Chang, Cheng-Yi; Su, Ming-Tsan; Kuo, Wen-Chuan

2014-01-01

Prior studies have established the necessity of an angiotensin-converting enzyme-related (ACER) gene for heart morphogenesis of Drosophila. Nevertheless, the physiology of ACER has yet to be comprehensively understood. Herein, we employed RNA interference to down-regulate the expression of ACER in Drosophila's heart and swept source optical coherence tomography to assess whether ACER is required for cardiac functions in living adult flies. Several contractile parameters of Drosophila heart, including the heart rate (HR), end-diastolic diameter (EDD), end-systolic diameter (ESD), percent fractional shortening (%FS), and stress-induced cardiac performance, are shown, which are age dependent. These age-dependent cardiac functions declined significantly when ACER was down-regulated. Moreover, the lifespans of ACER knock-down flies were significantly shorter than those of wild-type control flies. Thus, we posit that ACER, the Drosophila ortholog of mammalian angiotensin-converting enzyme 2 (ACE2), is essential for both heart physiology and longevity of animals. Since mammalian ACE2 controls many cardiovascular physiological features and is implicated in cardiomyopathies, our findings that ACER plays conserved roles in genetically tractable animals will pave the way for uncovering the genetic pathway that controls the renin-angiotensin system.

Computational Quantification of the Cardiac Energy Consumption during Intra-Aortic Balloon Pumping Using a Cardiac Electromechanics Model

PubMed Central

Lim, Ki Moo; Lee, Jeong Sang; Gyeong, Min-Soo; Choi, Jae-Sung; Choi, Seong Wook

2013-01-01

To quantify the reduction in workload during intra-aortic balloon pump (IABP) therapy, indirect parameters are used, such as the mean arterial pressure during diastole, product of heart rate and peak systolic pressure, and pressure-volume area. Therefore, we investigated the cardiac energy consumption during IABP therapy using a cardiac electromechanics model. We incorporated an IABP function into a previously developed electromechanical model of the ventricle with a lumped model of the circulatory system and investigated the cardiac energy consumption at different IABP inflation volumes. When the IABP was used at inflation level 5, the cardiac output and stroke volume increased 11%, the ejection fraction increased 21%, the stroke work decreased 1%, the mean arterial pressure increased 10%, and the ATP consumption decreased 12%. These results show that although the ATP consumption is decreased significantly, stroke work is decreased only slightly, which indicates that the IABP helps the failed ventricle to pump blood efficiently. PMID:23341718

Computational quantification of the cardiac energy consumption during intra-aortic balloon pumping using a cardiac electromechanics model.

PubMed

Lim, Ki Moo; Lee, Jeong Sang; Gyeong, Min-Soo; Choi, Jae-Sung; Choi, Seong Wook; Shim, Eun Bo

2013-01-01

To quantify the reduction in workload during intra-aortic balloon pump (IABP) therapy, indirect parameters are used, such as the mean arterial pressure during diastole, product of heart rate and peak systolic pressure, and pressure-volume area. Therefore, we investigated the cardiac energy consumption during IABP therapy using a cardiac electromechanics model. We incorporated an IABP function into a previously developed electromechanical model of the ventricle with a lumped model of the circulatory system and investigated the cardiac energy consumption at different IABP inflation volumes. When the IABP was used at inflation level 5, the cardiac output and stroke volume increased 11%, the ejection fraction increased 21%, the stroke work decreased 1%, the mean arterial pressure increased 10%, and the ATP consumption decreased 12%. These results show that although the ATP consumption is decreased significantly, stroke work is decreased only slightly, which indicates that the IABP helps the failed ventricle to pump blood efficiently.

Sarcospan Regulates Cardiac Isoproterenol Response and Prevents Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

PubMed

Parvatiyar, Michelle S; Marshall, Jamie L; Nguyen, Reginald T; Jordan, Maria C; Richardson, Vanitra A; Roos, Kenneth P; Crosbie-Watson, Rachelle H

2015-12-23

Duchenne muscular dystrophy is a fatal cardiac and skeletal muscle disease resulting from mutations in the dystrophin gene. We have previously demonstrated that a dystrophin-associated protein, sarcospan (SSPN), ameliorated Duchenne muscular dystrophy skeletal muscle degeneration by activating compensatory pathways that regulate muscle cell adhesion (laminin-binding) to the extracellular matrix. Conversely, loss of SSPN destabilized skeletal muscle adhesion, hampered muscle regeneration, and reduced force properties. Given the importance of SSPN to skeletal muscle, we investigated the consequences of SSPN ablation in cardiac muscle and determined whether overexpression of SSPN into mdx mice ameliorates cardiac disease symptoms associated with Duchenne muscular dystrophy cardiomyopathy. SSPN-null mice exhibited cardiac enlargement, exacerbated cardiomyocyte hypertrophy, and increased fibrosis in response to β-adrenergic challenge (isoproterenol; 0.8 mg/day per 2 weeks). Biochemical analysis of SSPN-null cardiac muscle revealed reduced sarcolemma localization of many proteins with a known role in cardiomyopathy pathogenesis: dystrophin, the sarcoglycans (α-, δ-, and γ-subunits), and β1D integrin. Transgenic overexpression of SSPN in Duchenne muscular dystrophy mice (mdx(TG)) improved cardiomyofiber cell adhesion, sarcolemma integrity, cardiac functional parameters, as well as increased expression of compensatory transmembrane proteins that mediate attachment to the extracellular matrix. SSPN regulates sarcolemmal expression of laminin-binding complexes that are critical to cardiac muscle function and protects against transient and chronic injury, including inherited cardiomyopathy. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Diagnostic accuracy and functional parameters of myocardial perfusion scintigraphy using accelerated cardiac acquisition with IQ SPECT technique in comparison to conventional imaging.

PubMed

Pirich, Christian; Keinrath, Peter; Barth, Gabriele; Rendl, Gundula; Rettenbacher, Lukas; Rodrigues, Margarida

2017-03-01

IQ SPECT consists of a new pinhole-like collimator, cardio-centric acquisition, and advanced 3D iterative SPECT reconstruction. The aim of this paper was to compare diagnostic accuracy and functional parameters obtained with IQ SPECT versus conventional SPECT in patients undergoing myocardial perfusion scintigraphy with adenosine stress and at rest. Eight patients with known or suspected coronary artery disease underwent [99mTc] tetrofosmin gated SPECT. Acquisition was performed on a Symbia T6 equipped with IQ SPECT and on a conventional gamma camera system. Gated SPECT data were used to calculate functional parameters. Scores analysis was performed on a 17-segment model. Coronary angiography and clinical follow-up were considered as diagnostic reference standard. Mean acquisition time was 4 minutes with IQ SPECT and 21 minutes with conventional SPECT. Agreement degree on the diagnostic accuracy between both systems was 0.97 for stress studies, 0.91 for rest studies and 0.96 for both studies. Perfusion abnormalities scores obtained by using IQ SPECT and conventional SPECT were not significant different: SSS, 9.7±8.8 and 10.1±6.4; SRS, 7.1±6.1 and 7.5±7.3; SDS, 4.0±6.1 and 3.9±4.3, respectively. However, a significant difference was found in functional parameters derived from IQ SPECT and conventional SPECT both after stress and at rest. Mean LVEF was 8% lower using IQ SPECT. Differences in LVEF were found in patients with normal LVEF and patients with reduced LVEF. Functional parameters using accelerated cardiac acquisition with IQ SPECT are significantly different to those obtained with conventional SPECT, while agreement for clinical interpretation of myocardial perfusion scintigraphy with both techniques is high.

Sexual Dimorphism in the Alterations of Cardiac Muscle Mitochondrial Bioenergetics Associated to the Ageing Process.

PubMed

Colom, Bartomeu; Oliver, Jordi; Garcia-Palmer, Francisco J

2015-11-01

The incidence of cardiac disease is age and sex dependent, but the mechanisms governing these associations remain poorly understood. Mitochondria are the organelles in charge of producing energy for the cells, and their malfunction has been linked to cardiovascular disease and heart failure. Interestingly, heart mitochondrial content and functionality are also age and sex dependent. Here we investigated the combinatory effects of age and sex in mitochondrial bioenergetics that could help to understand their role on cardiac disease. Cardiac mitochondria from 6- and 24-month-old male and female Wistar rats were isolated, and the enzymatic activities of the oxidative-phosphorylative complexes I, III, and IV and ATPase, as well as the protein levels of complex IV, β-ATPase, and mitochondrial transcription factor A (TFAM), were measured. Furthermore, heart DNA content, citrate synthase activity, mitochondrial protein content, oxygen consumption, and H2O2 generation were also determined. Results showed a reduction in heart mitochondrial mass and functionality with age that correlated with increased H2O2 generation. Moreover, sex-dependent differences were found in several of these parameters. In particular, old females exhibited a significant loss of mitochondrial function and increased relative H2O2 production compared with their male counterparts. The results demonstrate a sex dimorphism in the age-associated defects on cardiac mitochondrial function. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of obstructive sleep apnea and obesity on exercise function in children.

PubMed

Evans, Carla A; Selvadurai, Hiran; Baur, Louise A; Waters, Karen A

2014-06-01

Evaluate the relative contributions of weight status and obstructive sleep apnea (OSA) to cardiopulmonary exercise responses in children. Prospective, cross-sectional study. Participants underwent anthropometric measurements, overnight polysomnography, spirometry, cardiopulmonary exercise function testing on a cycle ergometer, and cardiac doppler imaging. OSA was defined as ≥ 1 obstructive apnea or hypopnea per hour of sleep (OAHI). The effect of OSA on exercise function was evaluated after the parameters were corrected for body mass index (BMI) z-scores. Similarly, the effect of obesity on exercise function was examined when the variables were adjusted for OAHI. Tertiary pediatric hospital. Healthy weight and obese children, aged 7-12 y. N/A. Seventy-one children were studied. In comparison with weight-matched children without OSA, children with OSA had a lower cardiac output, stroke volume index, heart rate, and oxygen consumption (VO2 peak) at peak exercise capacity. After adjusting for BMI z-score, children with OSA had 1.5 L/min (95% confidence interval -2.3 to -0.6 L/min; P = 0.001) lower cardiac output at peak exercise capacity, but minute ventilation and ventilatory responses to exercise were not affected. Obesity was only associated with physical deconditioning. Cardiac dysfunction was associated with the frequency of respiratory-related arousals, the severity of hypoxia, and heart rate during sleep. Children with OSA are exercise limited due to a reduced cardiac output and VO2 peak at peak exercise capacity, independent of their weight status. Comorbid OSA can further decrease exercise performance in obese children.

Impact of specific training and competition on myocardial structure and function in different age ranges of male handball players

PubMed Central

Agrebi, Brahim; Tkatchuk, Vladimir; Hlila, Nawel; Mouelhi, Emna; Belhani, Ali

2015-01-01

Handball activity involves cardiac changes and demands a mixture of both eccentric and concentric remodeling within the heart. This study seeks to explore heart performance and cardiac remodeling likely to define cardiac parameters which influence specific performance in male handball players across different age ranges. Forty three players, with a regular training and competitive background in handball separated into three groups aged on average 11.78±0.41 for youth players aka “schools”, “elite juniors” 15.99±0.81 and “elite adults” 24.46±2.63 years, underwent echocardiography and ECG examinations. Incremental ergocycle and specific field (SFT) tests have also been conducted. With age and regular training and competition, myocardial remodeling in different age ranges exhibit significant differences in dilatation’s parameters between “schools” and “juniors” players, such as the end-diastolic diameter (LVEDD) and the end-systolic diameter of the left ventricle (LVESD), the root of aorta (Ao) and left atrial (LA), while significant increase is observed between “juniors” and “adults” players in the interventricular septum (IVS), the posterior wall thicknesses (PWT) and LV mass index. ECG changes are also noted but NS differences were observed in studied parameters. For incremental maximal test, players demonstrate a significant increase in duration and total work between “schools” and “juniors” and, in total work only, between “juniors” and “seniors”. The SFT shows improvement in performance which ranged between 26.17±1.83 sec to 31.23±2.34 sec respectively from “seniors” to “schools”. The cross-sectional approach used to compare groups with prior hypothesis that there would be differences in exercise performance and cardiac parameters depending on duration of prior handball practice, leads to point out the early cardiac remodeling within the heart as adaptive change. Prevalence of cardiac chamber dilation with less hypertrophy remodeling was found from “schools” to “juniors” while a prevalence of cardiac hypertrophy with less pronounced chamber dilation remodeling was noted later. PMID:26630561

Ablation of the Right Cardiac Vagus Nerve Reduces Acetylcholine Content without Changing the Inflammatory Response during Endotoxemia.

PubMed

Plaschke, Konstanze; Do, Thuc Quyen Monica; Uhle, Florian; Brenner, Thorsten; Weigand, Markus A; Kopitz, Jürgen

2018-02-01

Acetylcholine is the main transmitter of the parasympathetic vagus nerve. According to the cholinergic anti-inflammatory pathway (CAP) concept, acetylcholine has been shown to be important for signal transmission within the immune system and also for a variety of other functions throughout the organism. The spleen is thought to play an important role in regulating the CAP. In contrast, the existence of a "non-neuronal cardiac cholinergic system" that influences cardiac innervation during inflammation has been hypothesized, with recent publications introducing the heart instead of the spleen as a possible interface between the immune and nervous systems. To prove this hypothesis, we investigated whether selectively disrupting vagal stimulation of the right ventricle plays an important role in rat CAP regulation during endotoxemia. We performed a selective resection of the right cardiac branch of the Nervus vagus (VGX) with a corresponding sham resection in vehicle-injected and endotoxemic rats. Rats were injected with lipopolysaccharide (LPS, 1 mg/kg body weight, intravenously) and observed for 4 h. Intraoperative blood gas analysis was performed, and hemodynamic parameters were assessed using a left ventricular pressure-volume catheter. Rat hearts and blood were collected, and the expression and concentration of proinflammatory cytokines using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were measured, respectively. Four hours after injection, LPS induced a marked deterioration in rat blood gas parameters such as pH value, potassium, base excess, glucose, and lactate. The mean arterial blood pressure and the end-diastolic volume had decreased significantly. Further, significant increases in blood cholinesterases and in proinflammatory (IL-1β, IL-6, TNF-α) cytokine concentration and gene expression were obtained. Right cardiac vagus nerve resection (VGX) led to a marked decrease in heart acetylcholine concentration and an increase in cardiac acetylcholinesterase activity. Without LPS, VGX changed rat hemodynamic parameters, including heart frequency, cardiac output, and end-diastolic volume. In contrast, VGX during endotoxemia did not significantly change the concentration and expression of proinflammatory cytokines in the heart. In conclusion we demonstrate that right cardiac vagal innervation regulates cardiac acetylcholine content but neither improves nor worsens systemic inflammation.

Ablation of the Right Cardiac Vagus Nerve Reduces Acetylcholine Content without Changing the Inflammatory Response during Endotoxemia

PubMed Central

Plaschke, Konstanze; Do, Thuc Quyen Monica; Brenner, Thorsten; Weigand, Markus A.; Kopitz, Jürgen

2018-01-01

Acetylcholine is the main transmitter of the parasympathetic vagus nerve. According to the cholinergic anti-inflammatory pathway (CAP) concept, acetylcholine has been shown to be important for signal transmission within the immune system and also for a variety of other functions throughout the organism. The spleen is thought to play an important role in regulating the CAP. In contrast, the existence of a “non-neuronal cardiac cholinergic system” that influences cardiac innervation during inflammation has been hypothesized, with recent publications introducing the heart instead of the spleen as a possible interface between the immune and nervous systems. To prove this hypothesis, we investigated whether selectively disrupting vagal stimulation of the right ventricle plays an important role in rat CAP regulation during endotoxemia. We performed a selective resection of the right cardiac branch of the Nervus vagus (VGX) with a corresponding sham resection in vehicle-injected and endotoxemic rats. Rats were injected with lipopolysaccharide (LPS, 1 mg/kg body weight, intravenously) and observed for 4 h. Intraoperative blood gas analysis was performed, and hemodynamic parameters were assessed using a left ventricular pressure-volume catheter. Rat hearts and blood were collected, and the expression and concentration of proinflammatory cytokines using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were measured, respectively. Four hours after injection, LPS induced a marked deterioration in rat blood gas parameters such as pH value, potassium, base excess, glucose, and lactate. The mean arterial blood pressure and the end-diastolic volume had decreased significantly. Further, significant increases in blood cholinesterases and in proinflammatory (IL-1β, IL-6, TNF-α) cytokine concentration and gene expression were obtained. Right cardiac vagus nerve resection (VGX) led to a marked decrease in heart acetylcholine concentration and an increase in cardiac acetylcholinesterase activity. Without LPS, VGX changed rat hemodynamic parameters, including heart frequency, cardiac output, and end-diastolic volume. In contrast, VGX during endotoxemia did not significantly change the concentration and expression of proinflammatory cytokines in the heart. In conclusion we demonstrate that right cardiac vagal innervation regulates cardiac acetylcholine content but neither improves nor worsens systemic inflammation. PMID:29389905

Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest

PubMed Central

Mills, Richard J.; Titmarsh, Drew M.; Koenig, Xaver; Parker, Benjamin L.; Ryall, James G.; Quaife-Ryan, Gregory A.; Voges, Holly K.; Hodson, Mark P.; Ferguson, Charles; Drowley, Lauren; Plowright, Alleyn T.; Needham, Elise J.; Wang, Qing-Dong; Gregorevic, Paul; Xin, Mei; Thomas, Walter G.; Parton, Robert G.; Nielsen, Lars K.; Elliott, David A.; Porrello, Enzo R.

2017-01-01

The mammalian heart undergoes maturation during postnatal life to meet the increased functional requirements of an adult. However, the key drivers of this process remain poorly defined. We are currently unable to recapitulate postnatal maturation in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), limiting their potential as a model system to discover regenerative therapeutics. Here, we provide a summary of our studies, where we developed a 96-well device for functional screening in human pluripotent stem cell-derived cardiac organoids (hCOs). Through interrogation of >10,000 organoids, we systematically optimize parameters, including extracellular matrix (ECM), metabolic substrate, and growth factor conditions, that enhance cardiac tissue viability, function, and maturation. Under optimized maturation conditions, functional and molecular characterization revealed that a switch to fatty acid metabolism was a central driver of cardiac maturation. Under these conditions, hPSC-CMs were refractory to mitogenic stimuli, and we found that key proliferation pathways including β-catenin and Yes-associated protein 1 (YAP1) were repressed. This proliferative barrier imposed by fatty acid metabolism in hCOs could be rescued by simultaneous activation of both β-catenin and YAP1 using genetic approaches or a small molecule activating both pathways. These studies highlight that human organoids coupled with higher-throughput screening platforms have the potential to rapidly expand our knowledge of human biology and potentially unlock therapeutic strategies. PMID:28916735

Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction.

PubMed

Rodrigues, Bruno; Jorge, Luciana; Mostarda, Cristiano T; Rosa, Kaleizu T; Medeiros, Alessandra; Malfitano, Christiane; de Souza, Alcione L; Viegas, Katia Aparecida da Silva; Lacchini, Silvia; Curi, Rui; Brum, Patricia C; De Angelis, Kátia; Irigoyen, Maria Cláudia

2012-09-01

Exercise training (ET) has been used as a nonpharmacological strategy for treatment of diabetes and myocardial infarction (MI) separately. We evaluated the effects ET on functional and molecular left ventricular (LV) parameters as well as on autonomic function and mortality in diabetics after MI. Male Wistar rats were divided into control (C), sedentary-diabetic infarcted (SDI), and trained-diabetic infarcted (TDI) groups. MI was induced after 15 days of streptozotocin-diabetes induction. Seven days after MI, the trained group underwent ET protocol (90 days, 50-70% maximal oxygen consumption-VO(2)max). LV function was evaluated noninvasively and invasively; baroreflex sensitivity, pulse interval variability, cardiac output, tissue blood flows, VEGF mRNA and protein, HIF1-α mRNA, and Ca(2+) handling proteins were measured. MI area was reduced in TDI (21 ± 4%) compared with SDI (38 ± 4%). ET induced improvement in cardiac function, hemodynamics, and tissue blood flows. These changes were probable consequences of a better expression of Ca(2+) handling proteins, increased VEGF mRNA and protein expression as well as improvement in autonomic function, that resulted in reduction of mortality in TDI (33%) compared with SDI (68%) animals. ET reduced cardiac and peripheral dysfunction and preserved autonomic control in diabetic infarcted rats. Consequently, these changes resulted in improved VO(2)max and survival after MI. Copyright © 2012 Elsevier Inc. All rights reserved.

Left ventricular eccentricity index measured with SPECT myocardial perfusion imaging: An additional parameter of adverse cardiac remodeling.

PubMed

Gimelli, Alessia; Liga, Riccardo; Clemente, Alberto; Marras, Gavino; Kusch, Annette; Marzullo, Paolo

2017-01-12

Single-photon emission computed-tomography (SPECT) allows the quantification of LV eccentricity index (EI), a measure of cardiac remodeling. We sought to evaluate the feasibility of EI measurement with SPECT myocardial perfusion imaging and its interactions with relevant LV functional and structural parameters. Four-hundred and fifty-six patients underwent myocardial perfusion imaging on a Cadmium-Zinc-Telluride (CZT) camera. The summed rest, stress, and difference scores were calculated. From rest images, the LV end-diastolic (EDV) and end-systolic volumes, ejection fraction (EF), and peak filling rate (PFR) were calculated. In every patient, the EI, ranging from 0 (sphere) to 1 (line), was computed using a dedicated software (QGS/QPS; Cedars-Sinai Medical Center). Three-hundred and thirty-eight/456 (74%) patients showed a normal EF (>50%), while 26% had LV systolic dysfunction. The EI was computed from CZT images with excellent reproducibility (interclass correlation coefficient: 0.99, 95% CI 0.98-0.99). More impaired EI values correlated with the presence of a more abnormal LV perfusion (P < .001), function (EF and PFR, P < .001), and structure (EDV, P < .001). On multivariate analysis, higher EDV (P < .001) and depressed EF (P = .014) values were independent predictors of abnormal EI. The evaluation of LV eccentricity is feasible on gated CZT images. Abnormal EI associates with significant cardiac structural and functional abnormalities.

Influence of the low thyroid state in diabetes mellitus on cardiac function and inotropic responsiveness to alpha 1-adrenoceptor stimulation: comparison with the role of hypothyroidism alone.

PubMed

Beenen, O H; Pfaffendorf, M; van Zwieten, P A

1996-10-01

The hypothyroid state accompanying diabetes mellitus has been suggested to be partly responsible for the diabetes-induced metabolic, hemodynamic, and pharmacological cardiovascular changes. We assessed the effectivity of streptozotocin (STZ) to induce diabetes mellitus and a hypothyroid state. Furthermore, we investigated the influence of diabetes and hypothyrodism on cardiac function and the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline in isolated perfused hearts. Fasted or nonfasted Wistar rats were made diabetic with STZ 20, 40 or 60 mg/kg intravenously (i.v.). Another group was made hypothyroid by addition of 6-n-propyl-2-thiouracil (PTU) to their drinking water. Rats receiving PTU became hypothyroid, whereas rats receiving STZ became simultaneously diabetic and hypothyroid. Basal functional parameters obtained in isolated perfused hearts were not influenced by diabetes, whereas maximal contractility was reduced in hearts obtained from hypothyroid animals. Cardiac inotropic responses to cirazoline were increased in diabetic rats, whereas responses in hypothyroid rats were not different from those in hearts obtained from control animals. Although diabetes mellitus and hypothyroidism are associated with various similar metabolic and haemodynamic parameters, the increased inotropic response to alpha 1-adrenoceptor stimulation as observed in isolated perfused hearts of diabetic rats cannot be explained by the decrease in serum thyroxine levels.

Cardiovascular autonomic dysfunction and carotid stiffness in adults with repaired tetralogy of Fallot.

PubMed

Novaković, Marko; Prokšelj, Katja; Starc, Vito; Jug, Borut

2017-06-01

Adults after surgical repair of tetralogy of Fallot (ToF) may have impaired vascular and cardiac autonomic function. Thus, we wanted to assess interrelations between heart rate variability (HRV) and heart rate recovery (HRR), as parameters of cardiac autonomic function, and arterial stiffness, as a parameter of vascular function, in adults with repaired ToF as compared to healthy controls. In a case-control study of adults with repaired ToF and healthy age-matched controls we measured: 5-min HRV variability (with time and frequency domain data collected), carotid artery stiffness (through pulse-wave analysis using echo-tracking ultrasound) and post-exercise HRR (cycle ergometer exercise testing). Twenty-five patients with repaired ToF (mean age 38 ± 10 years) and 10 healthy controls (mean age 39 ± 8 years) were included. Selected HRR and HRV (time-domain) parameters, but not arterial stiffness were significantly reduced in adults after ToF repair. Moreover, a strong association between late/slow HRR (after 2, 3 and 4 min) and carotid artery stiffness was detected in ToF patients (r = -0.404, p = 0.045; r = -0.545, p = 0.005 and r = -0.545, p = 0.005, respectively), with statistical significance retained even after adjusting for age, gender, resting heart rate and β-blockers use (r = -0.393, p = 0.024 for HRR after 3 min). Autonomic cardiac function is impaired in patients with repaired ToF, and independently associated with vascular function in adults after ToF repair, but not in age-matched healthy controls. These results might help in introducing new predictors of cardiovascular morbidity in a growing population of adults after surgical repair of ToF.

Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography

PubMed Central

Li, Airong; Ahsen, Osman O.; Liu, Jonathan J.; Du, Chuang; McKee, Mary L.; Yang, Yan; Wasco, Wilma; Newton-Cheh, Christopher H.; O'Donnell, Christopher J.; Fujimoto, James G.; Zhou, Chao; Tanzi, Rudolph E.

2013-01-01

The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits. PMID:23696452

Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography.

PubMed

Li, Airong; Ahsen, Osman O; Liu, Jonathan J; Du, Chuang; McKee, Mary L; Yang, Yan; Wasco, Wilma; Newton-Cheh, Christopher H; O'Donnell, Christopher J; Fujimoto, James G; Zhou, Chao; Tanzi, Rudolph E

2013-09-15

The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits.

Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model.

PubMed

Daltro, P S; Barreto, B C; Silva, P G; Neto, P Chenaud; Sousa Filho, P H F; Santana Neta, D; Carvalho, G B; Silva, D N; Paredes, B D; de Alcantara, A C; Freitas, L A R; Couto, R D; Santos, R R; Souza, B S F; Soares, M B P; Macambira, S G

2017-10-01

Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity. After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated. Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis. Characterization of CM by protein array showed the presence of different cytokines and growth factors, including chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I, adiponectin, transforming growth factor (TGF) β, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis. Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due to obesity and corroborate to the paracrine action of MSCs in heart disease models. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome).

PubMed

Feinberg, M S; Scheinowitz, M; Laron, Z

2000-01-15

Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.

Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine

PubMed Central

Faller, Kiterie M E; Atzler, Dorothee; McAndrew, Debra J; Zervou, Sevasti; Whittington, Hannah J; Simon, Jillian N; Aksentijevic, Dunja; ten Hove, Michiel; Choe, Chi-un; Isbrandt, Dirk; Casadei, Barbara; Schneider, Jurgen E; Neubauer, Stefan; Lygate, Craig A

2018-01-01

Abstract Aims Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality. Methods and results Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function. Conclusions Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases. PMID:29236952

Enhancing ejection fraction measurement through 4D respiratory motion compensation in cardiac PET imaging

NASA Astrophysics Data System (ADS)

Tang, Jing; Wang, Xinhui; Gao, Xiangzhen; Segars, W. Paul; Lodge, Martin A.; Rahmim, Arman

2017-06-01

ECG gated cardiac PET imaging measures functional parameters such as left ventricle (LV) ejection fraction (EF), providing diagnostic and prognostic information for management of patients with coronary artery disease (CAD). Respiratory motion degrades spatial resolution and affects the accuracy in measuring the LV volumes for EF calculation. The goal of this study is to systematically investigate the effect of respiratory motion correction on the estimation of end-diastolic volume (EDV), end-systolic volume (ESV), and EF, especially on the separation of normal and abnormal EFs. We developed a respiratory motion incorporated 4D PET image reconstruction technique which uses all gated-frame data to acquire a motion-suppressed image. Using the standard XCAT phantom and two individual-specific volunteer XCAT phantoms, we simulated dual-gated myocardial perfusion imaging data for normally and abnormally beating hearts. With and without respiratory motion correction, we measured the EDV, ESV, and EF from the cardiac-gated reconstructed images. For all the phantoms, the estimated volumes increased and the biases significantly reduced with motion correction compared with those without. Furthermore, the improvement of ESV measurement in the abnormally beating heart led to better separation of normal and abnormal EFs. The simulation study demonstrated the significant effect of respiratory motion correction on cardiac imaging data with motion amplitude as small as 0.7 cm. The larger the motion amplitude the more improvement respiratory motion correction brought about on the EF measurement. Using data-driven respiratory gating, we also demonstrated the effect of respiratory motion correction on estimating the above functional parameters from list mode patient data. Respiratory motion correction has been shown to improve the accuracy of EF measurement in clinical cardiac PET imaging.

Intestinal congestion and right ventricular dysfunction: a link with appetite loss, inflammation, and cachexia in chronic heart failure.

PubMed

Valentova, Miroslava; von Haehling, Stephan; Bauditz, Juergen; Doehner, Wolfram; Ebner, Nicole; Bekfani, Tarek; Elsner, Sebastian; Sliziuk, Veronika; Scherbakov, Nadja; Murín, Ján; Anker, Stefan D; Sandek, Anja

2016-06-01

Mechanisms leading to cachexia in heart failure (HF) are not fully understood. We evaluated signs of intestinal congestion in patients with chronic HF and their relationship with cachexia. Of the 165 prospectively enrolled outpatients with left ventricular ejection fraction ≤40%, 29 (18%) were cachectic. Among echocardiographic parameters, the combination of right ventricular dysfunction and elevated right atrial pressure (RAP) provided the best discrimination between cachectic and non-cachectic patients [area under the curve 0.892, 95% confidence interval (CI): 0.832-0.936]. Cachectic patients, compared with non-cachectic, had higher prevalence of postprandial fullness, appetite loss, and abdominal discomfort. Abdominal ultrasound showed a larger bowel wall thickness (BWT) in the entire colon and terminal ileum in cachectic than in non-cachectic patients. Bowel wall thickness correlated positively with gastrointestinal symptoms, high-sensitivity C-reactive protein, RAP, and truncal fat-free mass, the latter serving as a marker of the fluid content. Logistic regression analysis showed that BWT was associated with cachexia, even after adjusting for cardiac function, inflammation, and stages of HF (odds ratio 1.4, 95% CI: 1.0-1.8; P-value = 0.03). Among the cardiac parameters, only RAP remained significantly associated with cachexia after multivariable adjustment. Cardiac cachexia was associated with intestinal congestion irrespective of HF stage and cardiac function. Gastrointestinal discomfort, appetite loss, and pro-inflammatory activation provide probable mechanisms, by which intestinal congestion may trigger cardiac cachexia. However, our results are preliminary and larger studies are needed to clarify the intrinsic nature of this relationship. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Evaluation of autonomic functions of patients with multiple system atrophy and Parkinson's disease by head-up tilt test.

PubMed

Watano, Chikako; Shiota, Yuri; Onoda, Keiichi; Sheikh, Abdullah Md; Mishima, Seiji; Nitta, Eri; Yano, Shozo; Yamaguchi, Shuhei; Nagai, Atsushi

2018-02-01

The aim of this study was to evaluate the autonomic neural function in Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test and spectral analysis of cardiovascular parameters. This study included 15 patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects. High frequency power of the RR interval (RR-HF), the ratio of low frequency power of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively. Both patients with PD and MSA showed orthostatic hypotension and lower parasympathetic function (RR-HF) at tilt position as compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was significantly high in patients with PD than MSA at supine position. RR-LF/HF tended to increase in MSA and HC, but decreased in PD by tilting. Consequently, the change of the ratio due to tilting (ΔRR-LF/HF) was significantly lower in patients with PD than in HC subjects. Further analysis showed that compared to mild stage of PD, RR-LF/HF at the supine position was significantly higher in advanced stage. By tilting, it was increased in mild stage and decreased in the advanced stage of PD, causing ΔRR-LF/HF to decrease significantly in the advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular parameters is useful to identify sympathetic and parasympathetic disorders in MSA and PD. High cardiac sympathetic function at the supine position, and its reduction by tilting might be a characteristic feature of PD, especially in the advanced stage.

Automatic segmentation of the left ventricle in a cardiac MR short axis image using blind morphological operation

NASA Astrophysics Data System (ADS)

Irshad, Mehreen; Muhammad, Nazeer; Sharif, Muhammad; Yasmeen, Mussarat

2018-04-01

Conventionally, cardiac MR image analysis is done manually. Automatic examination for analyzing images can replace the monotonous tasks of massive amounts of data to analyze the global and regional functions of the cardiac left ventricle (LV). This task is performed using MR images to calculate the analytic cardiac parameter like end-systolic volume, end-diastolic volume, ejection fraction, and myocardial mass, respectively. These analytic parameters depend upon genuine delineation of epicardial, endocardial, papillary muscle, and trabeculations contours. In this paper, we propose an automatic segmentation method using the sum of absolute differences technique to localize the left ventricle. Blind morphological operations are proposed to segment and detect the LV contours of the epicardium and endocardium, automatically. We test the benchmark Sunny Brook dataset for evaluation of the proposed work. Contours of epicardium and endocardium are compared quantitatively to determine contour's accuracy and observe high matching values. Similarity or overlapping of an automatic examination to the given ground truth analysis by an expert are observed with high accuracy as with an index value of 91.30% . The proposed method for automatic segmentation gives better performance relative to existing techniques in terms of accuracy.

Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.

PubMed

Feng, Qiaoli; Lu, Chengzhi; Wang, Li; Song, Lijun; Li, Chao; Uppada, Ravi Chandra

2017-02-17

This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action. Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47 phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively. We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47 phox ,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0.092 and 0.931, respectively). Importantly, the expression of TH, AngII and Ang(1-7) was positively correlated with MDA and negatively correlated with SOD. Between-group comparisons demonstrated no differences in serum creatinine (P = 0.706). RDN attenuated cardiac remodelling and improved heart function by decreasing the level of cardiac oxidative stress and the local activity of the SNS and RAS in cardiac tissues. Additionally, the safety of the RDN procedure was established, as no significant decrease in LVSP or rise in serum creatinine was observed in our study.

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

PubMed

Badano, Luigi P; Miglioranza, Marcelo H; Edvardsen, Thor; Colafranceschi, Alexandre Siciliano; Muraru, Denisa; Bacal, Fernando; Nieman, Koen; Zoppellaro, Giacomo; Marcondes Braga, Fabiana G; Binder, Thomas; Habib, Gilbert; Lancellotti, Patrizio

2015-09-01

The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold-standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Cardiac autonomic profile in different sports disciplines during all-day activity.

PubMed

Sztajzel, J; Jung, M; Sievert, K; Bayes De Luna, A

2008-12-01

Physical training and sport activity have a beneficial effect on cardiac autonomic activity. However, the exact impact of different types of sports disciplines on cardiac autonomic function is still unclear. The aim of this study was to evaluate the cardiac autonomic profile in different sports discplines and to determine their impact on cardiac autonomic function by using heart rate variability (HRV), a noninvasive electrocardiographic (ECG) analysis of the sympatho-vagal balance. Temporal and spectral HRV parameters determined from 24-hour continuous ECG monitoring were studied in 40 subjects, including 12 endurance athletes, 14 hockey players and 14 untrained male volunteers (control group). Each participant had to wear a Holter recorder during 24 hours and to continue his everyday activities. All HRV parameters were compared between the 3 study groups. All heart rate values were lower and all parasympathetic-related time domain indices, including root mean square of successive differences (RMSSD) and pNN50 (NN50 count divided by the total number of all NN intervals), were higher in both athletes groups as compared with controls (P<0.05). However, standard deviation of all NN intervals (SDNN) values, which determine global HRV, were significantly higher only in endurance athletes (P<0.05). Furthermore, the power spectral components low frequency (LF), a mixture of both autonomic inputs, and HF (high frequency), a marker of vagal modulation, were significantly higher with a resulting lower LF/HF ratio in both athletes groups as compared to controls (P<0.05). Both endurance and team playing athletic activity induce during all-day a high parasympathetic tone (higher RMSSD, pNN50 and HF, and lower LF/HF ratio). However, only endurance athletic activity has a particularly high global HRV (higher SDNN), indicating thereby that this type sports discipline may have a more substantially favorable effect on the cardiac autonomic profile.

EFFECTS OF RESIDUAL OIL FLY ASH ON CARDIAC, PULMONARY, AND THERMOREGULATORY PARAMETERS IN RATS

EPA Science Inventory

Epidemiological studies have associated ambient levels of particulate matter (PM) with the incidence of cardiopulmonary morbidity and mortality. Additionally, elevated levels of PM have been associated with reduced lung function. More recent published data have suggested a relati...

Effect of dobutamine on extravascular lung water index, ventilator function, and perfusion parameters in acute respiratory distress syndrome associated with septic shock.

PubMed

Zhou, Min; Dai, Ji; Du, Min; Wang, Wei; Guo, Changxing; Wang, Yi; Tang, Rui; Xu, Fengling; Rao, Zhuqing; Sun, Gengyun

2016-08-01

The role of dobutamine in the relief of pulmonary edema during septic shock-induced acute respiratory distress syndrome (ARDS) remains undetermined, due to a lack of controllable and quantitative clinical studies. Our objective was to assess the potential effects of dobutamine on extravascular lung water index (ELWI) in septic shock-induced ARDS, reflecting its importance in pulmonary edema. At the same time, ventilator function and perfusion parameters were evaluated. We designed a prospective, non-randomized, non-blinded, controlled study to compare the differences in PiCCO parameters after 6 h of constant dobutamine infusion (15 μg/kg/min), in the baseline parameters in 26 septic shock-related ARDS patients with cardiac index ≥ 2.5I/min/m(2) and hyperlactatemia. These patients (12 survivors/14 non-survivors) were monitored using the PiCCO catheter system within 48 h of onset of septic shock. The dynamic changes in ELWI, which is typically used for quantifying the extent of pulmonary edema, were evaluated, and the corresponding ventilator function and tissue perfusion parameters were also measured. Decreasing ELWI (p = 0.0376) was accompanied by significantly decreased SVRI (p < 0.0001). Despite a significant increase in cardiac output (p < 0.0001), no differences were found in ITBI or GEDI. Moreover, the required dose of norepinephrine was decreased (p = 0.0389), and urine output was increased (p = 0.0358), accompanied by stabilized lactacidemia and MAP. Additionally, airway pressure was moderately improved. During the early stage of septic shock-induced ARDS, dobutamine treatment demonstrated a beneficial effect by relieving pulmonary edema in patients, without a negative elevation in preload or hemodynamics, which might account for the improvements in ventilator function and tissue hypoperfusion.

Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

PubMed

Francomano, D; Bruzziches, R; Barbaro, G; Lenzi, A; Aversa, A

2014-04-01

Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body composition improvements attained.

Cardiorespiratory Fitness and Cardiac Autonomic Function in Diabetes.

PubMed

Röhling, Martin; Strom, Alexander; Bönhof, Gidon J; Roden, Michael; Ziegler, Dan

2017-10-23

This review summarizes the current knowledge on the relationship of physical activity, exercise, and cardiorespiratory fitness (CRF) with cardiovascular autonomic neuropathy (CAN) based on epidemiological, clinical, and interventional studies. The prevalence of CAN increases with age and duration of diabetes. Further risk factors for CAN comprise poor glycemic control, dyslipidemia, abdominal obesity, hypertension, and the presence of diabetic complications. CAN has been also linked to reduced CRF. We recently showed that CRF parameters (e.g., maximal oxidative capacity or oxidative capacity at the anaerobic threshold) are associated with cardiac autonomic function in patients recently diagnosed with type 1 or type 2 diabetes. Exercise interventions have shown that physical activity can increase cardiovagal activity and reduce sympathetic overactivity. In particular, long-term and regularly, but also supervised, performed endurance and high-intense and high-volume exercise improves cardiac autonomic function in patients with type 2 diabetes. By contrast, the evidence in those with type 1 diabetes and also in individuals with prediabetes or metabolic syndrome is weaker. Overall, the studies reviewed herein addressing the question whether favorably modulating the autonomic nervous system may improve CRF during exercise programs support the therapeutic concept to promote physical activity and to achieve physical fitness. However, high-quality exercise interventions, especially in type 1 diabetes and metabolic syndrome including prediabetes, are further required to better understand the relationship between physical activity, fitness, and cardiac autonomic function.

The effects of the modulation of NMDA receptors by homocysteine thiolactone and dizocilpine on cardiodynamics and oxidative stress in isolated rat heart.

PubMed

Srejovic, Ivan; Jakovljevic, Vladimir; Zivkovic, Vladimir; Barudzic, Nevena; Radovanovic, Ana; Stanojlovic, Olivera; Djuric, Dragan M

2015-03-01

In light of the limited data concerning the role of N-methyl-D-aspartate (NMDA) receptors in cardiac function, the aim of the present study was to determine the role of NMDA receptors in cardiac function, as well as the possible role played by the oxidative stress induced by the overstimulation of NMDA receptors in isolated rat heart. The hearts of male, Wistar albino rats (n = 24, 12 in each experimental group, BM 180-200 g) were retrogradely perfused at a constant perfusion pressure (70 cm H₂O₂), using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent administration of DL-homocysteine thiolactone (DL-Hcy TLHC) alone, the combination of DL-Hcy TLHC and dizocilpine (MK-801), and MK-801 alone. In the second experimental group, the order of the administration of each of the substances was reversed. The oxidative stress biomarkers, including thiobarbituric acid reactive substances (TBARS), NO(2)(-), O(2)(-) and H₂O₂, were each determined spectrophotometrically. DL-Hcy TLHC and MK-801 depressed cardiac function. DL-Hcy TLHC decreased oxidative stress, a finding that contrasted with the results of the experiments in which MK-801 was administered first. The findings of this study were suggestive of the likely role played by NMDA receptors in the regulation of cardiac function and coronary circulation in isolated rat heart.

[Cardiac rhythm variability as an index of vegetative heart regulation in a situation of psychoemotional tension].

PubMed

Revina, N E

2006-01-01

Differentiated role of segmental and suprasegmental levels of cardiac rhythm variability regulation in dynamics of motivational human conflict was studied for the first time. The author used an original method allowing simultaneous analysis of psychological and physiological parameters of human activity. The study demonstrates that will and anxiety, as components of motivational activity spectrum, form the "energetic" basis of voluntary-constructive and involuntary-affective behavioral strategies, selectively uniting various levels of suprasegmental and segmental control of human heart functioning in a conflict situation.

Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males.

PubMed

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1997-12-01

Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

Interobserver agreement on the echocardiographic parameters that estimate right ventricular systolic function in the early postoperative period of cardiac surgery.

PubMed

Olmos-Temois, S G; Santos-Martínez, L E; Álvarez-Álvarez, R; Gutiérrez-Delgado, L G; Baranda-Tovar, F M

2016-11-01

To know the variability of transthoracic echocardiographic parameters that assess right ventricular systolic function by analyzing interobserver agreement in the early postoperative period of cardiovascular surgery. To assess the feasibility of these echocardiographic measurements. A cross-sectional study, double-blind pilot study was carried out from May 2011 to February 2013. Cardiovascular postoperative critical care at the National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico. Consecutive, non-probabilistic sampling. Fifty-six patients were studied in the postoperative period of cardiac surgery. The first echocardiographic parameters were obtained between 6-8hours after cardiac surgery, followed by blinded second measurements. Tricuspid annular plane systolic excursion (TAPSE), tricuspid annular peak systolic velocity on tissue Doppler imaging (VSPAT), diameters and right ventricular outflow area, tract fractional shortening. The agreement was analyzed by the Bland-Altman method, and its magnitude was assessed by the intraclass correlation coefficient (95% confidence interval). Both observers evaluated TAPSE and VSPAT in 48 patients (92%). The average TAPSE was 11.68±4.53mm (range 4-27mm). Right ventricular systolic dysfunction was observed in 41 cases (85%) and normal TAPSE in 7 patients (15%). The average difference and its limits according to TAPSE were -0.917±2.95 (-6.821, 4.988), with a magnitude of 0.725 (0.552, 0.837); the tricuspid annular peak systolic velocity on tissue Doppler imaging was -0.001±0.015 (-0.031, 0.030), and its magnitude 0.825 (0.708, 0.898), respectively. VSPAT and TAPSE were estimated by both observers in 92% of the patients, these parameters exhibiting the lowest interobserver variability. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Impact of metoprolol treatment on cardiac function and exercise tolerance in heart failure patients with neuropsychiatric disorders.

PubMed

Huang, Jingjing; Zhang, Ran; Liu, Xuelu; Meng, Yong

2018-01-01

To investigate the impact of neuropsychiatric disorders on the effect of metoprolol on cardiac and motor function in chronic heart failure (CHF) patients. From February 2013 to April 2016, CHF patients with clinical mental disorders received metoprolol (23.75 or 47.5 mg, once daily, orally) at the Second Affiliated Hospital of Kunming Medical University. Mental status was confirmed by means of the Hospital Anxiety and Depression Scale (HADS) and the Copenhagen Burnout Inventory (CBI) scale. Cardiac function parameters such as systolic blood pressure (SBP), ejection fraction (EF) and cardiac index (CI) as well as motor function including the 6 meter walk test (6MWT) and the Veteran's Specific Activity Questionnaire (VSAQ) were assessed as primary outcomes of the study. A total of 154 patients (median age, 66.39 years; men, n = 101) were allocated into eight groups based on their mental status. There were no significant differences in heart rate (HR) or SBP control achieved by metoprolol in any groups compared with the control (patients with normal mental status). Furthermore, biphasic ejection fraction (EF) changes were observed in all the groups with a decrease in the first month and increase from the sixth month. However, this increase was significantly lower (p < .001) than the EF achieved with metoprolol treatment in the control group except for the anxiety group. A similar pattern was seen for CI, 6MWT and VSAQ changes in all the groups. Patients in the anxiety group responded similarly to the patients with normal mental status. Depressive and high burnout symptoms, but not anxiety, lower the improvement of cardiac and motor function by metoprolol treatment in CHF.

Effects of Obstructive Sleep Apnea and Obesity on Exercise Function in Children

PubMed Central

Evans, Carla A.; Selvadurai, Hiran; Baur, Louise A.; Waters, Karen A.

2014-01-01

Study Objectives: Evaluate the relative contributions of weight status and obstructive sleep apnea (OSA) to cardiopulmonary exercise responses in children. Design: Prospective, cross-sectional study. Participants underwent anthropometric measurements, overnight polysomnography, spirometry, cardiopulmonary exercise function testing on a cycle ergometer, and cardiac doppler imaging. OSA was defined as ≥ 1 obstructive apnea or hypopnea per hour of sleep (OAHI). The effect of OSA on exercise function was evaluated after the parameters were corrected for body mass index (BMI) z-scores. Similarly, the effect of obesity on exercise function was examined when the variables were adjusted for OAHI. Setting: Tertiary pediatric hospital. Participants: Healthy weight and obese children, aged 7–12 y. Interventions: N/A. Measurements and Results: Seventy-one children were studied. In comparison with weight-matched children without OSA, children with OSA had a lower cardiac output, stroke volume index, heart rate, and oxygen consumption (VO2 peak) at peak exercise capacity. After adjusting for BMI z-score, children with OSA had 1.5 L/min (95% confidence interval -2.3 to -0.6 L/min; P = 0.001) lower cardiac output at peak exercise capacity, but minute ventilation and ventilatory responses to exercise were not affected. Obesity was only associated with physical deconditioning. Cardiac dysfunction was associated with the frequency of respiratory-related arousals, the severity of hypoxia, and heart rate during sleep. Conclusions: Children with OSA are exercise limited due to a reduced cardiac output and VO2 peak at peak exercise capacity, independent of their weight status. Comorbid OSA can further decrease exercise performance in obese children. Citation: Evans CA, Selvadurai H, Baur LA, Waters KA. Effects of obstructive sleep apnea and obesity on exercise function in children. SLEEP 2014;37(6):1103-1110. PMID:24882905

Pacsin 2 is required for the maintenance of a normal cardiac function in the developing mouse heart.

PubMed

Semmler, Judith; Kormann, Jan; Srinivasan, Sureshkumar Perumal; Köster, Annette; Sälzer, Daniel; Reppel, Michael; Hescheler, Jürgen; Plomann, Markus; Nguemo, Filomain

2018-02-01

The Pacsin proteins (Pacsin 1, 2 and 3) play an important role in intracellular trafficking and thereby signal transduction in many cells types. This study was designed to examine the role of Pacsin 2 in cardiac development and function. We investigated the development and electrophysiological properties of Pacsin 2 knockout (P2KO) hearts and single cardiomyocytes isolated from 11.5 and 15.5days old fetal mice. Immunofluorescence experiments confirmed the lack of Pacsin 2 protein expression in P2KO cardiac myocytes in comparison to wildtype (WT). Western blotting demonstrates low expression levels of connexin 43 and T-box 3 proteins in P2KO compared to wildtype (WT). Electrophysiology measurements including online Multi-Electrode Array (MEA) based field potential (FP) recordings on isolated whole heart of P2KO mice showed a prolonged AV-conduction time. Patch clamp measurements of P2KO cardiomyocytes revealed differences in action potential (AP) parameters and decreased pacemaker funny channel (I f ), as well as L-type Ca 2+ channel (I CaL ), and sodium channel (I Na ). These findings demonstrate that Pacsin 2 is necessary for cardiac development and function in mouse embryos, which will enhance our knowledge to better understand the genesis of cardiovascular diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regression analysis and transfer function in estimating the parameters of central pulse waves from brachial pulse wave.

PubMed

Chai Rui; Li Si-Man; Xu Li-Sheng; Yao Yang; Hao Li-Ling

2017-07-01

This study mainly analyzed the parameters such as ascending branch slope (A_slope), dicrotic notch height (Hn), diastolic area (Ad) and systolic area (As) diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), subendocardial viability ratio (SEVR), waveform parameter (k), stroke volume (SV), cardiac output (CO) and peripheral resistance (RS) of central pulse wave invasively and non-invasively measured. These parameters extracted from the central pulse wave invasively measured were compared with the parameters measured from the brachial pulse waves by a regression model and a transfer function model. The accuracy of the parameters which were estimated by the regression model and the transfer function model was compared too. Our findings showed that in addition to the k value, the above parameters of the central pulse wave and the brachial pulse wave invasively measured had positive correlation. Both the regression model parameters including A_slope, DBP, SEVR and the transfer function model parameters had good consistency with the parameters invasively measured, and they had the same effect of consistency. The regression equations of the three parameters were expressed by Y'=a+bx. The SBP, PP, SV, CO of central pulse wave could be calculated through the regression model, but their accuracies were worse than that of transfer function model.

Cardiac function adaptations in hibernating grizzly bears (Ursus arctos horribilis).

PubMed

Nelson, O Lynne; Robbins, Charles T

2010-03-01

Research on the cardiovascular physiology of hibernating mammals may provide insight into evolutionary adaptations; however, anesthesia used to handle wild animals may affect the cardiovascular parameters of interest. To overcome these potential biases, we investigated the functional cardiac phenotype of the hibernating grizzly bear (Ursus arctos horribilis) during the active, transitional and hibernating phases over a 4 year period in conscious rather than anesthetized bears. The bears were captive born and serially studied from the age of 5 months to 4 years. Heart rate was significantly different from active (82.6 +/- 7.7 beats/min) to hibernating states (17.8 +/- 2.8 beats/min). There was no difference from the active to the hibernating state in diastolic and stroke volume parameters or in left atrial area. Left ventricular volume:mass was significantly increased during hibernation indicating decreased ventricular mass. Ejection fraction of the left ventricle was not different between active and hibernating states. In contrast, total left atrial emptying fraction was significantly reduced during hibernation (17.8 +/- 2.8%) as compared to the active state (40.8 +/- 1.9%). Reduced atrial chamber function was also supported by reduced atrial contraction blood flow velocities and atrial contraction ejection fraction during hibernation; 7.1 +/- 2.8% as compared to 20.7 +/- 3% during the active state. Changes in the diastolic cardiac filling cycle, especially atrial chamber contribution to ventricular filling, appear to be the most prominent macroscopic functional change during hibernation. Thus, we propose that these changes in atrial chamber function constitute a major adaptation during hibernation which allows the myocardium to conserve energy, avoid chamber dilation and remain healthy during a period of extremely low heart rates. These findings will aid in rational approaches to identifying underlying molecular mechanisms.

Cellular apoptosis and cardiac dysfunction in STZ-induced diabetic rats attenuated by anthocyanins via activation of IGFI-R/PI3K/Akt survival signaling.

PubMed

Huang, Pei-Chen; Wang, Guei-Jane; Fan, Ming-Jen; Asokan Shibu, Marthandam; Liu, Yin-Tso; Padma Viswanadha, Vijaya; Lin, Yi-Lin; Lai, Chao-Hung; Chen, Yu-Feng; Liao, Hung-En; Huang, Chih-Yang

2017-12-01

Anthocyanins are known cyto-protective agents against various stress conditions. In this study cardio-protective effect of anthocyanins from black rice against diabetic mellitus (DM) was evaluated using a streptozotocin (STZ)-induced DM rat model. Five-week-old male Wistar rats were administered with STZ (55 mg kg -1 , IP) to induce DM; rats in the treatment group received 250 mg oral anthocyanin/kg/day during the 4-week treatment period. DM and the control rats received normal saline through oral gavage. The results reveal that STZ-induced DM elevates myocardial apoptosis and associated proapoptotic proteins but down-regulates the proteins of IGF1R mediated survival signaling mechanism. Furthermore, the functional parameters such as the ejection-fraction and fraction-shortening in the DM rat hearts declined considerably. However, the rats treated with anthocyanins significantly reduced apoptosis and the associated proapoptotic proteins and further increased the survival signals to restore the cardiac functions in DM rats. Anthocyanin supplementation enhances cardiomyocyte survival and restores cardiac function. © 2017 Wiley Periodicals, Inc.

Detection and monitoring of cardiotoxicity-what does modern cardiology offer?

PubMed

Jurcut, Ruxandra; Wildiers, Hans; Ganame, Javier; D'hooge, Jan; Paridaens, Robert; Voigt, Jens-Uwe

2008-05-01

With new anticancer therapies, many patients can have a long life expectancy. Treatment-related comorbidities become an issue for cancer survivors. Cardiac toxicity remains an important side effect of anticancer therapies. Myocardial dysfunction can become apparent early or long after end of therapy and may be irreversible. Detection of cardiac injury is crucial since it may facilitate early therapeutic measures. Traditionally, chemotherapy-induced cardiotoxicity has been detected by measuring changes in left ventricular ejection fraction. This parameter is, however, insensitive to subtle changes in myocardial function as they occur in early cardiotoxicity. This review will discuss conventional and modern cardiologic approaches of assessing myocardial function. It will focus on Doppler myocardial imaging, a method which allows to sensitively measure myocardial function parameters like myocardial velocity, deformation (strain), or deformation rate (strain rate) and which has been shown to reliably detect early abnormalities in both regional and global myocardial function in an early stage. Other newer echocardiographic function estimators are based on automated border detection algorithms and ultrasonic integrated backscatter analysis. A further technique to be discussed is dobutamine stress echocardiography. The use of new biomarkers like B-type natriuretic peptide and troponin and less often used imaging techniques like magnetic resonance imaging and computed tomography will also be mentioned.

Design of a cardiac monitor in terms of parameters of QRS complex.

PubMed

Chen, Zhen-cheng; Ni, Li-li; Su, Ke-ping; Wang, Hong-yan; Jiang, Da-zong

2002-08-01

Objective. To design a portable cardiac monitor system based on the available ordinary ECG machine and works on the basis of QRS parameters. Method. The 80196 single chip microcomputer was used as the central microprocessor and real time electrocardiac signal was collected and analyzed [correction of analysized] in the system. Result. Apart from the performance of an ordinary monitor, this machine possesses also the following functions: arrhythmia analysis, HRV analysis, alarm, freeze, and record of automatic papering. Convenient in carrying, the system is powered by AC or DC sources. Stability, low power and low cost are emphasized in the hardware design; and modularization method is applied in software design. Conclusion. Popular in usage and low cost made the portable monitor system suitable for use under simple conditions.

Dysregulated Arginine Metabolism and Cardiopulmonary Dysfunction in Patients with Thalassaemia

PubMed Central

Morris, Claudia R.; Kim, Hae-Young; Klings, Elizabeth S.; Wood, John; Porter, John B.; Trachtenberg, Felicia; Sweeters, Nancy; Olivieri, Nancy F; Kwiatkowski, Janet L; Virzi, Lisa; Hassell, Kathryn; Taher, Ali; Neufeld, Ellis J; Thompson, Alexis A.; Larkin, Sandra; Suh, Jung H.; Vichinsky, Elliott P; Kuypers, Frans A.

2015-01-01

Pulmonary hypertension (PH) commonly develops in thalassaemia syndromes, but is poorly characterized. The goal of this study was to provide a comprehensive description of the cardiopulmonary and biological profile of patients with thalassaemia at risk for PH. A case-control study of thalassaemia patients at high versus low PH-risk was performed. A single cross-sectional measurement for variables reflecting cardiopulmonary status and biological pathophysiology were obtained, including Doppler-echocardiography, 6-minute-walk-test, Borg Dyspnea Score, New York Heart Association functional class, cardiac magnetic resonance imaging (MRI), chest-computerized tomography, pulmonary function testing and laboratory analyses targeting mechanism of coagulation, inflammation, haemolysis, adhesion and the arginine-nitric oxide pathway. Twenty-seven thalassaemia patients were evaluated, 14 with an elevated tricuspid-regurgitant-jet-velocity (TRV) ≥2.5m/s. Patients with increased TRV had a higher frequency of splenectomy, and significantly larger right atrial size, left atrial volume and left septal-wall thickness on echocardiography and/or MRI, with elevated biomarkers of abnormal coagulation, lactate dehydrogenase levels and arginase concentration, and lower arginine-bioavailability compared to low-risk patients. Arginase concentration correlated significantly to several echocardiography/MRI parameters of cardiovascular function in addition to global-arginine-bioavailability and biomarkers of haemolytic rate, including lactate dehydrogenase, haemoglobin and bilirubin. Thalassaemia patients with a TRV ≥2.5m/s have additional echocardiography and cardiac-MRI parameters suggestive of right and left-sided cardiac dysfunction. In addition, low arginine bioavailability may contribute to cardiopulmonary dysfunction in β-thalassaemia. PMID:25907665

Changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy using UPLC/Q-TOF/MS analysis.

PubMed

Dong, Shifen; Zhang, Rong; Liang, Yaoyue; Shi, Jiachen; Li, Jiajia; Shang, Fei; Mao, Xuezhou; Sun, Jianning

2017-01-01

Diabetic cardiomyopathy (DCM) is a serious cardiac dysfunction induced by changes in the structure and contractility of the myocardium that are initiated in part by alterations in energy substrates. The underlying mechanisms of DCM are still under controversial. The observation of lipids, especially lipidomics profiling, can provide an insight into the know the biomarkers of DCM. The aim of our research was to detect changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy. Diabetic cardiomyopathy was induced by feeding a high-sucrose/fat diet (HSFD) for 28 weeks and streptozotocin (30 mg/kg, intraperitoneally). The ultra-high-performance liquid chromatography (UPLC) coupled to quadruple time-of flight (QTOF) mass spectrometer was used to acquire and analyze the lipidomics profiling of myocardial tissue. Meanwhile, parameters of cardiac function were collected using cardiac catheterization, and the cardiac index was calculated, and fasting blood glucose and lipid levels were measured by an ultraviolet spectrophotometric method. We detected 3023 positive ion peaks and 300 negative ion peaks. Levels of phosphatidylcholine (PC) (22:6/18:2), PC (22:6/18:1), PC (20:4/16:1), PC (16:1/18:3), phosphatidylethanolamine (PE) (20:4/18:2), and PE (20:4/16:0) were down-regulated, and PC (20:2/18:2), PC (18:0/16:0), and PC (20:4/18:0) were up-regulated in DCM model rats, when compared with control rats. Cardiac functions signed as values of left ventricular systolic pressure, maximal uprising velocity of left ventricular pressure and maximal decreasing velocity of left ventricular pressure were injured by 21-44%, and the cardiac index was increased by 25%, and fasting blood glucose and lipids were increased by 34-368%. Meanwhile, the cardiac lipid-related biomarkers have significant correlation with changes of cardiac function and cardiac index. UPLC/Q-TOF/MS analysis data suggested changes of some potential lipid biomarkers in the development of cardiac dysfunction and hypertrophy of diabetic cardiomyopathy, which may serve as potential important targets for clinical diagnosis and therapeutic intervention of DCM in the future.

IDENTIFICATION OF EMERGING SUB-POPULATIONS SUSCEPTIBLE TO ADVERSE HEALTH EFFECTS ASSOCIATED WITH AIR PARTICULATE EXPOSURE

EPA Science Inventory

The overall weight of evidence from panel, clinical, and toxicological studies has demonstrated the ability of ambient air particulate matter (PM) exposure to induce a variety of extra-pulmonary effects ranging from alterations in hematological parameters to cardiac function. Alt...

Percent Emphysema and Right Ventricular Structure and Function

PubMed Central

Grau, Maria; Lima, Joao A.; Hoffman, Eric A.; Bluemke, David A.; Carr, J. Jeffrey; Chahal, Harjit; Enright, Paul L; Jain, Aditya; Prince, Martin R.; Kawut, Steven M.

2013-01-01

Background: Severe COPD can lead to cor pulmonale and emphysema and is associated with impaired left ventricular (LV) filling. We evaluated whether emphysema and airflow obstruction would be associated with changes in right ventricular (RV) structure and function and whether these associations would differ by smoking status. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI on 5,098 participants without clinical cardiovascular disease aged 45 to 84 years. RV and emphysema measures were available for 4,188 participants. Percent emphysema was defined as the percentage of voxels below −910 Hounsfield units in the lung windows on cardiac CT scans. Generalized additive models were used to control for confounders and adjust for respective LV parameters. Results: Participants consisted of 13% current smokers, 36% former smokers, and 52% never smokers. Percent emphysema was inversely associated with RV end-diastolic volume, stroke volume, cardiac output, and mass prior to adjustment for LV measures. After adjustment for LV end-diastolic volume, greater percent emphysema was associated with greater RV end-diastolic volume (+1.5 mL, P = .03) among current smokers, smaller RV end-diastolic volume (−0.8 mL, P = .02) among former smokers, and similar changes among never smokers. Conclusions: Percent emphysema was associated with smaller RV volumes and lower mass. The relationship of emphysema to cardiac function is complex but likely involves increased pulmonary vascular resistance, predominantly with reduced cardiac output, pulmonary hyperinflation, and accelerated cardiopulmonary aging. PMID:23450302

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors.

PubMed

Anyfanti, Panagiota; Triantafyllou, Areti; Gkaliagkousi, Eugenia; Triantafyllou, Georgios; Koletsos, Nikolaos; Chatzimichailidou, Sophia; Panagopoulos, Panagiotis; Botis, Ioannis; Aslanidis, Spyros; Douma, Stella

2017-06-01

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima-media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.

Towards Personalized Cardiology: Multi-Scale Modeling of the Failing Heart

PubMed Central

Amr, Ali; Neumann, Dominik; Georgescu, Bogdan; Seegerer, Philipp; Kamen, Ali; Haas, Jan; Frese, Karen S.; Irawati, Maria; Wirsz, Emil; King, Vanessa; Buss, Sebastian; Mereles, Derliz; Zitron, Edgar; Keller, Andreas; Katus, Hugo A.; Comaniciu, Dorin; Meder, Benjamin

2015-01-01

Background Despite modern pharmacotherapy and advanced implantable cardiac devices, overall prognosis and quality of life of HF patients remain poor. This is in part due to insufficient patient stratification and lack of individualized therapy planning, resulting in less effective treatments and a significant number of non-responders. Methods and Results State-of-the-art clinical phenotyping was acquired, including magnetic resonance imaging (MRI) and biomarker assessment. An individualized, multi-scale model of heart function covering cardiac anatomy, electrophysiology, biomechanics and hemodynamics was estimated using a robust framework. The model was computed on n=46 HF patients, showing for the first time that advanced multi-scale models can be fitted consistently on large cohorts. Novel multi-scale parameters derived from the model of all cases were analyzed and compared against clinical parameters, cardiac imaging, lab tests and survival scores to evaluate the explicative power of the model and its potential for better patient stratification. Model validation was pursued by comparing clinical parameters that were not used in the fitting process against model parameters. Conclusion This paper illustrates how advanced multi-scale models can complement cardiovascular imaging and how they could be applied in patient care. Based on obtained results, it becomes conceivable that, after thorough validation, such heart failure models could be applied for patient management and therapy planning in the future, as we illustrate in one patient of our cohort who received CRT-D implantation. PMID:26230546

Structural and functional affection of the heart in protein energy malnutrition patients on admission and after nutritional recovery.

PubMed

El-Sayed, H L; Nassar, M F; Habib, N M; Elmasry, O A; Gomaa, S M

2006-04-01

The pathogenesis of different malnutrition diseases was suggested to affect the heart. This study was designed to detect cardiac affection in protein energy malnutrition (PEM) patients, whether clinically or by electrocardiogram (ECG) and echocardiogram, and to assess the value of the cardiac marker troponin I in patients at risk of myocardial injury with special emphasis on the effect of nutritional rehabilitation. The present study was carried out on 30 PEM infants (16 nonedematous - 14 edematous) and 10 apparently healthy age and sex-matched infants acting as the control group. All studied infants were subjected to full history taking laying stress on dietetic history, thorough clinical and anthropometric measurements. Echocardiography and ECG were also performed. Laboratory investigations were performed including complete blood count, CRP, total proteins, albumin, liver and kidney functions as well as estimation of troponin-I in blood by immulite. Following initial evaluation, all malnourished infants were subjected to nutritional rehabilitation program for approximately 8 weeks, after which the patients were re-evaluated using the same preinterventional parameters. The results of the present study demonstrated that electrical properties of myocardium assessed by ECG showed significant decrease of R wave and QTc interval in patients compared to controls with significant improvement after nutritional rehabilitation. Echocardigraphic changes showed that cardiac mass index was significantly lower in both groups of malnourished cases compared to the controls with significant increase after nutritional rehabilitation. The study showed that the parameters of left ventricular (LV) systolic function which are the ejection fraction, fractional shortening and velocity of circumferential fiber shortening were not significantly reduced in patients compared to the controls. The diastolic function also showed no significant difference in the E wave/A wave (e/a) ratio between patients and controls. However, the systolic time interval showed significantly higher LV pre-ejection index in patients in comparison to controls. Edematous and nonedematous cases did not show any significant differences in ECG and echocardigraphic data before or after nutritional rehabilitation. The hearts of two severely affected patients uniquely demonstrated marked decrease of LV end diastolic diameter (LEVDd) together with the detection of troponin-I in their sera. We can conclude that malnutrition, regardless of its type, has a definite effect on cardiac volume, muscle mass, as well as the electrical properties of the myocardium. The systolic functions of the heart are affected more than the diastolic functions and this affection becomes manifest only in severe cases and may constitute a bad prognostic parameter thus necessitating more intense management and strict follow-up of such cases.

Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.

PubMed

Kim, S Y; Montoya, A; Zbilut, J P; Mawulawde, K; Sullivan, H J; Lonchyna, V A; Terrell, M R; Pifarré, R

1996-02-01

Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.

Sex-based differences in plasma chemistry and cardiac marker test results in Siamese fighting fowl.

PubMed

Sribhen, Choosri; Choothesa, Apassara; Songserm, Thaveesak; Issariyodom, Supaporn; Sribhen, Kosit

2006-09-01

Variations in the results of plasma chemistry analysis as a function of sex have rarely been demonstrated in avian species. The aim of the present study was to investigate sex-related differences in values for routine biochemical variables, including conventional muscle enzymes, and novel cardiac markers in female and male Siamese fighting fowl. Plasma chemistry analytes and cardiac marker proteins (creatine kinase-MB and cardiac troponin T) were measured in 70 Siamese fighting fowl using automated chemistry and immunoassay analyzers. Data were compared by 2-tailed t tests between sexes, and Spearman rank correlation between conventional and novel cardiac markers. Male fowl had significantly higher uric acid concentration and gamma-glutamyltransferase activity; whereas, female fowl had significantly higher total cholesterol, triglycerides, and calcium concentrations, and alkaline phosphatase activity. As compared with female fowl, the fighting cocks also had significantly higher plasma concentrations of creatine kinase-MB and cardiac troponin T. Significant correlations between cardiac troponin T, but not creatine kinase-MB, and the activities of conventional muscle enzymes (creatine kinase, aspartate aminotransferase and lactate dehydrogenase) were observed in male but not in female fowl. These results indicate that sex-specific differences exist for several biochemical parameters and cardiac marker proteins in fighting fowl, and that such differences should be considered in interpreting laboratory test results.

Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury.

PubMed

Candela-Toha, Ángel; Pardo, María Carmen; Pérez, Teresa; Muriel, Alfonso; Zamora, Javier

2018-04-20

and objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Using a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. AKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. Postoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

The relationship between physical performance and cardiac function in an elderly Russian cohort.

PubMed

Tadjibaev, Pulod; Frolova, Elena; Gurina, Natalia; Degryse, Jan; Vaes, Bert

2014-01-01

This study aims to determine the cardiac dysfunction prevalence, to investigate the relationship between the Short Physical Performance Battery (SPPB) test and structural and functional echocardiographic parameters and to determine whether SPPB scores and cardiac dysfunction are independent mortality predictors in an elderly Russian population. A random sample of 284 community-dwelling adults aged 65 and older were selected from a population-based register and divided into two age groups (65-74 and ≥75). The SPPB test, echocardiography and all-cause mortality were measured. The prevalence of cardiac dysfunction was 12% in the 65-74 group and 23% in the ≥75 group. The multivariate models could explain 15% and 23% of the SPPB score total variance for the 65-74 and ≥75 age groups, respectively. In the younger age group, the mean follow-up time was 2.6±0.46 years, and the adjusted hazard ratio (HR) for risk of mortality from cardiac dysfunction was 4.9. In the older age group, the mean follow-up time was 2.4±0.61 years, and both cardiac dysfunction and poor physical performance were found to be independent predictors of mortality (adjusted HR=3.4 and adjusted HR=4.2, respectively). The cardiac dysfunction prevalence in this elderly Russian population was found to be comparable to, or even lower than, reported prevalences for Western countries. Furthermore, the observed correlations between echocardiographic abnormalities and SPPB scores were limited. Cardiac dysfunction was shown to be a strong mortality predictor in both age groups, and poor physical performance was identified as an independent mortality predictor in the oldest subjects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chronic Cardiac-Targeted RNA Interference for the Treatment of Heart Failure Restores Cardiac Function and Reduces Pathological Hypertrophy

PubMed Central

Suckau, Lennart; Fechner, Henry; Chemaly, Elie; Krohn, Stefanie; Hadri, Lahouaria; Kockskämper, Jens; Westermann, Dirk; Bisping, Egbert; Ly, Hung; Wang, Xiaomin; Kawase, Yoshiaki; Chen, Jiqiu; Liang, Lifan; Sipo, Isaac; Vetter, Roland; Weger, Stefan; Kurreck, Jens; Erdmann, Volker; Tschope, Carsten; Pieske, Burkert; Lebeche, Djamel; Schultheiss, Heinz-Peter; Hajjar, Roger J.; Poller, Wolfgang Ch.

2009-01-01

Background RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. We report on targeted RNAi for the treatment of heart failure (HF), an important disorder in humans resulting from multiple etiologies. Successful treatment of HF is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban (PLB), a key regulator of cardiac Ca2+ homeostasis. Whereas gene therapy rests on recombinant protein expression as its basic principle, RNAi therapy employs regulatory RNAs to achieve its effect. Methods and Results We describe structural requirements to obtain high RNAi activity from adenoviral (AdV) and adeno-associated virus (AAV9) vectors and show that an AdV short hairpin RNA vector (AdV-shRNA) silenced PLB in cardiomyocytes (NRCMs) and improved hemodynamics in HF rats 1 month after aortic root injection. For simplified long-term therapy we developed a dimeric cardiotropic AAV vector (rAAV9-shPLB) delivering RNAi activity to the heart via intravenous injection. Cardiac PLB protein was reduced to 25% and SERCA2a suppression in the HF groups was rescued. In contrast to traditional vectors rAAV9 shows high affinity for myocardium, but low affinity for liver and other organs. rAAV9-shPLB therapy restored diastolic (LVEDP, dp/dtmin, Tau) and systolic (fractional shortening) functional parameters to normal range. The massive cardiac dilation was normalized and the cardiac hypertrophy, cardiomyocyte diameter and cardiac fibrosis significantly reduced. Importantly, there was no evidence of microRNA deregulation or hepatotoxicity during these RNAi therapies. Conclusion Our data show, for the first time, high efficacy of an RNAi therapeutic strategy in a cardiac disease. PMID:19237664

Design of a short nonuniform acquisition protocol for quantitative analysis in dynamic cardiac SPECT imaging - a retrospective 123 I-MIBG animal study.

PubMed

Zan, Yunlong; Long, Yong; Chen, Kewei; Li, Biao; Huang, Qiu; Gullberg, Grant T

2017-07-01

Our previous works have found that quantitative analysis of 123 I-MIBG kinetics in the rat heart with dynamic single-photon emission computed tomography (SPECT) offers the potential to quantify the innervation integrity at an early stage of left ventricular hypertrophy. However, conventional protocols involving a long acquisition time for dynamic imaging reduce the animal survival rate and thus make longitudinal analysis difficult. The goal of this work was to develop a procedure to reduce the total acquisition time by selecting nonuniform acquisition times for projection views while maintaining the accuracy and precision of estimated physiologic parameters. Taking dynamic cardiac imaging with 123 I-MIBG in rats as an example, we generated time activity curves (TACs) of regions of interest (ROIs) as ground truths based on a direct four-dimensional reconstruction of experimental data acquired from a rotating SPECT camera, where TACs represented as the coefficients of B-spline basis functions were used to estimate compartmental model parameters. By iteratively adjusting the knots (i.e., control points) of B-spline basis functions, new TACs were created according to two rules: accuracy and precision. The accuracy criterion allocates the knots to achieve low relative entropy between the estimated left ventricular blood pool TAC and its ground truth so that the estimated input function approximates its real value and thus the procedure yields an accurate estimate of model parameters. The precision criterion, via the D-optimal method, forces the estimated parameters to be as precise as possible, with minimum variances. Based on the final knots obtained, a new protocol of 30 min was built with a shorter acquisition time that maintained a 5% error in estimating rate constants of the compartment model. This was evaluated through digital simulations. The simulation results showed that our method was able to reduce the acquisition time from 100 to 30 min for the cardiac study of rats with 123 I-MIBG. Compared to a uniform interval dynamic SPECT protocol (1 s acquisition interval, 30 min acquisition time), the newly proposed protocol with nonuniform interval achieved comparable (K1 and k2, P = 0.5745 for K1 and P = 0.0604 for k2) or better (Distribution Volume, DV, P = 0.0004) performance for parameter estimates with less storage and shorter computational time. In this study, a procedure was devised to shorten the acquisition time while maintaining the accuracy and precision of estimated physiologic parameters in dynamic SPECT imaging. The procedure was designed for 123 I-MIBG cardiac imaging in rat studies; however, it has the potential to be extended to other applications, including patient studies involving the acquisition of dynamic SPECT data. © 2017 American Association of Physicists in Medicine.

The Cardiac Atlas Project--an imaging database for computational modeling and statistical atlases of the heart.

PubMed

Fonseca, Carissa G; Backhaus, Michael; Bluemke, David A; Britten, Randall D; Chung, Jae Do; Cowan, Brett R; Dinov, Ivo D; Finn, J Paul; Hunter, Peter J; Kadish, Alan H; Lee, Daniel C; Lima, Joao A C; Medrano-Gracia, Pau; Shivkumar, Kalyanam; Suinesiaputra, Avan; Tao, Wenchao; Young, Alistair A

2011-08-15

Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape and wall motion and characterize cardiac function among and within population groups. Three main open-source software components were developed: (i) a database with web-interface; (ii) a modeling client for 3D + time visualization and parametric description of shape and motion; and (iii) open data formats for semantic characterization of models and annotations. The database was implemented using a three-tier architecture utilizing MySQL, JBoss and Dcm4chee, in compliance with the DICOM standard to provide compatibility with existing clinical networks and devices. Parts of Dcm4chee were extended to access image specific attributes as search parameters. To date, approximately 3000 de-identified cardiac imaging examinations are available in the database. All software components developed by the CAP are open source and are freely available under the Mozilla Public License Version 1.1 (http://www.mozilla.org/MPL/MPL-1.1.txt). http://www.cardiacatlas.org a.young@auckland.ac.nz Supplementary data are available at Bioinformatics online.

Cardiac-specific suppression of NF-κB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system.

PubMed

Thomas, Candice M; Yong, Qian Chen; Rosa, Rodolfo M; Seqqat, Rachid; Gopal, Shanthi; Casarini, Dulce E; Jones, W Keith; Gupta, Sudhiranjan; Baker, Kenneth M; Kumar, Rajesh

2014-10-01

Activation of NF-κB signaling in the heart may be protective or deleterious depending on the pathological context. In diabetes, the role of NF-κB in cardiac dysfunction has been investigated using pharmacological approaches that have a limitation of being nonspecific. Furthermore, the specific cellular pathways by which NF-κB modulates heart function in diabetes have not been identified. To address these questions, we used a transgenic mouse line expressing mutated IκB-α in the heart (3M mice), which prevented activation of canonical NF-κB signaling. Diabetes was developed by streptozotocin injections in wild-type (WT) and 3M mice. Diabetic WT mice developed systolic and diastolic cardiac dysfunction by the 12th week, as measured by echocardiography. In contrast, cardiac function was preserved in 3M mice up to 24 wk of diabetes. Diabetes induced an elevation in cardiac oxidative stress in diabetic WT mice but not 3M mice compared with nondiabetic control mice. In diabetic WT mice, an increase in the phospholamban/sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 ratio and decrease in ryanodine receptor expression were observed, whereas diabetic 3M mice showed an opposite effect on these parameters of Ca(2+) handling. Significantly, renin-angiotensin system activity was suppressed in diabetic 3M mice compared with an increase in WT animals. In conclusion, these results demonstrate that inhibition of NF-κB signaling in the heart prevents diabetes-induced cardiac dysfunction through preserved Ca(2+) handling and inhibition of the cardiac renin-angiotensin system.

Cardiac-specific suppression of NF-κB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system

PubMed Central

Thomas, Candice M.; Yong, Qian Chen; Rosa, Rodolfo M.; Seqqat, Rachid; Gopal, Shanthi; Casarini, Dulce E.; Jones, W. Keith; Gupta, Sudhiranjan; Baker, Kenneth M.

2014-01-01

Activation of NF-κB signaling in the heart may be protective or deleterious depending on the pathological context. In diabetes, the role of NF-κB in cardiac dysfunction has been investigated using pharmacological approaches that have a limitation of being nonspecific. Furthermore, the specific cellular pathways by which NF-κB modulates heart function in diabetes have not been identified. To address these questions, we used a transgenic mouse line expressing mutated IκB-α in the heart (3M mice), which prevented activation of canonical NF-κB signaling. Diabetes was developed by streptozotocin injections in wild-type (WT) and 3M mice. Diabetic WT mice developed systolic and diastolic cardiac dysfunction by the 12th week, as measured by echocardiography. In contrast, cardiac function was preserved in 3M mice up to 24 wk of diabetes. Diabetes induced an elevation in cardiac oxidative stress in diabetic WT mice but not 3M mice compared with nondiabetic control mice. In diabetic WT mice, an increase in the phospholamban/sarco(endo)plasmic reticulum Ca2+-ATPase 2 ratio and decrease in ryanodine receptor expression were observed, whereas diabetic 3M mice showed an opposite effect on these parameters of Ca2+ handling. Significantly, renin-angiotensin system activity was suppressed in diabetic 3M mice compared with an increase in WT animals. In conclusion, these results demonstrate that inhibition of NF-κB signaling in the heart prevents diabetes-induced cardiac dysfunction through preserved Ca2+ handling and inhibition of the cardiac renin-angiotensin system. PMID:25085967

Pulse wave velocity and cardiac autonomic function in type 2 diabetes mellitus.

PubMed

Chorepsima, Stamatina; Eleftheriadou, Ioanna; Tentolouris, Anastasios; Moyssakis, Ioannis; Protogerou, Athanasios; Kokkinos, Alexandros; Sfikakis, Petros P; Tentolouris, Nikolaos

2017-05-19

Increased carotid-femoral pulse wave velocity (PWV) has been associated with incident cardiovascular disease, independently of traditional risk factors. Cardiac autonomic dysfunction is a common complication of diabetes and has been associated with reduced aortic distensibility. However, the association of cardiac autonomic dysfunction with PWV is not known. In this study we examined the association between cardiac autonomic function and PWV in subjects with type 2 diabetes mellitus. A total of 290 patients with type 2 diabetes were examined. PWV was measured at the carotid-femoral segment with applanation tonometry. Central mean arterial blood pressure (MBP) was determined by the same apparatus. Participants were classified as having normal (n = 193) or abnormal (n = 97) PWV values using age-corrected values. Cardiac autonomic nervous system activity was determined by measurement of parameters of heart rate variability (HRV). Subjects with abnormal PWV were older, had higher arterial blood pressure and higher heart rate than those with normal PWV. Most of the values of HRV were significantly lower in subjects with abnormal than in those with normal PWV. Multivariate analysis, after controlling for various confounding factors, demonstrated that abnormal PWV was associated independently only with peripheral MBP [odds ratio (OR) 1.049, 95% confidence intervals (CI) 1.015-1.085, P = 0.005], central MBP (OR 1.052, 95% CI 1.016-1.088, P = 0.004), log total power (OR 0.490, 95% CI 0.258-0.932, P = 0.030) and log high frequency power (OR 0.546, 95% CI 0.301-0.991, P = 0.047). In subjects with type 2 diabetes, arterial blood pressure and impaired cardiac autonomic function is associated independently with abnormal PWV.

The emerging phenotype of long-term survivors with infantile Pompe disease

PubMed Central

Prater, Sean N.; Banugaria, Suhrad G.; DeArmey, Stephanie M.; Botha, Eleanor G.; Stege, Erin M.; Case, Laura E.; Jones, Harrison N.; Phornphutkul, Chanika; Wang, Raymond Y.; Young, Sarah P.; Kishnani, Priya S.

2013-01-01

Purpose Enzyme replacement therapy with alglucosidase alfa for infantile Pompe disease has improved survival creating new management challenges. We describe an emerging phenotype in a retrospective review of long-term survivors. Methods Inclusion criteria included ventilator-free status and age ≤6 months at treatment initiation, and survival to age ≥5 years. Clinical outcome measures included invasive ventilator-free survival and parameters for cardiac, pulmonary, musculoskeletal, gross motor and ambulatory status; growth; speech, hearing, and swallowing; and gastrointestinal and nutritional status. Results Eleven of 17 patients met study criteria. All were cross-reactive immunologic material-positive, alive, and invasive ventilator-free at most recent assessment, with a median age of 8.0 years (range: 5.4 to 12.0 years). All had marked improvements in cardiac parameters. Commonly present were gross motor weakness, motor speech deficits, sensorineural and/or conductive hearing loss, osteopenia, gastroesophageal reflux disease, and dysphagia with aspiration risk. Seven of 11 patients were independently ambulatory and four required the use of assistive ambulatory devices. All long-term survivors had low or undetectable anti-alglucosidase alfa antibody titers. Conclusions Long-term survivors exhibited sustained improvements in cardiac parameters and gross motor function. Residual muscle weakness, hearing loss, risk for arrhythmias, hypernasal speech, dysphagia with risk for aspiration, and osteopenia were commonly observed findings. PMID:22538254

Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction.

PubMed

Wang, Jiaxing; Lu, Songhe; Zheng, Qijun; Hu, Nan; Yu, Wenjun; Li, Na; Liu, Min; Gao, Beilei; Zhang, Guoyong; Zhang, Yingmei; Wang, Haichang

2016-07-01

Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteins for biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage.

Accelerating cine-MR Imaging in Mouse Hearts Using Compressed Sensing

PubMed Central

Wech, Tobias; Lemke, Angela; Medway, Debra; Stork, Lee-Anne; Lygate, Craig A; Neubauer, Stefan; Köstler, Herbert; Schneider, Jürgen E

2011-01-01

Purpose To combine global cardiac function imaging with compressed sensing (CS) in order to reduce scan time and to validate this technique in normal mouse hearts and in a murine model of chronic myocardial infarction. Materials and Methods To determine the maximally achievable acceleration factor, fully acquired cine data, obtained in sham and chronically infarcted (MI) mouse hearts were 2–4-fold undersampled retrospectively, followed by CS reconstruction and blinded image segmentation. Subsequently, dedicated CS sampling schemes were implemented at a preclinical 9.4 T magnetic resonance imaging (MRI) system, and 2- and 3-fold undersampled cine data were acquired in normal mouse hearts with high temporal and spatial resolution. Results The retrospective analysis demonstrated that an undersampling factor of three is feasible without impairing accuracy of cardiac functional parameters. Dedicated CS sampling schemes applied prospectively to normal mouse hearts yielded comparable left-ventricular functional parameters, and intra- and interobserver variability between fully and 3-fold undersampled data. Conclusion This study introduces and validates an alternative means to speed up experimental cine-MRI without the need for expensive hardware. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc. PMID:21932360

Cilostazol protects mice against myocardium ischemic/reperfusion injury by activating a PPARγ/JAK2/STAT3 pathway.

PubMed

Li, Jiangjin; Xiang, Xiaoli; Gong, Xiaoxuan; Shi, Yafei; Yang, Jing; Xu, Zuo

2017-10-01

Myocardial ischemia/reperfusion (MIR) injury causes severe arrhythmias and a high lethality. The present study is designed to investigate the effect of cilostazol on MIR injury and the underlying mechaism. We measured the effects of cilostazol on heart function parameters in a mouse model of MIR. Proinflammatory cytokines and apoptosis proteins in the myocardium were examined to investigate the anti-inflammatory and anti-apoptosis ability of cilostazol. The participation of PPARγ/JAK2/STAT3 pathway was investigated. Results showed that the impairment of hemodynamic parameters caused by MIR was attenuated by cilostazol. The IL-6, IL-1β and TNF-a levels were all decreased by cilostazol. Cilostazol also significantly inhibited Bax and cleaved caspase-3 levels and restored the Bcl-2 levels. PPARγ, JAK2 and STAT3 were all activated by cilostazol. Treatment of inhibitors of them abolished the protective effects of cilostazol on cardiac function, myocardial inflammation and apoptosis. In summary, cilostazol alleviated the cardiac function impairment, myocardial inflammation and apoptosis induced by MIR. The results present a novel signaling mechanism that cilostazol protects MIR injury by activating a PPARγ/JAK2/STAT3 pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function

PubMed Central

Milner, Derek J.; Mavroidis, Manolis; Weisleder, Noah; Capetanaki, Yassemi

2000-01-01

Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (K m) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant role in mitochondrial positioning and respiratory function in cardiac and skeletal muscle. PMID:10995435

A statistical note on the redundancy of nine standard baroreflex parameters

NASA Technical Reports Server (NTRS)

Ludwig, David A.; Convertino, Victor A.

1991-01-01

An accepted method for measuring the responsiveness of the carotid-cardiac baroreflex to arterial pressure changes is to artificially stimulate the baroreceptors in the neck with a pressurized neck chamber. Nine physiological responses to this type of stimulation are quantified and used as indicators of the baroreflex response function. Thirty male humans between the ages of 27 and 46 underwent the carotid-cardiac baroreflex test. The data for the nine response parameters were analyzed by principle component factor analysis. The results indicated that 92.5 percent of the total variance across all nine parameters could be explained in four dimensions. The first two dimensions reflected location points for R-R interval and carotid distending pressure, respectively. The third factor was composed of measures reflecting the gain (responsiveness) of the reflex. The fourth dimension was the ratio of baseline R-R interval to the maximal R-R interval response during simulated hypertension. The data suggest that the analysis of all nine baroreflex parameters is likely to be redundant and researchers should account for these redundancies either in their analyses or conclusions.

Cardiovascular Adaptations to Long Duration Head-Down Tilt Bed Rest

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Martin, David S.; Perez, Sondar A.; Ribeiro, Christine; Stenger, Michael B.; Summers, Richard; Meck, Janice V.

2008-01-01

INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 days of bed rest, and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 minutes or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49. Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Intimal-medial thickness markedly decreased at bed rest days 21, 35 and 49. Several cardiac functional parameters including isovolumic relaxation time, ejection time and myocardial performance index were significantly increased (indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 days of bed rest. DISCUSSION: These data suggest that 6 head-down tilt bed rest alters cardiovascular structure and function in a pattern similar to short duration spaceflight. Additionally, the vascular alterations are primarily seen in the lower body, while vessels of the upper body are unaffected. KEY WORDS: spaceflight, orthostatic intolerance, hypotension, fluid-shift, plasma volume

Temporal patterns of cardiac performance and genes encoding heat shock proteins and metabolic sensors of an intertidal limpet Cellana toreuma during sublethal heat stress.

PubMed

Zhang, Shu; Han, Guo-dong; Dong, Yun-wei

2014-04-01

Intertidal invertebrates develop effective physiological adaptations to cope with the rapidly changing thermal environment in the intertidal zone. In the present study, the temporal patterns of heart rate, protein carbonyl groups, and genes encoding heat shock proteins (hsp70 and hsp90) and metabolic sensors (ampkα, ampkβ and sirt1) were measured to study the effect of sublethal heat stress on the cardiac function, oxidative stress, heat shock response and cellular metabolism of an intertidal limpet Cellana toreuma. All the physiological parameters are sensitive to temperature and duration of heat stress. Spearman correlation analysis revealed that the correlations between heart rate and levels of heat shock proteins mRNA and metabolic sensors mRNA were statistically significant. These results further suggest that cardiac function plays crucial roles in cellular energy metabolism and heat shock responses. The significant increase of protein carbonyl groups at 34°C after 4h exposure indicated that the failure of cardiac function and the increase of anaerobic metabolism partly leads to the increase of protein carbonyl groups. Generally, the physiological responses to heat stress are sensitive to temperature and are energy-consumptive, as indicated by the upregulation of metabolic sensors mRNA. However, the upregulation of heat shock proteins and metabolic sensors at the post-transcriptional level and related functions need to be confirmed in further experiments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Large-Animal Biventricular Working Heart Perfusion System with Low Priming Volume-Comparison between in vivo and ex vivo Cardiac Function.

PubMed

Abicht, Jan-Michael; Mayr, Tanja Axinja Jelena; Jauch, Judith; Guethoff, Sonja; Buchholz, Stefan; Reichart, Bruno; Bauer, Andreas

2018-01-01

Existing large-animal, ex vivo, cardiac perfusion models are restricted in their ability to establish an ischemia/reperfusion condition as seen in cardiac surgery or transplantation. Other working heart systems only challenge one ventricle or require a substantially larger priming volume. We describe a novel biventricular cardiac perfusion system with reduced priming volume. Juvenile pig hearts were cardiopleged, explanted, and reperfused ex vivo after 150 minutes of cold ischemia. Autologous whole blood was used as perfusate (minimal priming volume 350 mL). After 15 minutes of Langendorff perfusion (LM), the system was switched into a biventricular working mode (WM) and studied for 3 hours. During reperfusion, complete unloading of both ventricles and constant-pressure coronary perfusion was achieved. During working mode perfusion, the preload and afterload pressure of both ventricles was controlled within the targeted physiologic range. Functional parameters such as left ventricular work index were reduced in ex vivo working mode (in vivo: 787 ± 186 vs. 1 h WM 498 ± 66 mm Hg·mL/g·min; p  < 0.01), but remained stable throughout the following study period (3 h WM 517 ± 103 mm Hg·mL/g·min; p  = 0.63). Along with the elevated workload during WM, myocardial metabolism and oxygen consumption increased compared with LM (0.021 ± 0.08 vs. 0.06 ± 0.01 mL/min/g; 1 h after reperfusion). Histologic examination of the myocardium revealed no structural damage. In the ex vivo perfusion system, stable hemodynamic and metabolic conditions can be established for a period of 3 hours while functional and blood parameters are easily accessible. Moreover, because of the minimal priming volume, the novel ex vivo cardiac perfusion circuit allows for autologous perfusion, using the limited amount of blood available from the organ donating animal. Georg Thieme Verlag KG Stuttgart · New York.

Randomised controlled trial examining the effect of an outpatient exercise training programme on haemodynamics and cardiac MR parameters of right ventricular function in patients with pulmonary arterial hypertension: the ExPAH study protocol.

PubMed

Chia, Karen S W; Faux, Steven G; Wong, Peter K K; Holloway, Cameron; Assareh, Hassan; McLachlan, Craig S; Kotlyar, Eugene

2017-02-06

Pulmonary hypertension (PH) is a potentially life-threatening condition characterised by elevated pulmonary artery pressure. Early stage PH patients are often asymptomatic. Disease progression is associated with impairment of right ventricular function and progressive dyspnoea. Current guidelines recommend exercise training (grade IIa, level B). However, many questions remain regarding the mechanisms of improvement, intensity of supervision and optimal frequency, duration and intensity of exercise. This study will assess the effect of an outpatient rehabilitation programme on haemodynamics and cardiac right ventricular function in patients with pulmonary arterial hypertension (PAH), a subgroup of PH. This randomised controlled trial involves both a major urban tertiary and smaller regional hospital in New South Wales, Australia. The intervention will compare an outpatient rehabilitation programme with a control group (home exercise programme). Participants will be stable on oral PAH-specific therapy. The primary outcome measure will be right ventricular ejection fraction measured by cardiac MRI. Secondary outcomes will include haemodynamics measured by right heart catheterisation, endurance, functional capacity, health-related quality of life questionnaires and biomarkers of cardiac function and inflammation. Ethical approval has been granted by St Vincent's Hospital, Sydney (HREC/14/SVH/341). Results of this study will be disseminated through presentation at scientific conferences and in scientific journals. ACTRN12615001041549; pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cardiac structure and function predicts functional decline in the oldest old.

PubMed

Leibowitz, David; Jacobs, Jeremy M; Lande-Stessman, Irit; Gilon, Dan; Stessman, Jochanan

2018-02-01

Background This study examined the association between cardiac structure and function and the deterioration in activities of daily living (ADLs) in an age-homogenous, community-dwelling population of patients born in 1920-1921 over a five-year follow-up period. Design Longitudinal cohort study. Methods Patients were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920-1921. Patients underwent home echocardiography and were followed up for five years. Dependence was defined as needing assistance with one or more basic ADL. Standard echocardiographic assessment of cardiac structure and function, including systolic and diastolic function, was performed. Reassessment of ADLs was performed at the five-year follow-up. Results A total of 459 patients were included in the study. Of these, 362 (79%) showed a deterioration in at least one ADL at follow-up. Patients with functional deterioration had a significantly higher left ventricular mass index and left atrial volume with a lower ejection fraction. There was no significant difference between the diastolic parameters the groups in examined. When the data were examined categorically, a significantly larger percentage of patients with functional decline had an abnormal left ventricular ejection fraction and left ventricular hypertrophy. The association between left ventricular mass index and functional decline remained significant in all multivariate models. Conclusions In this cohort of the oldest old, an elevated left ventricular mass index, higher left atrial volumes and systolic, but not diastolic dysfunction, were predictive of functional disability.

Subclinical Disease Burden as Assessed by Whole-Body MRI in Subjects With Prediabetes, Subjects With Diabetes, and Normal Control Subjects From the General Population: The KORA-MRI Study.

PubMed

Bamberg, Fabian; Hetterich, Holger; Rospleszcz, Susanne; Lorbeer, Roberto; Auweter, Sigrid D; Schlett, Christopher L; Schafnitzel, Anina; Bayerl, Christian; Schindler, Andreas; Saam, Tobias; Müller-Peltzer, Katharina; Sommer, Wieland; Zitzelsberger, Tanja; Machann, Jürgen; Ingrisch, Michael; Selder, Sonja; Rathmann, Wolfgang; Heier, Margit; Linkohr, Birgit; Meisinger, Christa; Weber, Christian; Ertl-Wagner, Birgit; Massberg, Steffen; Reiser, Maximilian F; Peters, Annette

2017-01-01

Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, coronary artery disease, or peripheral artery disease were enrolled in a case-control study nested within the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and underwent comprehensive MRI assessment to characterize cerebral parameters (white matter lesions, microbleeds), cardiovascular parameters (carotid plaque, left ventricular function, and myocardial late gadolinium enhancement [LGE]), and metabolic parameters (hepatic proton-density fat fraction [PDFF] and subcutaneous and visceral abdominal fat). Among 400 subjects who underwent MRI, 103 subjects had prediabetes and 54 had established diabetes. Subjects with prediabetes had an increased risk for carotid plaque and adverse functional cardiac parameters, including reduced early diastolic filling rates as well as a higher prevalence of LGE compared with healthy control subjects. In addition, people with prediabetes had significantly elevated levels of PDFF and total and visceral fat. Thus, subjects with prediabetes show early signs of subclinical disease that include vascular, cardiac, and metabolic changes, as measured by whole-body MRI after adjusting for cardiometabolic risk factors. © 2017 by the American Diabetes Association.

Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents

PubMed Central

Hou, Jennifer H.; Kralj, Joel M.; Douglass, Adam D.; Engert, Florian; Cohen, Adam E.

2014-01-01

The cardiac action potential (AP) and the consequent cytosolic Ca2+ transient are key indicators of cardiac function. Natural developmental processes, as well as many drugs and pathologies change the waveform, propagation, or variability (between cells or over time) of these parameters. Here we apply a genetically encoded dual-function calcium and voltage reporter (CaViar) to study the development of the zebrafish heart in vivo between 1.5 and 4 days post fertilization (dpf). We developed a high-sensitivity spinning disk confocal microscope and associated software for simultaneous three-dimensional optical mapping of voltage and calcium. We produced a transgenic zebrafish line expressing CaViar under control of the heart-specific cmlc2 promoter, and applied ion channel blockers at a series of developmental stages to map the maturation of the action potential in vivo. Early in development, the AP initiated via a calcium current through L-type calcium channels. Between 90 and 102 h post fertilization (hpf), the ventricular AP switched to a sodium-driven upswing, while the atrial AP remained calcium driven. In the adult zebrafish heart, a sodium current drives the AP in both the atrium and ventricle. Simultaneous voltage and calcium imaging with genetically encoded reporters provides a new approach for monitoring cardiac development, and the effects of drugs on cardiac function. PMID:25309445

Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents.

PubMed

Hou, Jennifer H; Kralj, Joel M; Douglass, Adam D; Engert, Florian; Cohen, Adam E

2014-01-01

The cardiac action potential (AP) and the consequent cytosolic Ca(2+) transient are key indicators of cardiac function. Natural developmental processes, as well as many drugs and pathologies change the waveform, propagation, or variability (between cells or over time) of these parameters. Here we apply a genetically encoded dual-function calcium and voltage reporter (CaViar) to study the development of the zebrafish heart in vivo between 1.5 and 4 days post fertilization (dpf). We developed a high-sensitivity spinning disk confocal microscope and associated software for simultaneous three-dimensional optical mapping of voltage and calcium. We produced a transgenic zebrafish line expressing CaViar under control of the heart-specific cmlc2 promoter, and applied ion channel blockers at a series of developmental stages to map the maturation of the action potential in vivo. Early in development, the AP initiated via a calcium current through L-type calcium channels. Between 90 and 102 h post fertilization (hpf), the ventricular AP switched to a sodium-driven upswing, while the atrial AP remained calcium driven. In the adult zebrafish heart, a sodium current drives the AP in both the atrium and ventricle. Simultaneous voltage and calcium imaging with genetically encoded reporters provides a new approach for monitoring cardiac development, and the effects of drugs on cardiac function.

Influencing factors of NT-proBNP level inheart failure patients with different cardiacfunctions and correlation with prognosis.

PubMed

Xu, Liang; Chen, Yanchun; Ji, Yanni; Yang, Song

2018-06-01

Factors influencing N-terminal pro-brain natriuretic peptide (NT-proBNP) level in heart failure patients with different cardiac functions were identified to explore the correlations with prognosis. Eighty heart failure patients with different cardiac functions treated in Yixing People's Hospital from January 2016 to June 2017 were selected, and divided into two groups (group with cardiac function in class II and below and group with cardiac function in class III and above), according to the cardiac function classification established by New York Heart Association (NYHA). Blood biochemical test and outcome analysis were conducted to measure serum NT-proBNP and matrix metalloproteinase-9 (MMP-9) levels in patients with different cardiac functions, and correlations between levels of NT-proBNP and MMP-9 and left ventricular ejection fraction (LVEF) level were analyzed in patients with different cardiac functions at the same time. In addition, risk factors for heart failure in patients with different cardiac functions were analyzed. Compared with the group with cardiac function in class III and above, the group with cardiac function in class II and below had significantly lower serum NT-proBNP and MMP-9 levels (p<0.05). For echocardiogram indexes, left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) in the group with cardiac function in class II and below were obviously lower than those in the group with cardiac function in class III and above (p<0.05), while LVEF was higher in group with cardiac function in class II and below than that in group with cardiac function in class III and above (p<0.05). NT-proBNP and MMP-9 levels were negatively correlated with LVEF level [r=-0.8517 and -0.8517, respectively, p<0.001 (<0.05)]. Cardiac function in class III and above, increased NT-proBNP, increased MMP-9 and decreased LVEF were relevant risk factors and independent risk factors for heart failure in patients with different cardiac functions. NT-proBNP and MMP-9 levels are negatively correlated with LVEF in patients regardless of the cardiac function class. Therefore, attention should be paid to patients who have cardiac function in class III and above, increased NT-proBNP and MMP-9 levels and decreased LVEF in clinical practices, so as to actively prevent and treat heart failure.

Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy.

PubMed

Watanabe, Kenichi; Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Nakamura, Takashi; Nakamura, Masahiko; Harima, Meilei; Yoneyama, Hiroyuki; Suzuki, Kenji

2015-07-01

Carbohydrate sulfotransferase 15 (CHST15) is a sulfotransferase responsible for biosynthesis of chondroitin sulfate E (CS-E), which plays important roles in numerous biological events such as biosynthesis of proinflammatory cytokines. However, the effects of CHST15 siRNA in rats with chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM) have not yet been investigated. CHF was elicited in Lewis rats by immunization with cardiac myosin, and after immunization, the rats were divided into two groups and treated with either CHST15 siRNA (2μg/week) or vehicle. Age matched normal rats without immunizations were also included in this study. After 7weeks of treatment, we investigated the effects of CHST15 siRNA on cardiac function, proinflammatory cytokines, and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by CHST15 siRNA treatment in rats with CHF compared with that of vehicle-treated CHF rats. CHST15 siRNA significantly reduced cardiac fibrosis, and hypertrophy and its marker molecules (left ventricular (LV) mRNA expressions of transforming growth factor beta1, collagens I and III, and atrial natriuretic peptide) compared with vehicle-treated CHF rats. CHF-induced increased myocardial mRNA expressions of proinflammatory cytokines [interleukin (IL)-6, IL-1β], monocyte chemoattractant protein-1, and matrix metalloproteinases (MMP-2 and -9), and CHST15 were also suppressed by the treatment with CHST15 siRNA. Western blotting study has confirmed the results obtained from mRNA analysis as CHST15 siRNA treated rats expressed reduced levels of inflammatory and cardiac remodeling marker proteins. Our results demonstrate for the first time, that CHST15 siRNA treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of heart motion on parameter bias in dynamic cardiac SPECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ross, S.G.; Gullberg, G.T.; Huesman, R.H.

1996-12-31

Dynamic cardiac SPECT can be used to estimate kinetic rate parameters which describe the wash-in and wash-out of tracer activity between the blood and the myocardial tissue. These kinetic parameters can in turn be correlated to myocardial perfusion. There are, however, many physical aspects associated with dynamic SPECT which can introduce errors into the estimates. This paper describes a study which investigates the effect of heart motion on kinetic parameter estimates. Dynamic SPECT simulations are performed using a beating version of the MCAT phantom. The results demonstrate that cardiac motion has a significant effect on the blood, tissue, and backgroundmore » content of regions of interest. This in turn affects estimates of wash-in, while it has very little effect on estimates of wash-out. The effect of cardiac motion on parameter estimates appears not to be as great as effects introduced by photon noise and geometric collimator response. It is also shown that cardiac motion results in little extravascular contamination of the left ventricle blood region of interest.« less

Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-β1 pathway.

PubMed

Liu, Yan; Qi, Hanping; E, Mingyao; Shi, Pilong; Zhang, Qianhui; Li, Shuzhi; Wang, Ye; Cao, Yonggang; Chen, Yunping; Ba, Lina; Gao, Jingquan; Huang, Wei; Sun, Hongli

2018-02-01

Cardiac fibrosis is a common pathologic change along with pressure overload. Recent studies indicated that transient receptor potential (TRP) channels played multiple roles in heart. However, the functional role of transient receptor potential vanilloid-3 (TRPV3) in cardiac fibrosis remained unclear. The present study was designed to investigate the relationship between TRPV3 activation and pressure overload-induced cardiac fibrosis. Pressure overload rats were successfully established by abdominal aortic constriction (AAC), and cardiac fibrosis was simulated by 100 nM angiotensin II (Ang II) in neonatal cardiac fibroblasts. Echocardiographic parameters, cardiac fibroblast proliferation, cell cycle, intracellular calcium concentration ([Ca 2+ ] i ), and the protein expressions of collagen I, collagen III, transforming growth factor beta 1 (TGF-β 1 ), cyclin E, and cyclin-dependent kinase 2 (CDK2) were measured. Echocardiographic and histological measurements suggested that the activation of TRPV3 exacerbated the cardiac dysfunction and increased interstitial fibrosis in pressure overload rats. Further results showed that TRPV3 activation upregulated the expressions of collagen I, collagen III, TGF-β 1 , cyclin E, and CDK2 in vivo and in vitro. At the same time, blocking TGF-β 1 pathway could partially reverse the effect of TRPV3 activation. These results suggested that TRPV3 activation exacerbated cardiac fibrosis by promoting cardiac fibroblast proliferation through TGF-β 1 /CDK2/cyclin E pathway in the pressure-overloaded rat hearts.

Hemodynamic and metabolic parameters during prolonged cardiac arrest and reperfusion by extracorporeal circulation.

PubMed

Mlček, M; Ošťádal, P; Bělohlávek, J; Havránek, Š; Hrachovina, M; Huptych, M; Hála, P; Hrachovina, V; Neužil, P; Kittnar, O

2012-01-01

Extracorporeal membranous oxygenation (ECMO) is increasingly used in the management of refractory cardiac arrest. Our aim was to investigate early effects of ECMO after prolonged cardiac arrest. In fully anesthetized swine (48 kg, N=18) ventricular fibrillation (VF) was induced and untreated period (20 min) of cardiac arrest commenced, followed by 60 min extracorporeal reperfusion (ECMO flow 100 ml/kg.min). Hemodynamics, arterial blood gasses, plasma potassium, tissue oximetry (StO(2)) and cardiac (EGM) and cerebral (BIS) electrophysiological parameters were continuously recorded and analyzed. Within 3 minutes of VF hemodynamic and oximetry parameters fall abruptly while metabolic parameters destabilize gradually over 20 minutes peaking at pH 7.04 ± 0.05, pCO(2) 89 ± 14 mmHg, K(+) 8.5 ± 1.6 mmol/l. During reperfusion most parameters restore rapidly: within 3-5 minutes mean arterial pressure reaches >40 mmHg, StO(2)>50 %, paO(2)>100 mmHg, pCO(2)<50 mmHg, K(+)<5 mmol/l. EGMs mean amplitude peaks at 4.5 ± 2.4 min. Cerebral activity (BIS>60) reappeared in 5 animals after 87 ± 21 min. In 12/18 animals return of spontaneous circulation was achieved. In conclusions, ECMO provides rapid restitution of internal milieu even after prolonged arrest. However, despite normalization of global parameters full recovery was not guaranteed since cardiac and cerebral electrical activities were sufficiently restored only in some animals. More sensitive and organ specific indicators need to be identified in order to estimate adequacy of cardiac support devices.

p38 MAPK-dependent small HSP27 and αB-crystallin phosphorylation in regulation of myocardial function following cardioplegic arrest.

PubMed

Clements, Richard T; Feng, Jun; Cordeiro, Brenda; Bianchi, Cesario; Sellke, Frank W

2011-05-01

We previously demonstrated that myocardial p38 mitogen-activated protein kinase (MAPK) and heat shock protein 27 (HSP27) are phosphorylated following cardioplegic arrest in patients undergoing cardiac surgery and correlate with reduced cardiac function. The following studies were performed to determine whether inhibition of p38 MAPK and/or overexpression of nonphosphorylatable HSP27 improves cardiac function following cardioplegic arrest. Langendorff-perfused isolated rat hearts were subjected to 2 h of intermittent cold cardioplegia followed by 30 min of reperfusion. Hearts were treated with (CP+SB) or without (CP) the p38 MAPK inhibitor SB-203580 (5 μM) supplied in the cardioplegia. Sham-treated hearts served as controls. In separate experiments, isolated rat ventricular myocytes infected with either green fluorescent protein (GFP) or a nonphosphorylatable HSP27 mutant (3A-HSP27) were subjected to 3 h of cold hypoxic cardioplegia and simulated reperfusion (CP) followed by video microscopy and length change measurements. Baseline parameters of cardiac function were similar between groups [left ventricular developed pressure (LVDP), 119 ± 4.9 mmHg; positive and negative first derivatives of LV pressure (± dP/dt), 3,139 ± 245 and 2, 314 ± 110 mmHg/s]. CP resulted in reduced cardiac function (LVDP, 72.2 ± 5.8 mmHg; ± dP/dt, 2,076 ± 231 and -1,317 ± 156 mmHg/s) compared with baseline. Treatment with 5 μM SB-203580 significantly improved CP-induced cardiac function (LVDP, 101.9 ± 0 mmHg; ± dP/dt, 2,836 ± 163 and -2,108 ± 120 mmHg/s; P = 0.03, 0.01, and 0.04, CP+SB vs. CP). Inhibition of p38 MAPK significantly lowered CP-induced p38 MAPK, HSP27, and αB-crystallin (cryAB) phosphorylation. In vitro CP decreased myocyte length changes from 10.3 ± 1.5% (GFP) to 5.7 ± 0.8% (GFP+CP). Infection with 3A-HSP27 completely rescued CP-induced decreased myocyte contraction (11.1 ± 1.0%). However, infection with 3A-HSP27 did not block the endogenous HSP27 response. We conclude that inhibition of p38 MAPK and subsequent HSP27 and cryAB phosphorylation and/or overexpression of nonphosphorylatable HSP27 significantly improves cardiac performance following cardioplegic arrest. Modulation of HSP27 phosphorylation may improve myocardial stunning following cardiac surgery.

Changes in parameters of right ventricular function with cardiac resynchronization therapy.

PubMed

Sharma, Abhishek; Lavie, Carl J; Vallakati, Ajay; Garg, Akash; Goel, Sunny; Lazar, Jason; Fonarow, Gregg C

2017-11-01

Studies have shown that cardiac resynchronization therapy (CRT) significantly improves right ventricle (RV) size and function in patients with heart failure (HF). CRT does not lead to improvement in RV function independent of baseline clinical variables. A systematic search of studies published between 1966 to August 31, 2015 was conducted using Pub Med, CINAHL, Cochrane CENTRAL and the Web of Science databases. Studies reporting tricuspid annular plane systolic excursion (TAPSE) or RV basal strain or RV long axis diameter or RV short axis diameter or RV fractional area change (FAC), before and after CRT, were identified. A meta-analysis was performed using random effects with inverse variance method to determine the pooled mean difference in various parameters of RV function after CRT. Meta-regression analysis was performed to test the relationship between change in various parameters of RV functions after CRT and covariates- age, QRS duration, and left ventricular ejection fraction (LVEF). Thirteen studies (N=1541) were selected for final analysis. CRT therapy led to statistically significant increases in TAPSE [1.21 (95% CI 0.55-1.86; p<0.001)], RV FAC [2.26 (95% CI 0.50-4.01; p<0.001)] and basal strain [2.82 (95% CI 0.59-5.05; p<0.001)] and statistically significant decreases in mean RV long axis diameter [-2.94 (95% CI -5.07- -0.82; p=0.005)] and short axis diameter [-1.39 (95% CI -2.10- -0.67; p=0.876)] after a mean follow up period of 9 months. However, after meta-regression analysis for age, QRS duration, and baseline LVEF as covariates, there was no significant improvement in any of the parameters of RV function after CRT. There was a statistically significant improvement in TAPSE, RV basal strain, RV fractional area, RV long axis and short axis with CRT. However, improvement in these echocardiographic parameters of RV function after CRT was not independent of baseline clinical variables but statistically dependent on age, QRS duration and baseline LVEF. © 2017 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pecoraro, Michela; Del Pizzo, Mariagiovanna; Marzocco, Stefania

Doxorubicin (DOXO) is commonly used to treat a wide range of malignant tumors, but its clinical use is limited by acute and chronic cardiotoxicity. The precise mechanism underlying DOXO-induced cardiotoxicity is still not completely elucidated, but cardiac inflammation seems to be involved. Effects of DOXO on proinflammatory cytokines, inflammatory cell infiltration, and necrosis have been proven only when a functional impairment has already occurred, so this study aimed to investigate the acute effect of DOXO administration in mouse heart. The results of our study demonstrated alterations in cardiac function parameters assessed by ultrasound within 24 h after a single injectionmore » of DOXO, with a cumulative effect along the increase of the dose and the number of DOXO administrations. At the same time, DOXO causes a significant production of proinflammatory cytokines (such as TNF-α and IL-6) with a concomitant reduction of IL-10, a well-known antiinflammatory cytokine. Furthermore, overexpression of inducible nitric oxide synthase (iNOS) in heart tissue and increased levels of serum nitrite in DOXO-treated mice were detected. Notably, DOXO administration significantly increased nitrotyrosine expression in mouse heart. Our data support the hypothesis that these early events, could be responsible for the later onset of more severe deleterious remodeling leading to DOXO induced cardiomyopathy. - Highlights: • Doxorubicin induces echocardiographic alterations of the main cardiac functional parameters. • Doxorubicin induces increase of TNF-α and IL-6 production and iNOS expression. • Doxorubicin causes a significant reduction of the antiinflammatory cytokine IL-10. • The doses are lower than that used in human. • Doxorubicin administration significantly increased nitrotyrosine expression.« less

Dysregulated arginine metabolism and cardiopulmonary dysfunction in patients with thalassaemia.

PubMed

Morris, Claudia R; Kim, Hae-Young; Klings, Elizabeth S; Wood, John; Porter, John B; Trachtenberg, Felicia; Sweeters, Nancy; Olivieri, Nancy F; Kwiatkowski, Janet L; Virzi, Lisa; Hassell, Kathryn; Taher, Ali; Neufeld, Ellis J; Thompson, Alexis A; Larkin, Sandra; Suh, Jung H; Vichinsky, Elliott P; Kuypers, Frans A

2015-06-01

Pulmonary hypertension (PH) commonly develops in thalassaemia syndromes, but is poorly characterized. The goal of this study was to provide a comprehensive description of the cardiopulmonary and biological profile of patients with thalassaemia at risk for PH. A case-control study of thalassaemia patients at high versus low PH-risk was performed. A single cross-sectional measurement for variables reflecting cardiopulmonary status and biological pathophysiology were obtained, including Doppler-echocardiography, 6-min-walk-test, Borg Dyspnoea Score, New York Heart Association functional class, cardiac magnetic resonance imaging (MRI), chest-computerized tomography, pulmonary function testing and laboratory analyses targeting mechanisms of coagulation, inflammation, haemolysis, adhesion and the arginine-nitric oxide pathway. Twenty-seven thalassaemia patients were evaluated, 14 with an elevated tricuspid-regurgitant-jet-velocity (TRV) ≥ 2·5 m/s. Patients with increased TRV had a higher frequency of splenectomy, and significantly larger right atrial size, left atrial volume and left septal-wall thickness on echocardiography and/or MRI, with elevated biomarkers of abnormal coagulation, lactate dehydrogenase (LDH) levels and arginase concentration, and lower arginine-bioavailability compared to low-risk patients. Arginase concentration correlated significantly to several echocardiography/MRI parameters of cardiovascular function in addition to global-arginine-bioavailability and biomarkers of haemolytic rate, including LDH, haemoglobin and bilirubin. Thalassaemia patients with a TRV ≥ 2·5 m/s have additional echocardiography and cardiac-MRI parameters suggestive of right and left-sided cardiac dysfunction. In addition, low arginine bioavailability may contribute to cardiopulmonary dysfunction in β-thalassaemia. © 2015 John Wiley & Sons Ltd.

Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.

PubMed

Bondanelli, Marta; Bonadonna, Stefania; Ambrosio, Maria Rosaria; Doga, Mauro; Gola, Monica; Onofri, Alessandro; Zatelli, Maria Chiara; Giustina, Andrea; degli Uberti, Ettore C

2005-09-01

Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (P<.05) in patients with gigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocity<1) was detected in 2 of 6 patients with gigantism and 1 of 6 patients with acromegaly. Impaired glucose metabolism occurrence was higher in patients with acromegaly (66%) compared with patients with gigantism (16%). Concentrations of IGF-I were significantly (P<.05) higher in patients with gigantism who have cardiac abnormalities than in those without cardiac abnormalities. In conclusion, our data suggest that GH/IGF-I excess in young adult patients is associated with morphologic and functional cardiac abnormalities that are similar in patients with gigantism and in patients with acromegaly, whereas occurrence of impaired glucose metabolism appears to be higher in patients with acromegaly, although patients with gigantism are exposed to GH excess for a longer period.

Estimating cardiac fiber orientations in pig hearts using registered ultrasound and MR image volumes

NASA Astrophysics Data System (ADS)

Dormer, James D.; Meng, Yuguang; Zhang, Xiaodong; Jiang, Rong; Wagner, Mary B.; Fei, Baowei

2017-03-01

Heart fiber mechanics can be important predictors in current and future cardiac function. Accurate knowledge of these mechanics could enable cardiologists to provide a diagnosis before conditions progress. Magnetic resonance diffusion tensor imaging (MR-DTI) has been used to determine cardiac fiber orientations. Ultrasound is capable of providing anatomical information in real time, enabling a physician to quickly adjust parameters to optimize image scans. If known fiber orientations from a template heart measured using DTI can be accurately deformed onto a cardiac ultrasound volume, fiber orientations could be estimated for the patient without the need for a costly MR scan while still providing cardiologists valuable information about the heart mechanics. In this study, we apply the method to pig hearts, which are a close representation of human heart anatomy. Experiments from pig hearts show that the registration method achieved an average Dice similarity coefficient (DSC) of 0.819 +/- 0.050 between the ultrasound and deformed MR volumes and that the proposed ultrasound-based method is able to estimate the cardiac fiber orientation in pig hearts.

Andrographis paniculata extract protect against isoproterenol-induced myocardial injury by mitigating cardiac dysfunction and oxidative injury in rats.

PubMed

Ojha, Shreesh; Bharti, Saurabh; Golechha, Mahaveer; Sharma, Ashok K; Rani, Neha; Kumari, Santosh; Arya, Dharamvir Singh

2012-01-01

Present study evaluated the cardioprotective effect of Andrographis paniculata (100, 200 or 400 mg/kg) against isoproterenol (85 mg/kg, b.w.)-induced cardiotoxicity referred as myocardial infarction in rats. Isoproterenol significantly (p < 0.05) decreased mean arterial pressure, heart rate, contractility and relaxation and increased left ventricular end diastolic pressure. Isoproterenol also significantly (p < 0.05) decreased antioxidants, superoxide dismutase, catalase, glutathione peroxidase, glutathione and increased leakage of cardiac injury markers; creatine phosphokinase-MB isoenzyme, lactate dehydrogenase concomitant to increased lipid peroxidation and histopathological perturbations. However, pretreatment with A. paniculata favorably restored hemodynamic parameters and left ventricular function and significantly (p < 0.05) prevented the depletion of endogenous antioxidants and myocyte marker enzymes as well as inhibited lipid peroxidation. Significant (p < 0.05) reversal of almost all the hemodynamic, biochemical and histopathological parameters by A. paniculata pretreatment in isoproterenol-induced cardiotoxicity depicted the cardioprotective effect of A. paniculata. Results showed that A. paniculata protected heart against cardiotoxic effects of isoproterenol by boosting endogenous antioxidant network, restoring ventricular function and maintaining structural integrity of heart.

Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure.

PubMed

Ikeda, Yuki; Ishii, Shunsuke; Fujita, Teppei; Iida, Yuichiro; Kaida, Toyoji; Nabeta, Takeru; Maekawa, Emi; Yanagisawa, Tomoyoshi; Koitabashi, Toshimi; Takeuchi, Ichiro; Inomata, Takayuki; Ako, Junya

2017-03-01

Intestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients. Abdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E' ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes. In hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes. Copyright © 2016. Published by Elsevier B.V.

Equivalent cardioprotection induced by ischemic and hypoxic preconditioning.

PubMed

Xiang, Xujin; Lin, Haixia; Liu, Jin; Duan, Zeyan

2013-04-01

We aimed to compare cardioprotection induced by various hypoxic preconditioning (HPC) and ischemic preconditioning (IPC) protocols. Isolated rat hearts were randomly divided into 7 groups (n = 7 per group) and received 3 or 5 cycles of 3-minute ischemia or hypoxia followed by 3-minute reperfusion (IPC33 or HPC33 or IPC53 or HPC53 group), 3 cycles of 5-minute ischemia or hypoxia followed by 5-minute reperfusion (IPC35 group or HPC35 group), or 30-minute perfusion (ischemic/reperfusion group), respectively. Then all the hearts were subjected to 50-minute ischemia and 120-minute reperfusion. Cardiac function, infarct size, and coronary flow rate (CFR) were evaluated. Recovery of cardiac function and CFR in IPC35, HPC35, and HPC53 groups was significantly improved as compared with I/R group (p < 0.01). There were no significant differences in cardiac function parameters between IPC35 and HPC35 groups. Consistently, infarct size was significantly reduced in IPC35, HPC35, and HPC53 groups compared with ischemic/reperfusion group. Multiple-cycle short duration HPC exerted cardioprotection, which was as powerful as that of IPC. Georg Thieme Verlag KG Stuttgart · New York.

The role of mineral and bone disorders in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus of long duration.

PubMed

Biragova, Margarita S; Gracheva, Svetlana A; Glazunova, Alexandra M; Martynov, Sergey A; Ulaynova, Irina N; Ilyin, Alexandr V; Philippov, Yury I; Musaeva, Guliya M; Shamkhalova, Minara S; Shestakova, Marina V

2016-08-01

The objective of our study was to evaluate the role of mineral and bone metabolism disorders associated with chronic kidney disease (MBD-CKD) in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus (T1DM) of long duration. We investigated 96 patients with T1DM of long duration, with CKD at different stages (0-5), including patients on hemodialysis (HD) and with kidney transplantation (KT). Along with overall clinical examination, we assessed markers of MBD (calcium, phosphorus, parathormone, vitamin D, fibroblast growth factor (FGF) 23) and levels of cardiac injury marker (atrial natriuretic peptide, NT-proBNP). Multispiral computer tomography with Agatston index calculation was also included. Decreased kidney function was associated with increased of levels phosphorus, parathormone, FGF 23, and vitamin D deficiency, with the highest deviation from the reference ranges seen in patients on HD with a very high risk of cardiovascular events. In KT patients with satisfactory graft function, these parameters were at the same levels as in patients with CKD stages 0-4. Progression of cardiovascular pathology was accompanied by elevation of NT-proBNP levels as CKD duration increased, decreased glomerular filtration rate, and were correlated with the main parameters of mineral homeostasis. The severity of coronary arteries calcification was associated with patient age and duration of T1DM and arterial hypertension. Development and progression of kidney dysfunction is accompanied by MBD, a significant factor in progression of cardiac pathology, which remains a major cause of mortality in this patient population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

TRPV2 knockout mice demonstrate an improved cardiac performance following myocardial infarction due to attenuated activity of peri-infarct macrophages.

PubMed

Entin-Meer, Michal; Cohen, Lena; Hertzberg-Bigelman, Einat; Levy, Ran; Ben-Shoshan, Jeremy; Keren, Gad

2017-01-01

We have recently shown that the expression of the transient receptor potential vanilloid 2 channel, TRPV2, is upregulated in the peri-infarct zone 3-5 days following an acute myocardial infarction (AMI). Further analysis has demonstrated that invading monocytes maturing to macrophages merely harbor the documented elevated expression of this channel. Assess cardiac function in TRPV2-KO mice compared to TRPV2-WT following AMI and analyze the potential involvement of TRPV2-expressing macrophages in the recovery process. TRPV2-KO or WT mice were induced with AMI by ligation of the left anterior descending artery (LAD). In another set of experiments, TRPV2-KO mice induced with AMI, were intravenously (IV) injected with WT or TRPV2-KO peritoneal macrophages in order to directly assess the potential contribution of TRPV2-expressing macrophages to cardiac healing. Cardiac parameters were obtained by echocardiography 1 day and 30 days post infarction. The relative changes in the ejection fraction (EF) and additional cardiac parameters between baseline (day 1) and day 30 were calculated and statistical significance was determined (SPSS). The in vivo study showed that while EF was significantly decreased in the WT animals between baseline and day 30, EF was only slightly and insignificantly reduced in the KO animals. Likewise LVESD and LVESA were significantly modified exclusively in the WT animals. Moreover, intravenous administration of peritoneal WT macrophages, but not KO macrophages, significantly reduced survival of post-MI TRPV2-KO mice. The data suggest that knockout of the TRPV2 channel may attenuate macrophage-dependent pro-inflammatory processes and result in better cardiac recovery. TRPV2 may thus represent a novel therapeutic target for treatment of patients undergoing an acute MI.

Left atrial phasic function and heart rate variability in asymptomatic diabetic patients.

PubMed

Tadic, Marijana; Vukomanovic, Vladan; Cuspidi, Cesare; Suzic-Lazic, Jelena; Stanisavljevic, Dejana; Celic, Vera

2017-03-01

We evaluated left atrial (LA) phasic function and heart rate variability (HRV) in asymptomatic diabetic patients, and the relationship between HRV indices and LA phasic function assessed by volumes and speckle tracking imaging. This cross-sectional study included 55 asymptomatic patients with type 2 diabetes and 50 healthy controls without cardiovascular risk factors. All study subjects underwent laboratory analyses, complete two-dimensional echocardiography examination (2DE) and 24-h Holter monitoring. Maximum, minimum LA and pre-A LA volumes and volume indexes are significantly higher in diabetic patients. Total and passive LA emptying fractions (EF), representing the LA reservoir and conduit function, are significantly lower in diabetic subjects. Active LA EF, the parameter of the LA booster pump function, is compensatory increased in diabetic patients. Similar results were obtained by 2DE strain analysis. Cardiac autonomic function, assessed by HRV, is significantly deteriorated in diabetic patients. Time and frequency-domain HRV measures are significantly lower in diabetic subjects than in controls. HbA1c, LV mass index and HRV are associated with total LA EF and longitudinal LA strain independently of age, body mass index and LV diastolic function in the whole study population. LA phasic function and cardiac autonomic nervous system assessed by HRV are impacted by diabetes. HbA1c and HRV are independently associated with LA reservoir function evaluated by volumetric and strain methods in the whole study population. This study emphasizes the importance of determination of LA function and HRV as important markers of preclinical cardiac damage and autonomic function impairment in diabetic patients.

Sodium Butyrate Protects -Against High Fat Diet-Induced Cardiac Dysfunction and Metabolic Disorders in Type II Diabetic Mice.

PubMed

Zhang, Ling; Du, Jianfeng; Yano, Naohiro; Wang, Hao; Zhao, Yu Tina; Dubielecka, Patrycja M; Zhuang, Shougang; Chin, Y Eugene; Qin, Gangjian; Zhao, Ting C

2017-08-01

Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in Type II diabetes and obesity remains unknown. Here, we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively. Glucose intolerance, metabolic parameters, cardiac function, and remodeling were assessed. Histological analysis and cellular signaling were examined at 24 weeks following euthanization of mice. HFD-fed mice demonstrated myocardial dysfunction and profound interstitial fibrosis, which were attenuated by HDAC inhibition. HFD-induced metabolic syndrome features insulin resistance, obesity, hyperinsulinemia, hyperglycemia, lipid accumulations, and cardiac hypertrophy, these effects were prevented by HDAC inhibition. Furthermore, HDAC inhibition attenuated myocyte apoptosis, reduced production of reactive oxygen species, and increased angiogenesis in the HFD-fed myocardium. Notably, HFD induced decreases in MKK3, p38, p38 regulated/activated protein kinase (PRAK), and Akt-1, but not p44/42 phosphorylation, which were prevented by HDAC inhibition. These results suggest that HDAC inhibition plays a critical role to preserve cardiac performance and mitigate metabolic disorders in obesity and diabetes, which is associated with MKK3/p38/PRAK pathway. The study holds promise in developing a new therapeutic strategy in the treatment of Type II diabetic-induced heart failure and metabolic disorders. J. Cell. Biochem. 118: 2395-2408, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

[The use of controlled physical training in patients with acute coronary syndrome treated with intervention - assessment of effects on biochemical parameters and functional myocardial].

PubMed

Kapusta, Joanna; Kapusta, Anna; Pawlicki, Lucjan; Irzmański, Robert

2016-06-01

Diseases of the cardiovascular system is one of the most common causes of death among people over 65 years. Due to its course and incidence are a major cause of disability and impaired quality of life for seniors, as well as a serious economic problem in health care. Important role in the prevention of cardiovascular disease plays making systematic physical activity, which is a component of any rehabilitation program. Regular physical training by doing cardio-and vasoprotective has a beneficial effect on cardiovascular status and physical performance in patients with diagnosed coronary heart disease, regardless of age. The aim of this study was to evaluate the effect of controlled exercise on selected biochemical parameters and functional myocardial infarction. A group of 89 patients were divided into 3 subgroups. In group I (n = 30) was performed 2 weeks cardiac rehabilitation program, in group II (n = 30) 4 weekly. Streamline the program consisted of a series of interval training performed using a bicycle ergometer and general exercise. The remaining group (gr. III, n = 29) participated in individually selected training program. In all subjects before and after the training cycle underwent thoracic impedance plethysmography, also determined the level of plasma natriuretic peptide NT-proBNP and echocardiography and exercise test. After training, in groups, which carried out a controlled physical training, improvement was observed: exercise capacity of patients respectively in group I (p = 0.0003), group II (p = 0.0001) and group III (p = 0.032), stroke volume SV, cardiac output CO and global myocardial contractility, there was also reduction in the concentration of natriuretic peptide NT-proBNP. Furthermore, the correlation between the results shown pletyzmography parameters and NT-proBNP, SV, CO and EF. Regular physical training as part of the cardiac rehabilitation has a beneficial effect on biochemical parameters and functional myocardial infarction in patients with ACS. Size of the observed changes conditioned by the nature and duration of the training. © 2016 MEDPRESS.

Evolution of echocardiography in subclinical detection of cancer therapy-related cardiac dysfunction.

PubMed

Moudgil, Rohit; Hassan, Saamir; Palaskas, Nicolas; Lopez-Mattei, Juan; Banchs, Jose; Yusuf, Syed Wamique

2018-05-11

Cancer therapies have resulted in increased survivorship in oncological patients. However, the benefits have been marred by the development of premature cardiovascular disease. The current definition outlines measurement of ejection fraction as a mean to diagnose cancer therapeutic-related cardiac dysfunction (CTRCD); however, up to 58% of the patients do not regain their cardiac function after the CTRCD diagnosis, despite therapeutic interventions. Therefore, there has been a growing interest in the markers for early myocardial changes (ie, changes with normal left ventricular ejection fraction [LVEF]) that may predict the development of subsequent left ventricular ejection fraction reduction or progression to heart failure. This review will highlight the use of diastolic parameters, tissue Doppler imaging (TDI), and speckle tracking echocardiogram (STE) as emerging technologies which can potentially detect cardiac dysfunction thereby stratifying patients for cardioprotective therapies. The goal of this manuscript was to highlight the concepts and discuss the current controversies surrounding these echocardiographic imaging modalities. © 2018 Wiley Periodicals, Inc.

Current Status of 3-Dimensional Speckle Tracking Echocardiography: A Review from Our Experiences

PubMed Central

Ishizu, Tomko; Aonuma, Kazutaka

2014-01-01

Cardiac function analysis is the main focus of echocardiography. Left ventricular ejection fraction (LVEF) has been the clinical standard, however, LVEF is not enough to investigate myocardial function. For the last decade, speckle tracking echocardiography (STE) has been the novel clinical tool for regional and global myocardial function analysis. However, 2-dimensional imaging methods have limitations in assessing 3-dimensional (3D) cardiac motion. In contrast, 3D echocardiography also has been widely used, in particular, to measure LV volume measurements and assess valvular diseases. Joining the technology bandwagon, 3D-STE was introduced in 2008. Experimental studies and clinical investigations revealed the reliability and feasibility of 3D-STE-derived data. In addition, 3D-STE provides a novel deformation parameter, area change ratio, which have the potential for more accurate assessment of overall and regional myocardial function. In this review, we introduced the features of the methodology, validation, and clinical application of 3D-STE based on our experiences for 7 years. PMID:25031794

Linking an Anxiety-Related Personality Trait to Cardiac Autonomic Regulation in Well-Defined Healthy Adults: Harm Avoidance and Resting Heart Rate Variability.

PubMed

Kao, Lien-Cheng; Liu, Yu-Wen; Tzeng, Nian-Sheng; Kuo, Terry B J; Huang, San-Yuan; Chang, Chuan-Chia; Chang, Hsin-An

2016-07-01

Anxiety trait, anxiety and depression states have all been reported to increase risks for cardiovascular disease (CVD), possibly through altering cardiac autonomic regulation. Our aim was to investigate whether the relationship between harm avoidance (HA, an anxiety-related personality trait) and cardiac autonomic regulation is independent of anxiety and depression states in healthy adults. We recruited 535 physically and mentally healthy volunteers. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Tri-dimensional Personality Questionnaire. Participants were divided into high or low HA groups as discriminated by the quartile value. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV). We obtained the time and frequency-domain indices of HRV including variance (total HRV), the low-frequency power (LF; 0.05-0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. The BDI and HA scores showed associations with HRV parameters. After adjustment for the BDI scores and other control variables, HA is still associated with reduced variance, LF and HF power. Compared with the participants with low HA, those with high HA displayed significant reductions in variance, LF and HF power and a significant increase in their LF/HF ratio. This study highlights the independent role of HA in contributing to decreased autonomic cardiac regulation in healthy adults and provides a potential underlying mechanism for anxiety trait to confer increased risk for CVD.

Cardiovascular haemodynamics and cardiac autonomic control in patients with subclinical and overt hyperthyroidism.

PubMed

Petretta, M; Bonaduce, D; Spinelli, L; Vicario, M L; Nuzzo, V; Marciano, F; Camuso, P; De Sanctis, V; Lupoli, G

2001-12-01

To characterize cardiac structure and function and cardiac autonomic control in patients with subclinical and overt hyperthyroidism. Thirty patients with subclinical hyperthyroidism and 30 with overt disease were selected from patients never previously treated for endocrinological disease in the outpatient clinic of our institution. Twenty normal individuals were studied as control group. Left ventricular structure and function and cardiac autonomic control were evaluated, respectively, by two-dimensional Doppler echocardiography and by 24-h Holter recording with heart rate variability analysis. Patients with overt hyperthyroidism showed greater values of left ventricular end-diastolic volume (P<0.05) and left ventricular mass (P<0.05) than patients with subclinical disease. In addition, the mean velocity of left ventricular fibre shortening (P<0.05) and left ventricular ejection fraction (P<0.05) were greater in patients with overt hyperthyroidism than in patients with subclinical disease. No difference in any of these parameters was detectable between normal subjects and patients with subclinical disease. The isovolumic relaxation period was shorter in patients with subclinical hyperthyroidism than in control individuals (P<0.05) and in patients with overt hyperthyroidism (P<0.05). As regards cardiac autonomic control, all time and frequency domain measures decreased progressively from control individuals to patients with subclinical hyperthyroidism and those with overt disease (P<0.001). Thyrotoxic patients show changes in left ventricular structure and increased echocardiographic indexes of myocardial contractility, whereas the only echocardiographic feature detectable in patients with subclinical hyperthyroidism is an increased velocity of left ventricular relaxation. Cardiac parasympathetic withdrawal is evident in patients with overt hyperthyroidism and in patients with subclinical disease.

Linking an Anxiety-Related Personality Trait to Cardiac Autonomic Regulation in Well-Defined Healthy Adults: Harm Avoidance and Resting Heart Rate Variability

PubMed Central

Kao, Lien-Cheng; Liu, Yu-Wen; Tzeng, Nian-Sheng; Kuo, Terry B. J.; Huang, San-Yuan

2016-01-01

Objective Anxiety trait, anxiety and depression states have all been reported to increase risks for cardiovascular disease (CVD), possibly through altering cardiac autonomic regulation. Our aim was to investigate whether the relationship between harm avoidance (HA, an anxiety-related personality trait) and cardiac autonomic regulation is independent of anxiety and depression states in healthy adults. Methods We recruited 535 physically and mentally healthy volunteers. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Tri-dimensional Personality Questionnaire. Participants were divided into high or low HA groups as discriminated by the quartile value. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV). We obtained the time and frequency-domain indices of HRV including variance (total HRV), the low-frequency power (LF; 0.05–0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15–0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. Results The BDI and HA scores showed associations with HRV parameters. After adjustment for the BDI scores and other control variables, HA is still associated with reduced variance, LF and HF power. Compared with the participants with low HA, those with high HA displayed significant reductions in variance, LF and HF power and a significant increase in their LF/HF ratio. Conclusion This study highlights the independent role of HA in contributing to decreased autonomic cardiac regulation in healthy adults and provides a potential underlying mechanism for anxiety trait to confer increased risk for CVD. PMID:27482240

Cardiac function and cognition in older community-dwelling cardiac patients.

PubMed

Eggermont, Laura H P; Aly, Mohamed F A; Vuijk, Pieter J; de Boer, Karin; Kamp, Otto; van Rossum, Albert C; Scherder, Erik J A

2017-11-01

Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test. Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies. © 2017 Japanese Psychogeriatric Society.

Congestive renal failure: the pathophysiology and treatment of renal venous hypertension.

PubMed

Ross, Edward A

2012-12-01

Longstanding experimental evidence supports the role of renal venous hypertension in causing kidney dysfunction and "congestive renal failure." A focus has been heart failure, in which the cardiorenal syndrome may partly be due to high venous pressure, rather than traditional mechanisms involving low cardiac output. Analogous diseases are intra-abdominal hypertension and renal vein thrombosis. Proposed pathophysiologic mechanisms include reduced transglomerular pressure, elevated renal interstitial pressure, myogenic and neural reflexes, baroreceptor stimulation, activation of sympathetic nervous and renin angiotensin aldosterone systems, and enhanced proinflammatory pathways. Most clinical trials have addressed the underlying condition rather than venous hypertension per se. Interpreting the effects of therapeutic interventions on renal venous congestion are therefore problematic because of such confounders as changes in left ventricular function, cardiac output, and blood pressure. Nevertheless, there is preliminary evidence from small studies of intense medical therapy or extracorporeal ultrafiltration for heart failure that there can be changes to central venous pressure that correlate inversely with renal function, independently from the cardiac index. Larger more rigorous trials are needed to definitively establish under what circumstances conventional pharmacologic or ultrafiltration goals might best be directed toward central venous pressures rather than left ventricular or cardiac output parameters. Copyright © 2012 Elsevier Inc. All rights reserved.

Critical Care Management Focused on Optimizing Brain Function After Cardiac Arrest.

PubMed

Nakashima, Ryuta; Hifumi, Toru; Kawakita, Kenya; Okazaki, Tomoya; Egawa, Satoshi; Inoue, Akihiko; Seo, Ryutaro; Inagaki, Nobuhiro; Kuroda, Yasuhiro

2017-03-24

The discussion of neurocritical care management in post-cardiac arrest syndrome (PCAS) has generally focused on target values used for targeted temperature management (TTM). There has been less attention paid to target values for systemic and cerebral parameters to minimize secondary brain damage in PCAS. And the neurologic indications for TTM to produce a favorable neurologic outcome remain to be determined. Critical care management of PCAS patients is fundamental and essential for both cardiologists and general intensivists to improve neurologic outcome, because definitive therapy of PCAS includes both special management of the cause of cardiac arrest, such as coronary intervention to ischemic heart disease, and intensive management of the results of cardiac arrest, such as ventilation strategies to avoid brain ischemia. We reviewed the literature and the latest research about the following issues and propose practical care recommendations. Issues are (1) prediction of TTM candidate on admission, (2) cerebral blood flow and metabolism and target value of them, (3) seizure management using continuous electroencephalography, (4) target value of hemodynamic stabilization and its method, (5) management and analysis of respiration, (6) sedation and its monitoring, (7) shivering control and its monitoring, and (8) glucose management. We hope to establish standards of neurocritical care to optimize brain function and produce a favorable neurologic outcome.

Heart rate variability in normal-weight patients with polycystic ovary syndrome.

PubMed

Kilit, Celal; Paşalı Kilit, Türkan

2017-05-01

Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors of cardiovascular disease. Obese women with PCOS show altered autonomic modulation. The results of studies investigating cardiac autonomic functions of normal-weight women with PCOS are conflicting. The aim of the study was to assess the reactivity of cardiac sympathovagal balance in normal-weight women with PCOS by heart rate variability analysis. We examined the heart rate variability in 60 normal-weight women with PCOS and compared them with that in 60 age-matched healthy women having a similar metabolic profile. Time and frequency domain parameters of heart rate variability were analyzed based on 5-min-long continuous electrocardiography recordings for the following 3 periods: (1) during rest in supine position, (2) during controlled breathing, and (3) during isometric handgrip exercise. Time and frequency domain parameters of heart rate variability for the 3 periods assessed were similar in the two groups. Although modified Ferriman-Gallwey score and serum testosterone and luteinizing hormone levels were significantly higher in women with PCOS, homeostatic model assessment-insulin resistance (HOMA-IR) was not different the between the PCOS and control groups. There were no significant correlations between serum testosterone levels and heart rate variability parameters among the study population. The findings of this study suggest that the reactivity of cardiac sympathovagal balance is not altered in normal-weight women with PCOS having a normal HOMA-IR.

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

PubMed

Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

High-throughput cardiac science on the Grid.

PubMed

Abramson, David; Bernabeu, Miguel O; Bethwaite, Blair; Burrage, Kevin; Corrias, Alberto; Enticott, Colin; Garic, Slavisa; Gavaghan, David; Peachey, Tom; Pitt-Francis, J; Pueyo, E; Rodriguez, Blanca; Sher, Anna; Tan, Jefferson

2010-08-28

Cardiac electrophysiology is a mature discipline, with the first model of a cardiac cell action potential having been developed in 1962. Current models range from single ion channels, through very complex models of individual cardiac cells, to geometrically and anatomically detailed models of the electrical activity in whole ventricles. A critical issue for model developers is how to choose parameters that allow the model to faithfully reproduce observed physiological effects without over-fitting. In this paper, we discuss the use of a parametric modelling toolkit, called Nimrod, that makes it possible both to explore model behaviour as parameters are changed and also to tune parameters by optimizing model output. Importantly, Nimrod leverages computers on the Grid, accelerating experiments by using available high-performance platforms. We illustrate the use of Nimrod with two case studies, one at the cardiac tissue level and one at the cellular level.

Right ventricular dyssynchrony in idiopathic pulmonary arterial hypertension: determinants and impact on pump function.

PubMed

Badagliacca, Roberto; Poscia, Roberto; Pezzuto, Beatrice; Papa, Silvia; Gambardella, Cristina; Francone, Marco; Mezzapesa, Mario; Nocioni, Martina; Nona, Alfred; Rosati, Riccardo; Sciomer, Susanna; Fedele, Francesco; Dario Vizza, Carmine

2015-03-01

Right ventricular (RV) dyssynchrony has been described in pulmonary arterial hypertension (PAH), but no evidence is available on its morphologic determinants and its effect on systolic function. The aim of this study was to evaluate the morphologic determinants of RV dyssynchrony by echocardiographic and cardiac magnetic resonance imaging and its effect on systolic function. In 60 consecutive idiopathic PAH (IPAH) patients with narrow QRS, RV dyssynchrony was evaluated by 2D speckle-tracking echocardiography, calculating the standard deviation of the times to peak systolic strain for the four mid-basal RV segments (RV-SD4). Patients were grouped by the median value of RV-SD4 (19 milliseconds) and compared for RV remodeling and systolic function parameters, WHO class, pulmonary hemodynamics and 6-minute walk test (6MWT). Despite similar pulmonary vascular resistance and mean pulmonary arterial pressure, patients with RV-SD4 at >19 milliseconds had advanced WHO class and worse 6MWT, RV hemodynamics, RV remodeling and systolic function parameters compared with patients at ≤19 milliseconds. The morphologic determinants of RV dyssynchrony resulted RV end-diastolic area, LV diastolic eccentricity index and RV mass volume ratio (r = 0.69, r(2) = 0.47, p < 0.0001). Finally, we found a significant inverse correlation between RV mid-basal segments post-systolic shortening time and cardiac index (r = -0.64, r(2) = 0.41, p = 0.001), accounting for the significant correlation between RV-SD4 and cardiac index (r = 0.57, r(2) = 0.32, p = 0.003). In IPAH with narrow QRS, RV dyssynchrony is associated with RV dilation and eccentric hypertrophy pattern, suggesting a role of segmental wall stress heterogeneity as the major determinant of mechanical delay. Post-systolic shortening, as inefficient contraction, contributes to pump dysfunction. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Detrended Fluctuation Analysis of Heart Rate Dynamics Is an Important Prognostic Factor in Patients with End-Stage Renal Disease Receiving Peritoneal Dialysis

PubMed Central

Lin, Lian-Yu; Chang, Chin-Hao; Chu, Fang-Ying; Lin, Yen-Hung; Wu, Cho-Kai; Lee, Jen-Kuang; Hwang, Juei-Jen; Lin, Jiunn-Lee; Chiang, Fu-Tien

2016-01-01

Background and Objectives Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. Materials and Methods Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated. Results A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617–0.905). DFAα1≧ 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007–0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033–0.362, P = 0.0003). Conclusion Cardiac autonomic dysfunction evaluated by DFAα1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD. PMID:26828209

Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction.

PubMed

Unger, Erin D; Dubin, Ruth F; Deo, Rajat; Daruwalla, Vistasp; Friedman, Julie L; Medina, Crystal; Beussink, Lauren; Freed, Benjamin H; Shah, Sanjiv J

2016-01-01

Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF. We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064). In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes. NCT01030991. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Cardiac injury biomarkers in paediatric age: Are we there yet?

PubMed

Neves, Ana L; Henriques-Coelho, Tiago; Leite-Moreira, Adelino; Areias, José C

2016-11-01

The aim of this article is to evaluate the clinical utility of cardiac injury biomarkers in paediatric age. In December 2015, a literature search was performed (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included the following medical subject headings and text terms for the key words: "cardiac injury biomarkers", "creatine kinase-MB", "myoglobin", "troponin", "children", "neonate/s", "newborn/s", "infant/s" and echocardiography. In the paediatric population, troponins show a good correlation with the extent of myocardial damage following cardiac surgery and cardiotoxic medication and can be used as predictors of subsequent cardiac recovery and mortality. Elevation of cardiac injury biomarkers may also have diagnostic value in cases when cardiac contusion or pericarditis is suspected. Cardiac injury biomarkers are very sensitive markers for the detection of myocardial injury and have been studied in healthy newborns, after tocolysis, intrauterine growth restriction, respiratory distress and asphyxia. The proportion of newborns with elevated troponin was higher than that in ill infants, children, and adolescents and in healthy adults, suggesting that myocardial injury, although clinically occult, is common in this young age group. Results suggest that significant elevation of cord troponin is an excellent early predictor of severity of hypoxic-ischaemic encephalopathy and mortality in term infants. Cardiac biomarkers may also benefit centres without on-site echocardiography with evidence showing good correlation with echo-derived markers of myocardial function. Further studies are needed to better clarify the role of cardiac biomarkers in paediatric age and their correlation with echocardiographic parameters.

Improved hepatic arterial fraction estimation using cardiac output correction of arterial input functions for liver DCE MRI

NASA Astrophysics Data System (ADS)

Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

2017-02-01

Liver dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling could be useful in the assessment of diffuse liver disease and focal liver lesions, but is compromised by errors in arterial input function (AIF) sampling. In this study, we apply cardiac output correction to arterial input functions (AIFs) for liver DCE MRI and investigate the effect on dual-input single compartment hepatic perfusion parameter estimation and reproducibility. Thirteen healthy volunteers (28.7  ±  1.94 years, seven males) underwent liver DCE MRI and cardiac output measurement using aortic root phase contrast MRI (PCMRI), with reproducibility (n  =  9) measured at 7 d. Cardiac output AIF correction was undertaken by constraining the first pass AIF enhancement curve using the indicator-dilution principle. Hepatic perfusion parameters with and without cardiac output AIF correction were compared and 7 d reproducibility assessed. Differences between cardiac output corrected and uncorrected liver DCE MRI portal venous (PV) perfusion (p  =  0.066), total liver blood flow (TLBF) (p  =  0.101), hepatic arterial (HA) fraction (p  =  0.895), mean transit time (MTT) (p  =  0.646), distribution volume (DV) (p  =  0.890) were not significantly different. Seven day corrected HA fraction reproducibility was improved (mean difference 0.3%, Bland-Altman 95% limits-of-agreement (BA95%LoA)  ±27.9%, coefficient of variation (CoV) 61.4% versus 9.3%, ±35.5%, 81.7% respectively without correction). Seven day uncorrected PV perfusion was also improved (mean difference 9.3 ml min-1/100 g, BA95%LoA  ±506.1 ml min-1/100 g, CoV 64.1% versus 0.9 ml min-1/100 g, ±562.8 ml min-1/100 g, 65.1% respectively with correction) as was uncorrected TLBF (mean difference 43.8 ml min-1/100 g, BA95%LoA  ±586.7 ml min-1/ 100 g, CoV 58.3% versus 13.3 ml min-1/100 g, ±661.5 ml min-1/100 g, 60.9% respectively with correction). Reproducibility of uncorrected MTT was similar (uncorrected mean difference 2.4 s, BA95%LoA  ±26.7 s, CoV 60.8% uncorrected versus 3.7 s, ±27.8 s, 62.0% respectively with correction), as was and DV (uncorrected mean difference 14.1%, BA95%LoA  ±48.2%, CoV 24.7% versus 10.3%, ±46.0%, 23.9% respectively with correction). Cardiac output AIF correction does not significantly affect the estimation of hepatic perfusion parameters but demonstrates improvements in normal volunteer 7 d HA fraction reproducibility, but deterioration in PV perfusion and TLBF reproducibility. Improved HA fraction reproducibility maybe important as arterialisation of liver perfusion is increased in chronic liver disease and within malignant liver lesions.

Comparison among Reconstruction Algorithms for Quantitative Analysis of 11C-Acetate Cardiac PET Imaging.

PubMed

Shi, Ximin; Li, Nan; Ding, Haiyan; Dang, Yonghong; Hu, Guilan; Liu, Shuai; Cui, Jie; Zhang, Yue; Li, Fang; Zhang, Hui; Huo, Li

2018-01-01

Kinetic modeling of dynamic 11 C-acetate PET imaging provides quantitative information for myocardium assessment. The quality and quantitation of PET images are known to be dependent on PET reconstruction methods. This study aims to investigate the impacts of reconstruction algorithms on the quantitative analysis of dynamic 11 C-acetate cardiac PET imaging. Suspected alcoholic cardiomyopathy patients ( N = 24) underwent 11 C-acetate dynamic PET imaging after low dose CT scan. PET images were reconstructed using four algorithms: filtered backprojection (FBP), ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), and OSEM with both time-of-flight and point-spread-function (TPSF). Standardized uptake values (SUVs) at different time points were compared among images reconstructed using the four algorithms. Time-activity curves (TACs) in myocardium and blood pools of ventricles were generated from the dynamic image series. Kinetic parameters K 1 and k 2 were derived using a 1-tissue-compartment model for kinetic modeling of cardiac flow from 11 C-acetate PET images. Significant image quality improvement was found in the images reconstructed using iterative OSEM-type algorithms (OSME, TOF, and TPSF) compared with FBP. However, no statistical differences in SUVs were observed among the four reconstruction methods at the selected time points. Kinetic parameters K 1 and k 2 also exhibited no statistical difference among the four reconstruction algorithms in terms of mean value and standard deviation. However, for the correlation analysis, OSEM reconstruction presented relatively higher residual in correlation with FBP reconstruction compared with TOF and TPSF reconstruction, and TOF and TPSF reconstruction were highly correlated with each other. All the tested reconstruction algorithms performed similarly for quantitative analysis of 11 C-acetate cardiac PET imaging. TOF and TPSF yielded highly consistent kinetic parameter results with superior image quality compared with FBP. OSEM was relatively less reliable. Both TOF and TPSF were recommended for cardiac 11 C-acetate kinetic analysis.

Echocardiography and cardiac resynchronisation therapy, friends or foes?

PubMed

van Everdingen, W M; Schipper, J C; van 't Sant, J; Ramdat Misier, K; Meine, M; Cramer, M J

2016-01-01

Echocardiography is used in cardiac resynchronisation therapy (CRT) to assess cardiac function, and in particular left ventricular (LV) volumetric status, and prediction of response. Despite its widespread applicability, LV volumes determined by echocardiography have inherent measurement errors, interobserver and intraobserver variability, and discrepancies with the gold standard magnetic resonance imaging. Echocardiographic predictors of CRT response are based on mechanical dyssynchrony. However, parameters are mainly tested in single-centre studies or lack feasibility. Speckle tracking echocardiography can guide LV lead placement, improving volumetric response and clinical outcome by guiding lead positioning towards the latest contracting segment. Results on optimisation of CRT device settings using echocardiographic indices have so far been rather disappointing, as results suffer from noise. Defining response by echocardiography seems valid, although re-assessment after 6 months is advisable, as patients can show both continuous improvement as well as deterioration after the initial response. Three-dimensional echocardiography is interesting for future implications, as it can determine volume, dyssynchrony and viability in a single recording, although image quality needs to be adequate. Deformation patterns from the septum and the derived parameters are promising, although validation in a multicentre trial is required. We conclude that echocardiography has a pivotal role in CRT, although clinicians should know its shortcomings.

Renin-Angiotensin-Aldosterone Signaling Inhibitors-Losartan, Enalapril, and Cardosten-Prevent Infarction-induced Heart Failure Development in Rats.

PubMed

Kiss, Krisztina; Fekete, Veronika; Pálóczi, János; Sárközy, Márta; Murlasits, Zsolt; Pipis, Judit; Kheyfets, Irina A; Dugina, Julia L; Sergeeva, Svetlana A; Epstein, Oleg I; Csonka, Csaba; Csont, Tamás; Ferdinandy, Péter; Bencsik, Péter

2016-01-01

The activation of the renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of congestive heart failure, which is the reason that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin 2 receptor blockers (ARBs) have become established therapies for heart failure. However, it is still not known whether preventive treatment with losartan or enalapril can reduce symptoms of infarction-induced heart failure. Ultra-low dose (ULD) drug therapy is thought to exert specific activity, with a lower chance of side effects. OBJECTIVES • The research team had hypothesized that preventive treatment with inhibitors of RAAS signaling-losartan, enalapril, and a preparation of a ULD antibody (ie, cardosten), which target the angiotensin type 1 (AT1) receptor-might alleviate pathological hypertrophy and/or functional decline in infarction-induced heart failure. The research team treated male Wistar rats orally for 30 d with 20 mg/kg of losartan, 10 mg/kg enalapril, 5 or 7.5 mL/kg of cardosten, or a control solution, started 1 d prior to permanent coronary occlusion. A sham-operated group functioned as a second control group. The study was conducted at the Department of Biochemistry of the Faculty of Medicine at the University of Szeged in Szeged, Hungary, in cooperation with the Pharmahungary Group, also in Szeged, Hungary, and with OOO "NPF" Materia Medica Holding Ltd in Moscow, Russia. To determine cardiac functional parameters in vivo, the research team inserted a catheter into the left ventricle of the rats and measured the parameters of ventricular pressure, and cardiac output was determined by thermodilution. Morphological parameters were measured after heart isolation in transverse sections by a digital caliper. A total of 30 d after permanent coronary ligation, both losartan and enalapril, significantly decreased mean arterial blood pressure (MABP), attenuated the development of the left-ventricular anterior-wall and septum hypertrophy, and reduced scar thickness compared with the vehicle control group. The deterioration of cardiac output and the increase in total peripheral resistance (TPR) due to coronary ligation were significantly inhibited by both losartan and enalapril. The effects of cardosten were comparable with those of losartan and enalapril on cardiac morphology, left ventricular function, and TPR; however, it did not influence MABP. Moreover, in contrast to losartan and enalapril, cardosten did not decrease the rate of survival. The study was the first to have demonstrated that preventive treatment with losartan, enalapril, or cardosten can attenuate pathological hypertrophy in infarction-induced heart failure in rats.

Myocardial function during bradycardia events in preterm infants.

PubMed

de Waal, Koert; Phad, Nilkant; Collins, Nick; Boyle, Andrew

2016-07-01

Transient bradycardia episodes are common in preterm infants and often secondary to apnea. Decreased ventilation with resultant hypoxemia is believed to be the predominant mechanism. Sudden bradycardias without apnea are also reported, possibly due to vagal stimulation. Point of care ultrasound is used to diagnose and follow cardiovascular complications in preterm infants. Inadvertently, the operator would sometimes capture bradycardia events. This study reports on left ventricular function during such events. We retrospectively reviewed our cardiac ultrasound database for bradycardia events. Apical four or three chamber images before, during and after a bradycardia event were analysed with speckle tracking software which provides systolic and diastolic parameters of myocardial motion, deformation and volume. Over a 2year period, 15 bradycardia events were noted in 14 patients with a median gestational age of 26weeks (range 23 to 29). Heart rate decreased by an average of 43% (171/min to 98/min). Myocardial velocity and longitudinal strain rate during the atrial component of diastole were reduced during bradycardia. Longitudinal strain during systole was increased and radial deformation was unchanged. Ventricular volumes and ejection fraction did not change. Most parameters returned to baseline values after the event. Longitudinal systolic strain rate remained lower and stroke volume was 12% higher compared to baseline. Parameters of systolic contractility and stroke volume were maintained and parameters of atrial contractility were reduced during mild to moderate bradycardia in preterm infants. Bradycardia reduces total cardiac output with a compensatory increase detected following the event. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Outcome quality of in-patient cardiac rehabilitation in elderly patients--identification of relevant parameters.

PubMed

Salzwedel, Annett; Nosper, Manfred; Röhrig, Bernd; Linck-Eleftheriadis, Sigrid; Strandt, Gert; Völler, Heinz

2014-02-01

Outcome quality management requires the consecutive registration of defined variables. The aim was to identify relevant parameters in order to objectively assess the in-patient rehabilitation outcome. From February 2009 to June 2010 1253 patients (70.9 ± 7.0 years, 78.1% men) at 12 rehabilitation clinics were enrolled. Items concerning sociodemographic data, the impairment group (surgery, conservative/interventional treatment), cardiovascular risk factors, structural and functional parameters and subjective health were tested in respect of their measurability, sensitivity to change and their propensity to be influenced by rehabilitation. The majority of patients (61.1%) were referred for rehabilitation after cardiac surgery, 38.9% after conservative or interventional treatment for an acute coronary syndrome. Functionally relevant comorbidities were seen in 49.2% (diabetes mellitus, stroke, peripheral artery disease, chronic obstructive lung disease). In three key areas 13 parameters were identified as being sensitive to change and subject to modification by rehabilitation: cardiovascular risk factors (blood pressure, low-density lipoprotein cholesterol, triglycerides), exercise capacity (resting heart rate, maximal exercise capacity, maximal walking distance, heart failure, angina pectoris) and subjective health (IRES-24 (indicators of rehabilitation status): pain, somatic health, psychological well-being and depression as well as anxiety on the Hospital Anxiety and Depression Scale). The outcome of in-patient rehabilitation in elderly patients can be comprehensively assessed by the identification of appropriate key areas, that is, cardiovascular risk factors, exercise capacity and subjective health. This may well serve as a benchmark for internal and external quality management.

Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study

PubMed Central

Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

2017-01-01

It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension–Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes of Sleepiness–Wakefulness and Gloomy–Refreshed. This indicated that listening to music improved the participants' feelings of fatigue and decreased their heart rates. However, it did not reduce the cardiac LF/HF, suggesting that cardiac LF/HF might show a delayed response to fatigue. Thus, we demonstrated changes in cardiac autonomic nervous functions based on feelings of fatigue. PMID:28344545

Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study.

PubMed

Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-Ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

2017-01-01

It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension-Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes of Sleepiness-Wakefulness and Gloomy-Refreshed. This indicated that listening to music improved the participants' feelings of fatigue and decreased their heart rates. However, it did not reduce the cardiac LF/HF, suggesting that cardiac LF/HF might show a delayed response to fatigue. Thus, we demonstrated changes in cardiac autonomic nervous functions based on feelings of fatigue.

Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy.

PubMed

Sacre, J W; Jellis, C L; Coombes, J S; Marwick, T H

2012-09-01

Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P < 0.01). Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P < 0.05). Area under the receiver-operating characteristic curve revealed good diagnostic performance of all heart-rate recovery parameters (range 0.80-0.83, P < 0.001). Optimal cut-offs for heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P < 0.05). Post-exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Left atrial function in heart failure with impaired and preserved ejection fraction.

PubMed

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Spiral-Wave Dynamics in a Mathematical Model of Human Ventricular Tissue with Myocytes and Fibroblasts

PubMed Central

Nayak, Alok Ranjan; Shajahan, T. K.; Panfilov, A. V.; Pandit, Rahul

2013-01-01

Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as , the fibroblast resting-membrane potential, the fibroblast conductance , and the MF gap-junctional coupling . Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as , and , and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity decreases as a function of , for zero-sided and one-sided couplings; however, for two-sided coupling, decreases initially and then increases as a function of , and, eventually, we observe that conduction failure occurs for low values of . In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling or . Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities. PMID:24023798

Optimisation of reconstruction--reprojection-based motion correction for cardiac SPECT.

PubMed

Kangasmaa, Tuija S; Sohlberg, Antti O

2014-07-01

Cardiac motion is a challenging cause of image artefacts in myocardial perfusion SPECT. A wide range of motion correction methods have been developed over the years, and so far automatic algorithms based on the reconstruction--reprojection principle have proved to be the most effective. However, these methods have not been fully optimised in terms of their free parameters and implementational details. Two slightly different implementations of reconstruction--reprojection-based motion correction techniques were optimised for effective, good-quality motion correction and then compared with each other. The first of these methods (Method 1) was the traditional reconstruction-reprojection motion correction algorithm, where the motion correction is done in projection space, whereas the second algorithm (Method 2) performed motion correction in reconstruction space. The parameters that were optimised include the type of cost function (squared difference, normalised cross-correlation and mutual information) that was used to compare measured and reprojected projections, and the number of iterations needed. The methods were tested with motion-corrupt projection datasets, which were generated by adding three different types of motion (lateral shift, vertical shift and vertical creep) to motion-free cardiac perfusion SPECT studies. Method 2 performed slightly better overall than Method 1, but the difference between the two implementations was small. The execution time for Method 2 was much longer than for Method 1, which limits its clinical usefulness. The mutual information cost function gave clearly the best results for all three motion sets for both correction methods. Three iterations were sufficient for a good quality correction using Method 1. The traditional reconstruction--reprojection-based method with three update iterations and mutual information cost function is a good option for motion correction in clinical myocardial perfusion SPECT.

Temporal partitioning of adaptive responses of the murine heart to fasting.

PubMed

Brewer, Rachel A; Collins, Helen E; Berry, Ryan D; Brahma, Manoja K; Tirado, Brian A; Peliciari-Garcia, Rodrigo A; Stanley, Haley L; Wende, Adam R; Taegtmeyer, Heinrich; Rajasekaran, Namakkal Soorappan; Darley-Usmar, Victor; Zhang, Jianhua; Frank, Stuart J; Chatham, John C; Young, Martin E

2018-03-15

Recent studies suggest that the time of day at which food is consumed dramatically influences clinically-relevant cardiometabolic parameters (e.g., adiposity, insulin sensitivity, and cardiac function). Meal feeding benefits may be the result of daily periods of feeding and/or fasting, highlighting the need for improved understanding of the temporal adaptation of cardiometabolic tissues (e.g., heart) to fasting. Such studies may provide mechanistic insight regarding how time-of-day-dependent feeding/fasting cycles influence cardiac function. We hypothesized that fasting during the sleep period elicits beneficial adaptation of the heart at transcriptional, translational, and metabolic levels. To test this hypothesis, temporal adaptation was investigated in wild-type mice fasted for 24-h, or for either the 12-h light/sleep phase or the 12-h dark/awake phase. Fasting maximally induced fatty acid responsive genes (e.g., Pdk4) during the dark/active phase; transcriptional changes were mirrored at translational (e.g., PDK4) and metabolic flux (e.g., glucose/oleate oxidation) levels. Similarly, maximal repression of myocardial p-mTOR and protein synthesis rates occurred during the dark phase; both parameters remained elevated in the heart of fasted mice during the light phase. In contrast, markers of autophagy (e.g., LC3II) exhibited peak responses to fasting during the light phase. Collectively, these data show that responsiveness of the heart to fasting is temporally partitioned. Autophagy peaks during the light/sleep phase, while repression of glucose utilization and protein synthesis is maximized during the dark/active phase. We speculate that sleep phase fasting may benefit cardiac function through augmentation of protein/cellular constituent turnover. Copyright © 2018 Elsevier Inc. All rights reserved.

Cardiopulmonary reflex, cardiac cytokines, and nandrolone decanoate: response to resistance training in rats.

PubMed

Lima, Ewelyne Miranda; Nascimento, Andrews Marques; Brasil, Girlandia Alexandre; Kalil, Ieda Carneiro; Lenz, Dominik; Endringer, Denise Coutinho; Andrade, Tadeu Uggere; Bissoli, Nazaré Souza

2015-11-01

This study evaluated the effects of nandrolone associated with resistance training (RT) on cardiac cytokines, angiotensin-converting enzyme activity (ACEA), and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: CONT (received vehicle, no training); EXERC (RT: after one week of water adaptation, rats were exercised by jumping into water twice a week for 4 weeks), and ND+EXERC (received nandrolone decanoate 10 mg/kg, twice/week, i.m, associated with RT). The BJR was analysed by measuring bradycardic and hypotensive responses elicited by serotonin administration. Myocyte hypertrophy and matrix collagen deposition were determined by morphometric analysis of H&E and picrosirius red-stained samples, respectively. TNF-α and ACEA were also studied. RT promoted physiological myocyte hyrpertrophy but did not cause changes in the other parameters. The association of ND with RT increased myocyte hypertrophy, deposition of matrix type I collagen, TNF-α and ACEA; decreased IL-10, and impairment in the BJR were observed in ND+EXERC compared with CONT and EXERC. ND is associated with alterations in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cardiac cytokine imbalance, elevation of ACEA) and cardiac injury, even when combined with resistance training.

Dual chamber stent prevents organ malperfusion in a model of donation after cardiac death.

PubMed

Tillman, Bryan W; Chun, Youngjae; Cho, Sung Kwon; Chen, Yanfei; Liang, Nathan; Maul, Timothy; Demetris, Anthony; Gu, Xinzhu; Wagner, William R; Tevar, Amit D

2016-10-01

The paradigm for donation after cardiac death subjects donor organs to ischemic injury. A dual-chamber organ perfusion stent would maintain organ perfusion without affecting natural cardiac death. A center lumen allows uninterrupted cardiac blood flow, while an external chamber delivers oxygenated blood to the visceral vessels. A prototype organ perfusion stent was constructed from commercial stents. In a porcine model, the organ perfusion stent was deployed, followed by a simulated agonal period. Oxygenated blood perfused the external stent chamber. Organ perfusion was compared between controls (n = 3) and organ perfusion stent (n = 6). Finally, a custom, nitinol, dual chamber organ perfusion stent was fabricated using a retrievable "petal and stem" design. Endovascular organ perfusion stent deployment achieved visceral isolation without adverse impact on cardiac parameters. Visceral oxygen delivery was 4.8-fold greater compared with controls. During the agonal period, organs in organ perfusion stent-treated animals appeared well perfused in contrast with the malperfused controls. A custom nitinol and polyurethane organ perfusion stent was recaptured easily with simple sheath advancement. An organ perfusion stent maintained organ perfusion during the agonal phase in a porcine model of donation after cardiac death organ donation without adversely affecting cardiac function. Ultimately, the custom retrievable design of this study may help resolve the critical shortage of donor organs for transplant. Copyright © 2016 Elsevier Inc. All rights reserved.

Echocardiographic parameters of captive western lowland gorillas (Gorilla gorilla gorilla).

PubMed

Murphy, Hayley Weston; Dennis, Patricia; Devlin, William; Meehan, Tom; Kutinsky, Ilana

2011-12-01

A total of 163 echocardiographic studies on western lowland gorillas (Gorilla gorilla gorilla) were submitted for evaluation; 140 from 99 animals were suitable for analysis. Of these, 81 studies (42 studies from 35 males ranging in age from 11-41+ yr and 39 studies from 31 females ranging in age from 11-41+ yr) are reported here. Three studies from 3 females and 56 studies from 30 males were excluded from this report due to cardiac abnormalities. Cardiac parameters measured were aortic root (Ao Rt) diameter and left atrial (L atrium) size. Left ventricular (LV) measurements included left ventricular internal diameter in systole (LVID(s)) and diastole (LVID(d)) as well as diastolic septal (IVS) and posterior wall thickness (LVPW). Values considered to be normal in females > 11 yr of age were: Ao Rt < 3.5 cm, L atrium < 4.0 cm, LVID(d) < 5.0 cm, IVS < 1.4 cm, LVPW < 1.4 cm, and ejection fraction (EF) > 60%. The data from male gorillas show a separation in animals based on three cardiac parameters: systolic function, LV cavity size, and LV wall thickness. Male gorillas > 11 yr of age fall into two groups; unaffected and affected. Unaffected animals are defined as those with no echocardiographic abnormalities and a consistent Ao Rt of < 4.0 cm, LVID(d) of < 6.0 cm, IVS and LVPW of <1.5 cm, and an EF of > 58%. The affected group consisted of male gorillas that exhibited changes in echocardiographic parameters representing the presence of cardiovascular disease. The results determined in this database, gathered from data collected from 1999-2009, suggest a sex-based difference between males and females with predominantly males demonstrating evidence of cardiac disease. The most striking finding seen in this study is that of progressive LV hypertrophy and depressed LV EF in affected adult male gorillas.

Cardiac output by pulse contour analysis does not match the increase measured by rebreathing during human spaceflight.

PubMed

Hughson, Richard L; Peterson, Sean D; Yee, Nicholas J; Greaves, Danielle K

2017-11-01

Pulse contour analysis of the noninvasive finger arterial pressure waveform provides a convenient means to estimate cardiac output (Q̇). The method has been compared with standard methods under a range of conditions but never before during spaceflight. We compared pulse contour analysis with the Modelflow algorithm to estimates of Q̇ obtained by rebreathing during preflight baseline testing and during the final month of long-duration spaceflight in nine healthy male astronauts. By Modelflow analysis, stroke volume was greater in supine baseline than seated baseline or inflight. Heart rate was reduced in supine baseline so that there were no differences in Q̇ by Modelflow estimate between the supine (7.02 ± 1.31 l/min, means ± SD), seated (6.60 ± 1.95 l/min), or inflight (5.91 ± 1.15 l/min) conditions. In contrast, rebreathing estimates of Q̇ increased from seated baseline (4.76 ± 0.67 l/min) to inflight (7.00 ± 1.39 l/min, significant interaction effect of method and spaceflight, P < 0.001). Pulse contour analysis utilizes a three-element Windkessel model that incorporates parameters dependent on aortic pressure-area relationships that are assumed to represent the entire circulation. We propose that a large increase in vascular compliance in the splanchnic circulation invalidates the model under conditions of spaceflight. Future spaceflight research measuring cardiac function needs to consider this important limitation for assessing absolute values of Q̇ and stroke volume. NEW & NOTEWORTHY Noninvasive assessment of cardiac function during human spaceflight is an important tool to monitor astronaut health. This study demonstrated that pulse contour analysis of finger arterial blood pressure to estimate cardiac output failed to track the 46% increase measured by a rebreathing method. These results strongly suggest that alternative methods not dependent on pulse contour analysis are required to track cardiac function in spaceflight. Copyright © 2017 the American Physiological Society.

Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse.

PubMed

Gómez-Hurtado, Nieves; Domínguez-Rodríguez, Alejandro; Mateo, Philippe; Fernández-Velasco, María; Val-Blasco, Almudena; Aizpún, Rafael; Sabourin, Jessica; Gómez, Ana María; Benitah, Jean-Pierre; Delgado, Carmen

2017-07-01

Leptin, is a 16 kDa pleiotropic peptide not only primarily secreted by adipocytes, but also produced by other tissues, including the heart. Controversy exists regarding the adverse and beneficial effects of leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction. We find that leptin activates mechanisms that contribute to cardiac dysfunction under physiological conditions. However, after the establishment of pressure overload, an increase in leptin levels has protective cardiac effects with respect to rescuing the cellular heart failure phenotype. These beneficial effects of leptin involve restoration of action potential duration via normalization of transient outward potassium current and sarcoplasmic reticulum Ca 2+ content via rescue of control sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase levels and ryanodine receptor function modulation, leading to normalization of Ca 2+ handling parameters. Leptin, is a 16 kDa pleiotropic peptide not only primary secreted by adipocytes, but also produced by other tissues, including the heart. Evidence indicates that leptin may have either adverse or beneficial effects on the heart. To obtain further insights, in the present study, we analysed the effect of leptin treatment on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction (TAC). Three weeks after surgery, animals received either leptin (0.36 mg kg -1  day -1 ) or vehicle via osmotic minipumps for 3 weeks. Echocardiographic measurements showed that, although leptin treatment was deleterious on cardiac function in sham, leptin had a cardioprotective effect following TAC. [Ca 2+ ] i transient in cardiomyocytes followed similar pattern. Patch clamp experiments showed prolongation of action potential duration (APD) in TAC and leptin-treated sham animals, whereas, following TAC, leptin reduced the APD towards control values. APD variations were associated with decreased transient outward potassium current and Kv4.2 and KChIP2 protein expression. TAC myocytes showed a higher incidence of triggered activities and spontaneous Ca 2+ waves. These proarrhythmic manifestations, related to Ca 2+ /calmodulin-dependent protein kinase II and ryanodine receptor phosphorylation, were reduced by leptin. The results of the present study demonstrate that, although leptin treatment was deleterious on cardiac function in control animals, leptin had a cardioprotective effect following TAC, normalizing cardiac function and reducing arrhythmogeneity at the cellular level. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

[Effectiveness of various dopamine doses in acute myocardial ischemia complicated by cardiogenic shock (an experimental study)].

PubMed

Kipshidze, N N; Korotkov, A A; Marsagishvili, L A; Prigolashvili, T Sh; Bokhua, M R

1981-06-01

The effect of various doses of dopamine on the values of cardiac contractile and hemodynamic function under conditions of acute two-hour ischemia complicated by cardiogenic shock was studied in 27 experiments on dogs. In a dose of 5 microgram/kg/min dopamine caused an optimum increase in cardiac productive capacity, reduction of peripheral resistance, adequate increase in coronary circulation and decrease in ST segment depression on the ECG. Infusion of 10 microgram/kg/min dopamine usually caused myocardial hyperfunction with an increase in total peripheral resistance and cardiac performance. Maximum dopamine doses (10 microgram/kg/min and more) were effective in the areactive form of cardiogenic shock. In longterm dopamine infusion it is necessary to establish continuous control over the hemodynamic parameters and the ECG to prevent aggravation of ischemia and for stage-by-stage reduction of the drug concentration and determination of the minimum maintenance dose.

Cardio-Metabolic Effects of HIV Protease Inhibitors (Lopinavir/Ritonavir)

PubMed Central

Reyskens, Kathleen M. S. E.; Fisher, Tarryn-Lee; Schisler, Jonathan C.; O'Connor, Wendi G.; Rogers, Arlin B.; Willis, Monte S.; Planesse, Cynthia; Boyer, Florence; Rondeau, Philippe; Bourdon, Emmanuel; Essop, M. Faadiel

2013-01-01

Although antiretroviral treatment decreases HIV-AIDS morbidity/mortality, long-term side effects may include the onset of insulin resistance and cardiovascular diseases. However, the underlying molecular mechanisms responsible for highly active antiretroviral therapy (HAART)-induced cardio-metabolic effects are poorly understood. In light of this, we hypothesized that HIV protease inhibitor (PI) treatment (Lopinavir/Ritonavir) elevates myocardial oxidative stress and concomitantly inhibits the ubiquitin proteasome system (UPS), thereby attenuating cardiac function. Lopinavir/Ritonavir was dissolved in 1% ethanol (vehicle) and injected into mini-osmotic pumps that were surgically implanted into Wistar rats for 8 weeks vs. vehicle and sham controls. We subsequently evaluated metabolic parameters, gene/protein markers and heart function (ex vivo Langendorff perfusions). PI-treated rats exhibited increased serum LDL-cholesterol, higher tissue triglycerides (heart, liver), but no evidence of insulin resistance. In parallel, there was upregulation of hepatic gene expression, i.e. acetyl-CoA carboxylase β and 3-hydroxy-3-methylglutaryl-CoA-reductase, key regulators of fatty acid oxidation and cholesterol synthesis, respectively. PI-treated hearts displayed impaired cardiac contractile function together with attenuated UPS activity. However, there was no significant remodeling of hearts exposed to PIs, i.e. lack of ultrastructural changes, fibrosis, cardiac hypertrophic response, and oxidative stress. Western blot analysis of PI-treated hearts revealed that perturbed calcium handling may contribute to the PI-mediated contractile dysfunction. Here chronic PI administration led to elevated myocardial calcineurin, nuclear factor of activated T-cells 3 (NFAT3), connexin 43, and phosphorylated phospholamban, together with decreased calmodulin expression levels. This study demonstrates that early changes triggered by PI treatment include increased serum LDL-cholesterol levels together with attenuated cardiac function. Furthermore, PI exposure inhibits the myocardial UPS and leads to elevated calcineurin and connexin 43 expression that may be associated with the future onset of cardiac contractile dysfunction. PMID:24098634

Endocardial left ventricle feature tracking and reconstruction from tri-plane trans-esophageal echocardiography data

NASA Astrophysics Data System (ADS)

Dangi, Shusil; Ben-Zikri, Yehuda K.; Cahill, Nathan; Schwarz, Karl Q.; Linte, Cristian A.

2015-03-01

Two-dimensional (2D) ultrasound (US) has been the clinical standard for over two decades for monitoring and assessing cardiac function and providing support via intra-operative visualization and guidance for minimally invasive cardiac interventions. Developments in three-dimensional (3D) image acquisition and transducer design and technology have revolutionized echocardiography imaging enabling both real-time 3D trans-esophageal and intra-cardiac image acquisition. However, in most cases the clinicians do not access the entire 3D image volume when analyzing the data, rather they focus on several key views that render the cardiac anatomy of interest during the US imaging exam. This approach enables image acquisition at a much higher spatial and temporal resolution. Two such common approaches are the bi-plane and tri-plane data acquisition protocols; as their name states, the former comprises two orthogonal image views, while the latter depicts the cardiac anatomy based on three co-axially intersecting views spaced at 600 to one another. Since cardiac anatomy is continuously changing, the intra-operative anatomy depicted using real-time US imaging also needs to be updated by tracking the key features of interest and endocardial left ventricle (LV) boundaries. Therefore, rapid automatic feature tracking in US images is critical for three reasons: 1) to perform cardiac function assessment; 2) to identify location of surgical targets for accurate tool to target navigation and on-target instrument positioning; and 3) to enable pre- to intra-op image registration as a means to fuse pre-op CT or MR images used during planning with intra-operative images for enhanced guidance. In this paper we utilize monogenic filtering, graph-cut based segmentation and robust spline smoothing in a combined work flow to process the acquired tri-plane TEE time series US images and demonstrate robust and accurate tracking of the LV endocardial features. We reconstruct the endocardial LV geometry using the tri-plane contours and spline interpolation, and assess the accuracy of the proposed work flow against gold-standard results from the GE Echopac PC clinical software according to quantitative clinical LV characterization parameters, such as the length, circumference, area and volume. Our proposed combined work flow leads to consistent, rapid and automated identification of the LV endocardium, suitable for intra-operative applications and "on-the-fly" computer-assisted assessment of ejection fraction for cardiac function monitoring.Two-dimensional (2D) ultrasound (US) has been the clinical standard for over two decades for monitoring and assessing cardiac function and providing support via intra-operative visualization and guidance for minimally invasive cardiac interventions. Developments in three-dimensional (3D) image acquisition and transducer design and technology have revolutionized echocardiography imaging enabling both real-time 3D trans-esophageal and intra-cardiac image acquisition. However, in most cases the clinicians do not access the entire 3D image volume when analyzing the data, rather they focus on several key views that render the cardiac anatomy of interest during the US imaging exam. This approach enables image acquisition at a much higher spatial and temporal resolution. Two such common approaches are the bi-plane and tri-plane data acquisition protocols; as their name states, the former comprises two orthogonal image views, while the latter depicts the cardiac anatomy based on three co-axially intersecting views spaced at 600 to one another. Since cardiac anatomy is continuously changing, the intra-operative anatomy depicted using real-time US imaging also needs to be updated by tracking the key features of interest and endocardial left ventricle (LV) boundaries. Therefore, rapid automatic feature tracking in US images is critical for three reasons: 1) to perform cardiac function assessment; 2) to identify location of surgical targets for accurate tool to target navigation and on-target instrument positioning; and 3) to enable pre- to intra-op image registration as a means to fuse pre-op CT or MR images used during planning with intra-operative images for enhanced guidance. In this paper we utilize monogenic filtering, graph-cut based segmentation and robust spline smoothing in a combined work flow to process the acquired tri-plane TEE time series US images and demonstrate robust and accurate tracking of the LV endocardial features. We reconstruct the endocardial LV geometry using the tri-plane contours and spline interpolation, and assess the accuracy of the proposed work flow against gold-standard results from the GE Echopac PC clinical software according to quantitative clinical LV characterization parameters, such as the length, circumference, area and volume. Our proposed combined work flow leads to consistent, rapid and automated identification of the LV endocardium, suitable for intra-operative applications and on-the- y" computer-assisted assessment of ejection fraction for cardiac function monitoring.

Neonatal autonomic function after pregnancy complications and early cardiovascular development.

PubMed

Aye, Christina Y L; Lewandowski, Adam James; Oster, Julien; Upton, Ross; Davis, Esther; Kenworthy, Yvonne; Boardman, Henry; Yu, Grace Z; Siepmann, Timo; Adwani, Satish; McCormick, Kenny; Sverrisdottir, Yrsa B; Leeson, Paul

2018-05-23

Heart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period. Ninety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age. Increasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p < 0.001, p = 0.009 and p = 0.007, respectively). We also demonstrated a relative imbalance between sympathetic and parasympathetic tone, compared to the term infants. However, differences in autonomic function did not predict cardiovascular measures at either time point. Altered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.

Misalignment with the external light environment drives metabolic and cardiac dysfunction.

PubMed

West, Alexander C; Smith, Laura; Ray, David W; Loudon, Andrew S I; Brown, Timothy M; Bechtold, David A

2017-09-12

Most organisms use internal biological clocks to match behavioural and physiological processes to specific phases of the day-night cycle. Central to this is the synchronisation of internal processes across multiple organ systems. Environmental desynchrony (e.g. shift work) profoundly impacts human health, increasing cardiovascular disease and diabetes risk, yet the underlying mechanisms remain unclear. Here, we characterise the impact of desynchrony between the internal clock and the external light-dark (LD) cycle on mammalian physiology. We reveal that even under stable LD environments, phase misalignment has a profound effect, with decreased metabolic efficiency and disrupted cardiac function including prolonged QT interval duration. Importantly, physiological dysfunction is not driven by disrupted core clock function, nor by an internal desynchrony between organs, but rather the altered phase relationship between the internal clockwork and the external environment. We suggest phase misalignment as a major driver of pathologies associated with shift work, chronotype and social jetlag.The misalignment between internal circadian rhythm and the day-night cycle can be caused by genetic, behavioural and environmental factors, and may have a profound impact on human physiology. Here West et al. show that desynchrony between the internal clock and the external environment alter metabolic parameters and cardiac function in mice.

Heart repair by reprogramming non-myocytes with cardiac transcription factors

PubMed Central

Song, Kunhua; Nam, Young-Jae; Luo, Xiang; Qi, Xiaoxia; Tan, Wei; Huang, Guo N.; Acharya, Asha; Smith, Christopher L.; Tallquist, Michelle D.; Neilson, Eric G.; Hill, Joseph A.; Bassel-Duby, Rhonda; Olson, Eric N.

2012-01-01

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodeling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, Hand2, MEF2C and Tbx5 can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodeling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules. PMID:22660318

Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction

PubMed Central

Chung, Ha-Yeun; Kollmey, Anna S.; Schrepper, Andrea; Kohl, Matthias; Bläss, Markus F.; Stehr, Sebastian N.; Lupp, Amelie; Gräler, Markus H.; Claus, Ralf A.

2017-01-01

Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients’ mortality. Acid sphingomyelinase (SMPD1)—the principal regulator for rapid and transient generation of the lipid mediator ceramide—is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1+/+ as well as SMPD1−/− animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1−/− littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine. PMID:28420138

Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction.

PubMed

Chung, Ha-Yeun; Kollmey, Anna S; Schrepper, Andrea; Kohl, Matthias; Bläss, Markus F; Stehr, Sebastian N; Lupp, Amelie; Gräler, Markus H; Claus, Ralf A

2017-04-15

Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients' mortality. Acid sphingomyelinase (SMPD1)-the principal regulator for rapid and transient generation of the lipid mediator ceramide-is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1 +/+ as well as SMPD1 -/- animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1 -/- littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine.

Cardiac systolic dysfunction in doxorubicin-challenged rats is associated with upregulation of MuRF2 and MuRF3 E3 ligases

PubMed Central

da Silva, Marcia Gracindo; Mattos, Elisabete; Camacho-Pereira, Juliana; Domitrovic, Tatiana; Galina, Antonio; Costa, Mauro W; Kurtenbach, Eleonora

2012-01-01

Doxorubicin (DOXO) is an efficient and low-cost chemotherapeutic agent. The use of DOXO is limited by its side effects, including cardiotoxicity, that may progress to cardiac failure as a result of multifactorial events that have not yet been fully elucidated. In the present study, the effects of DOXO at two different doses were analyzed to identify early functional and molecular markers of cardiac distress. One group of rats received 7.5 mg/kg of DOXO (low-dose group) and was followed for 20 weeks. A subset of these animals was then subjected to an additional cycle of DOXO treatment, generating a cumulative dose of 20 mg/kg (high-dose group). Physiological and biochemical parameters were assessed in both treatment groups and in a control group that received saline. Systolic dysfunction was observed only in the high-dose group. Mitochondrial function analysis showed a clear reduction in oxidative cellular respiration for animals in both DOXO treatment groups, with evidence of complex I damage being observed. Transcriptional analysis by quantitative polymerase chain reaction revealed an increase in atrial natriuretic peptide transcript in the high-dose group, which is consistent with cardiac failure. Analysis of transcription levels of key components of the cardiac ubiquitin-proteasome system found that the ubiquitin E3 ligase muscle ring finger 1 (MuRF1) was upregulated in both the low- and high-dose DOXO groups. MuRF2 and MuRF3 were also upregulated in the high-dose group but not in the low-dose group. This molecular profile may be useful as an early physiological and energetic cardiac failure indicator for testing therapeutic interventions in animal models. PMID:23620696

Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers.

PubMed

Lipshultz, Steven E; Williams, Paige L; Zeldow, Bret; Wilkinson, James D; Rich, Kenneth C; van Dyke, Russell B; Seage, George R; Dooley, Laurie B; Kaltman, Jonathan R; Siberry, George K; Mofenson, Lynne M; Shearer, William T; Colan, Steven D

2015-01-02

We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children. We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs. There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores. There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations.

The role of a structured exercise training program on cardiac structure and function after acute myocardial infarction: study protocol for a randomized controlled trial.

PubMed

Fontes-Carvalho, Ricardo; Sampaio, Francisco; Teixeira, Madalena; Gama, Vasco; Leite-Moreira, Adelino F

2015-03-12

Exercise training is effective in improving functional capacity and quality of life in patients with coronary artery disease, but its effects on left ventricular systolic and diastolic function are controversial. Diastolic dysfunction is a major determinant of adverse outcome after myocardial infarction and, contrary to systolic function, no therapy or intervention has proved to significantly improve diastolic function. Data from animal studies and from patients with diastolic heart failure has suggested that exercise training can have a positive effect on diastolic function parameters. This trial aims to evaluate if a structured exercise training program can improve resting left ventricular diastolic and systolic function in patients who have had an acute myocardial infarction. This is a phase II, prospective, randomized, open-label, blinded-endpoint trial that will include at least 96 consecutive patients who have had an acute myocardial infarction one month previously. Patients will be randomized (1:1) to an exercise training program or a control group, receiving standard of care. At enrolment, and at the end of the follow-up period, patients will be submitted to an echocardiography (with detailed assessment of diastolic and systolic function using recent consensus guidelines), cardiopulmonary exercise testing, an anthropometric assessment, blood testing, and clinical evaluation. Patients randomized to the intervention group will be submitted to an eight-week outpatient exercise program, combining endurance and resistance training, for three sessions per week. The primary endpoint will be the change in lateral E' velocity immediately after the eight-week exercise training program. Secondary endpoints will include other echocardiographic parameters of left ventricular diastolic and systolic function, cardiac structure, metabolic and inflammation biomarkers (high-sensitivity C-reactive protein and pro-BNP), functional capacity (peak oxygen consumption and anaerobic threshold) and anthropometric measurements. New strategies that can improve left ventricular diastolic function are clinically needed. This will be the first trial to evaluate, in patients who have had an acute myocardial infarction, the effects of a structured program of exercise training on diastolic and systolic function, assessed by novel echocardiographic parameters. Registered with ClinicalTrials.gov (reference: NCT02224495 ) on 21 August 2014.

Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up.

PubMed

Berg, Jan; Kottwitz, Jan; Baltensperger, Nora; Kissel, Christine K; Lovrinovic, Marina; Mehra, Tarun; Scherff, Frank; Schmied, Christian; Templin, Christian; Lüscher, Thomas F; Heidecker, Bettina; Manka, Robert

2017-11-01

There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months. LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes. This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis. © 2017 American Heart Association, Inc.

Viscoelastic blood coagulation measurement with Sonoclot predicts postoperative bleeding in cardiac surgery after heparin reversal.

PubMed

Bischof, Dominique B; Ganter, Michael T; Shore-Lesserson, Linda; Hartnack, Sonja; Klaghofer, Richard; Graves, Kirk; Genoni, Michele; Hofer, Christoph K

2015-01-01

The aim of the study was to determine if Sonoclot with its sensitive glass bead-activated, viscoelastic test can predict postoperative bleeding in patients undergoing cardiac surgery at predefined time points. A prospective, observational clinical study. A teaching hospital, single center. Consecutive patients undergoing cardiac surgery (N = 300). Besides routine laboratory coagulation studies and heparin management with standard (kaolin) activated clotting time, additional native blood samples were analyzed on a Sonoclot using glass bead-activated tests. Glass bead-activated clotting time, clot rate, and platelet function were recorded immediately before anesthesia induction and at the end of surgery after heparin reversal but before chest closure. Primary outcome was postoperative blood loss (chest tube drainage at 4, 8, and 12 hours postoperatively). Secondary outcome parameters were transfusion requirements, need for surgical re-exploration, time of mechanical ventilation, length of intensive care unit and hospital stay, and hospital morbidity and mortality. Patients were categorized into "bleeders" and "nonbleeders." Patient characteristics, operations, preoperative standard laboratory parameters, and procedural times were comparable between bleeders and nonbleeders except for sex and age. Bleeders had higher rates of transfusions, surgical re-explorations, and complications. Only glass bead measurements by Sonoclot after heparin reversal before chest closure but not preoperatively were predictive for increased postoperative bleeding. Sonoclot with its glass bead-activated tests may predict the risk for postoperative bleeding in patients undergoing cardiac surgery at the end of surgery after heparin reversal but before chest closure. Copyright © 2015 Elsevier Inc. All rights reserved.

Empowering human cardiac progenitor cells by P2Y14 nucleotide receptor overexpression.

PubMed

Khalafalla, Farid G; Kayani, Waqas; Kassab, Arwa; Ilves, Kelli; Monsanto, Megan M; Alvarez, Roberto; Chavarria, Monica; Norman, Benjamin; Dembitsky, Walter P; Sussman, Mark A

2017-12-01

Autologous cardiac progenitor cell (CPC) therapy is a promising approach for treatment of heart failure (HF). There is an unmet need to identify inherent deficits in aged/diseased human CPCs (hCPCs) derived from HF patients in the attempts to augment their regenerative capacity prior to use in the clinical setting. Here we report significant functional correlations between phenotypic properties of hCPCs isolated from cardiac biopsies of HF patients, clinical parameters of patients and expression of the P2Y 14 purinergic receptor (P2Y 14 R), a crucial detector for extracellular UDP-sugars released during injury/stress. P2Y 14 R is downregulated in hCPCs derived from HF patients with lower ejection fraction or diagnosed with diabetes. Augmenting P2Y 14 R expression levels in aged/diseased hCPCs antagonizes senescence and improves functional responses. This study introduces purinergic signalling modulation as a potential strategy to rejuvenate and improve phenotypic characteristics of aged/functionally compromised hCPCs prior to transplantation in HF patients. Autologous cardiac progenitor cell therapy is a promising alternative approach to current inefficient therapies for heart failure (HF). However, ex vivo expansion and pharmacological/genetic modification of human cardiac progenitor cells (hCPCs) are necessary interventions to rejuvenate aged/diseased cells and improve their regenerative capacities. This study was designed to assess the potential of improving hCPC functional capacity by targeting the P2Y 14 purinergic receptor (P2Y 14 R), which has been previously reported to induce regenerative and anti-senescence responses in a variety of experimental models. c-Kit + hCPCs were isolated from cardiac biopsies of multiple HF patients undergoing left ventricular assist device implantation surgery. Significant correlations existed between the expression of P2Y 14 R in hCPCs and clinical parameters of HF patients. P2Y 14 R was downregulated in hCPCs derived from patients with a relatively lower ejection fraction and patients diagnosed with diabetes. hCPC lines with lower P2Y 14 R expression did not respond to P2Y 14 R agonist UDP-glucose (UDP-Glu) while hCPCs with higher P2Y 14 R expression showed enhanced proliferation in response to UDP-Glu stimulation. Mechanistically, UDP-Glu stimulation enhanced the activation of canonical growth signalling pathways ERK1/2 and AKT. Restoring P2Y 14 R expression levels in functionally compromised hCPCs via lentiviral-mediated overexpression improved proliferation, migration and survival under stress stimuli. Additionally, P2Y 14 R overexpression reversed senescence-associated morphology and reduced levels of molecular markers of senescence p16 INK4a , p53, p21 and mitochondrial reactive oxygen species. Findings from this study unveil novel biological roles of the UDP-sugar receptor P2Y 14 in hCPCs and suggest purinergic signalling modulation as a promising strategy to improve phenotypic properties of functionally impaired hCPCs. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Long-term echocardiographic and cardioscintigraphic effects of growth hormone treatment in adults with Prader-Willi syndrome.

PubMed

Marzullo, Paolo; Marcassa, Claudio; Minocci, Alessandro; Campini, Riccardo; Eleuteri, Ermanno; Gondoni, Luca Alessandro; Aimaretti, Gianluca; Sartorio, Alessandro; Scacchi, Massimo; Grugni, Graziano

2015-05-01

In Prader-Willi syndrome (PWS), an altered GH secretion has been related to reduced cardiac mass and systolic function compared to controls. The objective was to evaluate the cardiovascular response to a 4-year GH therapy in adult PWS patients. Study participants were nine severely obese PWS adults (three females, six males) and 13 age-, gender-, and body mass index-matched obese controls. In an open-label prospective study, assessment of endocrine parameters and metabolic outcome, whole-body and abdominal fat scans, echocardiography, and radionuclide angiography in unstimulated and dobutamine-stimulated conditions were conducted at baseline and after 1 and 4 years of GH treatment. GH treatment increased IGF-1 (P < .0001), decreased C-reactive protein levels (P < .05), improved visceral fat mass (P < .05), and achieved near-significant changes of fat and fat-free body mass in PWS patients. Left ventricle mass indexed by fat mass increased significantly after 1 and 4 years of GH therapy (P < .05) without evident abnormalities of diastolic function, while a trend toward a reduction of the ejection fraction was documented by echocardiography (P = .054). Radionuclide angiography revealed stable values throughout the study of both the left and right ventricle ejection fractions, although this was accompanied by a statistically nonsignificant reduction of the left ventricle filling rate. A positive association between lean body mass and left ventricle ejection fraction was evident during the study (P < .05). GH therapy increased the cardiac mass of PWS adults without causing overt abnormalities of systolic and diastolic function. Although the association between lean mass and left ventricle ejection fraction during GH therapy corroborates a favorable systemic outcome of long-term GH treatment in adults with PWS, subtle longitudinal modifications of functional parameters advocate appropriate cardiac monitoring in the long-term therapeutic strategy for PWS.

Long term effects of fetal undernutrition on rat heart. Role of hypertension and oxidative stress

PubMed Central

Rodríguez-Rodríguez, Pilar; López de Pablo, Angel L.; García-Prieto, Concha F.; Somoza, Beatriz; Quintana-Villamandos, Begoña; Gómez de Diego, José J.; Gutierrez-Arzapalo, Perla Y.; Ramiro-Cortijo, David; González, M. Carmen

2017-01-01

Background and aims Fetal undernutrition is a risk factor for heart disease in both genders, despite the protection of women against hypertension development. Using a rat model of maternal undernutrition (MUN) we aimed to assess possible sex differences in the development of cardiac alterations and the implication of hypertension and cardiac oxidative stress. Methods Male and female offspring from rats fed ad libitum (control) or with 50% of the normal daily intake during the second half of gestation (MUN) were used. Heart weight/body weight ratio (HW/BW), hemodynamic parameters (anaesthetized rats) and plasma brain natriuretic peptide (BNP, ELISA) were assessed in 21-day, 6-month and 22-month old rats. Plasma testosterone (ELISA) and cardiac protein expression of enzymes related to reactive oxygen species synthesis (p22phox, xanthine-oxidase) and degradation (catalase, Cu/Zn-SOD, Mn-SOD, Ec-SOD) were evaluated in 21-day and 6-month old rats (Western Blot). Heart structure and function was studied at the age of 22 months (echocardiography). Results At the age of 21 days MUN males exhibited significantly larger HW/BW and cardiac p22phox expression while females had reduced p22phox expression, compared to their respective sex-matched controls. At the age of 6-months, MUN males showed significantly larger blood pressure and cardiac xanthine-oxidase expression; MUN females were normotensive and had a lower cardiac expression of antioxidant enzymes, compared to their respective sex-matched controls. At the age of 22 months, both MUN males and females showed larger HW/BW and left ventricular mass and lower ejection fraction compared to sex-matched controls; only MUN males exhibited hypertension and a larger plasma BNP compared to aged male controls. Conclusions 1) During perinatal life females exposed to fetal undernutrition are protected from cardiac alterations, but in ageing they exhibit ventricular hypertrophy and functional loss, like MUN males; 2) cardiac oxidative stress might be implicated in the observed heart alterations in both sexes and 3) the severity of cardiac damage might be greater in males due to hypertension. PMID:28212445

Translational science approach for assessment of cardiovascular effects and proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron.

PubMed

Korstanje, Cees; Suzuki, Masanori; Yuno, Koichiro; Sato, Shuichi; Ukai, Masashi; Schneidkraut, Marlowe J; Yan, Gan X

2017-09-01

Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron. Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (I Kr , I Ks , I to , I Na , and I Ca,L ), on QT-interval, subendocardial APD 90 , T peak-end interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QT c ) in conscious dogs. In conscious dogs, mirabegron (0.01-10mg/kg, p.o.) dose-dependently increased HR, reduced SBP but DBP was unchanged. Propranolol blocked the decrease in SBP and attenuated HR increase at 100mg/kg mirabegron. Mirabegron, at 30, 60, or 100mg/kg, p.o., had no significant effect on the QT c interval. In paced dog ventricular wedge, neither mirabegron nor metabolites M5, M11, M12, M14, and M16 prolonged QT, altered transmural dispersion of repolarization, induced premature ventricular contractions, or induced ventricular tachycardia. Mirabegron nor its metabolites inhibited I Kr , I Ks , I to I Na , or I Ca,L at clinically relevant concentrations. Up to exposure levels well exceeding human clinical exposure no discernible effects on ion channel conductance or on arrhythmogenic parameters in ventricular wedge resulted for mirabegron, or its main metabolites, confirming human cardiac safety findings. In vivo, dose-related increases in HR with effects markedly higher than seen clinically, was mediated in part by cross-activation of beta-1 adrenoceptors. This non-clinical cardiac safety test program therefore proved predictive for human cardiac safety for mirabegron. Copyright © 2017. Published by Elsevier Inc.

Xenon for the prevention of postoperative delirium in cardiac surgery: study protocol for a randomized controlled clinical trial.

PubMed

Al Tmimi, Layth; Van de Velde, Marc; Herijgers, Paul; Meyns, Bart; Meyfroidt, Geert; Milisen, Koen; Fieuws, Steffen; Coburn, Mark; Poesen, Koen; Rex, Steffen

2015-10-09

Postoperative delirium (POD) is a manifestation of acute postoperative brain dysfunction that is frequently observed after cardiac surgery. POD is associated with short-term complications such as an increase in mortality, morbidity, costs and length of stay, but can also have long-term sequelae, including persistent cognitive deficits, loss of independence, and increased mortality for up to 2 years. The noble gas xenon has been demonstrated in various models of neuronal injury to exhibit remarkable neuroprotective properties. We therefore hypothesize that xenon anesthesia reduces the incidence of POD in elderly patients undergoing cardiac surgery with the use of cardiopulmonary bypass. One hundred and ninety patients, older than 65 years, and scheduled for elective cardiac surgery, will be enrolled in this prospective, randomized, controlled trial. Patients will be randomized to receive general anesthesia with either xenon or sevoflurane. Primary outcome parameter will be the incidence of POD in the first 5 postoperative days. The occurrence of POD will be assessed by trained research personnel, blinded to study group, with the validated 3-minute Diagnostic Confusion Assessment Method (3D-CAM) (on the intensive care unit in its version specifically adapted for the ICU), in addition to chart review and the results of delirium screening tools that will be performed by the bedside nurses). Secondary outcome parameters include duration and severity of POD, and postoperative cognitive function as assessed with the Mini-Mental State Examination. Older patients undergoing cardiac surgery are at particular risk to develop POD. Xenon provides remarkable hemodynamic stability and has been suggested in preclinical studies to exhibit neuroprotective properties. The present trial will assess whether the promising profile of xenon can be translated into a better outcome in the geriatric population. EudraCT Identifier: 2014-005370-11 (13 May 2015).

State of the Art: Clinical Applications of Cardiac T1 Mapping.

PubMed

Schelbert, Erik B; Messroghli, Daniel R

2016-03-01

While cardiovascular magnetic resonance (MR) has become the noninvasive tool of choice for the assessment of myocardial viability and for the detection of acute myocardial edema, cardiac T1 mapping is believed to further extend the ability of cardiovascular MR to characterize the myocardium. Fundamentally, cardiovascular MR can improve diagnosis of disease that historically has been challenging to establish with other imaging modalities. For example, decreased native T1 values appear highly specific to detect and quantify disease severity related to myocardial iron overload states or glycosphingolipid accumulation in Anderson-Fabry disease, whereas high native T1 values are observed with edema, amyloid, and other conditions. Cardiovascular MR can also improve the assessment of prognosis with parameters that relate to myocardial structure and composition that complement the familiar functional parameters around which contemporary cardiology decision making revolves. In large cohorts, extracellular volume fraction (ECV) has been shown to quantify the full extent of myocardial fibrosis in noninfarcted myocardium. ECV may predict outcomes at least as effectively as left ventricular ejection fraction. This uncommon statistical observation (of potentially being more strongly associated with outcomes than ejection fraction) suggests prime biologic importance for the cardiac interstitium that may rank highly in the hierarchy of vast myocardial changes occurring in cardiac pathophysiology. This article presents current and developing clinical applications of cardiac T1 mapping and reviews the existing evidence on their diagnostic and prognostic value in various clinical conditions. This article also contextualizes these advances and explores how T1 mapping and ECV may affect major "global" issues such as diagnosis of disease, risk stratification, and paradigms of disease, and ultimately how we conceptualize patient vulnerability.

Regulation of pumping function of the heart in developing body under changing regimens of motor activity.

PubMed

Vafina, E Z; Abzalov, R A; Abzalov, N I; Nikitin, A S; Gulyakov, A A

2014-06-01

We analyzed parameters of the pumping function of the heart in rats subjected to enhanced motor activity after a preliminary 70-day hypokinesia under conditions of α- and β-adrenergic receptor stimulation with norepinephrine followed by blockade of β-adrenergic receptor with propranolol (obsidian) and α1-adrenergic receptors with doxazosin. After norepinephrine administration, the HR and cardiac output were higher in rats with enhanced physical activity after preliminary hypokinesia than in rats with low physical activity. After propranolol administration, stroke volume and cardiac output in 100-day-old rats with limited activity were lower, and HR higher was than in rats with enhanced physical activity after preliminary 70-day hypokinesia. After administration of doxazosin, rats with limited motor activity demonstrated more pronounced changes in HR than rats with enhanced physical activity after preliminary 70-day hypokinesia.

Pulmonary arterial stiffening in COPD and its implications for right ventricular remodelling.

PubMed

Weir-McCall, Jonathan R; Liu-Shiu-Cheong, Patrick Sk; Struthers, Allan D; Lipworth, Brian J; Houston, J Graeme

2018-02-27

Pulmonary pulse wave velocity (PWV) allows the non-invasive measurement of pulmonary arterial stiffening, but has not previously been assessed in COPD. The aim of the current study was to assess PWV in COPD and its association with right ventricular (RV) remodelling. Fifty-eight participants with COPD underwent pulmonary function tests, 6-min walk test and cardiac MRI, while 21 healthy controls (HCs) underwent cardiac MRI. Thirty-two COPD patients underwent a follow-up MRI to assess for longitudinal changes in RV metrics. Cardiac MRI was used to quantify RV mass, volumes and PWV. Differences in continuous variables between the COPD and HC groups was tested using an independent t-test, and associations between PWV and right ventricular parameters was examined using Pearson's correlation coefficient. Those with COPD had reduced pulsatility (COPD (mean±SD):24.88±8.84% vs. HC:30.55±11.28%, p=0.021), pulmonary acceleration time (COPD:104.0±22.9ms vs. HC: 128.1±32.2ms, p<0.001), higher PWV (COPD:2.62±1.29ms -1 vs. HC:1.78±0.72ms -1 , p=0.001), lower RV end diastolic volume (COPD:53.6±11.1ml vs. HC:59.9±13.0ml, p=0.037) and RV stroke volume (COPD:31.9±6.9ml/m 2 vs. HC:37.1±6.2ml/m 2 , p=0.003) with no difference in mass (p=0.53). PWV was not associated with right ventricular parameters. While pulmonary vascular remodelling is present in COPD, cardiac remodelling favours reduced filling rather than increased afterload. Treatment of obstructive lung disease may have greater effect on cardiac function than treatment of pulmonary vascular disease in most COPD patients KEY POINTS: • Pulmonary pulse wave velocity (PWV) is elevated in COPD. • Pulmonary PWV is not associated with right ventricular remodelling. • Right ventricular remodelling is more in keeping with that of reduced filling.

Cardiac CT for myocardial ischaemia detection and characterization--comparative analysis.

PubMed

Bucher, A M; De Cecco, C N; Schoepf, U J; Wang, R; Meinel, F G; Binukrishnan, S R; Spearman, J V; Vogl, T J; Ruzsics, B

2014-11-01

The assessment of patients presenting with symptoms of myocardial ischaemia remains one of the most common and challenging clinical scenarios faced by physicians. Current imaging modalities are capable of three-dimensional, functional and anatomical views of the heart and as such offer a unique contribution to understanding and managing the pathology involved. Evidence has accumulated that visual anatomical coronary evaluation does not adequately predict haemodynamic relevance and should be complemented by physiological evaluation, highlighting the importance of functional assessment. Technical advances in CT technology over the past decade have progressively moved cardiac CT imaging into the clinical workflow. In addition to anatomical evaluation, cardiac CT is capable of providing myocardial perfusion parameters. A variety of CT techniques can be used to assess the myocardial perfusion. The single energy first-pass CT and dual energy first-pass CT allow static assessment of myocardial blood pool. Dynamic cardiac CT imaging allows quantification of myocardial perfusion through time-resolved attenuation data. CT-based myocardial perfusion imaging (MPI) is showing promising diagnostic accuracy compared with the current reference modalities. The aim of this review is to present currently available myocardial perfusion techniques with a focus on CT imaging in light of recent clinical investigations. This article provides a comprehensive overview of currently available CT approaches of static and dynamic MPI and presents the results of corresponding clinical trials.

Simultaneous pressure-volume measurements using optical sensors and MRI for left ventricle function assessment during animal experiment.

PubMed

Abi-Abdallah Rodriguez, Dima; Durand, Emmanuel; de Rochefort, Ludovic; Boudjemline, Younes; Mousseaux, Elie

2015-01-01

Simultaneous pressure and volume measurements enable the extraction of valuable parameters for left ventricle function assessment. Cardiac MR has proven to be the most accurate method for volume estimation. Nonetheless, measuring pressure simultaneously during MRI acquisitions remains a challenge given the magnetic nature of the widely used pressure transducers. In this study we show the feasibility of simultaneous in vivo pressure-volume acquisitions with MRI using optical pressure sensors. Pressure-volume loops were calculated while inducing three inotropic states in a sheep and functional indices were extracted, using single beat loops, to characterize systolic and diastolic performance. Functional indices evolved as expected in response to positive inotropic stimuli. The end-systolic elastance, representing the contractility index, the diastolic myocardium compliance, and the cardiac work efficiency all increased when inducing inotropic state enhancement. The association of MRI and optical pressure sensors within the left ventricle successfully enabled pressure-volume loop analysis after having respective data simultaneously recorded during the experimentation without the need to move the animal between each inotropic state. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Relationship between cardiac autonomic function and cognitive function in Alzheimer's disease.

PubMed

Nonogaki, Zen; Umegaki, Hiroyuki; Makino, Taeko; Suzuki, Yusuke; Kuzuya, Masafumi

2017-01-01

Alzheimer's disease (AD) affects many central nervous structures and neurotransmitter systems. These changes affect not only cognitive function, but also cardiac autonomic function. However, the functional relationship between cardiac autonomic function and cognition in AD has not yet been investigated. The objective of the present study was to evaluate the association between cardiac autonomic function measured by heart rate variability and cognitive function in AD. A total of 78 AD patients were recruited for this study. Cardiac autonomic function was evaluated using heart rate variability analysis. Multiple linear regression analysis was used to model the association between heart rate variability and cognitive function (global cognitive function, memory, executive function and processing speed), after adjustment for covariates. Global cognitive function was negatively associated with sympathetic modulation (low-to-high frequency power ratio). Memory performance was positively associated with parasympathetic modulation (high frequency power) and negatively associated with sympathetic modulation (low-to-high frequency power ratio). These associations were independent of age, sex, educational years, diabetes, hypertension and cholinesterase inhibitor use. Cognitive function, especially in the areas of memory, is associated with cardiac autonomic function in AD. Specifically, lower cognitive performance was found to be associated with significantly higher cardiac sympathetic and lower parasympathetic function in AD. Geriatr Gerontol Int 2017; 17: 92-98. © 2015 Japan Geriatrics Society.

A computational framework for testing arrhythmia marker sensitivities to model parameters in functionally calibrated populations of atrial cells

NASA Astrophysics Data System (ADS)

Vagos, Márcia R.; Arevalo, Hermenegild; de Oliveira, Bernardo Lino; Sundnes, Joakim; Maleckar, Mary M.

2017-09-01

Models of cardiac cell electrophysiology are complex non-linear systems which can be used to gain insight into mechanisms of cardiac dynamics in both healthy and pathological conditions. However, the complexity of cardiac models can make mechanistic insight difficult. Moreover, these are typically fitted to averaged experimental data which do not incorporate the variability in observations. Recently, building populations of models to incorporate inter- and intra-subject variability in simulations has been combined with sensitivity analysis (SA) to uncover novel ionic mechanisms and potentially clarify arrhythmogenic behaviors. We used the Koivumäki human atrial cell model to create two populations, representing normal Sinus Rhythm (nSR) and chronic Atrial Fibrillation (cAF), by varying 22 key model parameters. In each population, 14 biomarkers related to the action potential and dynamic restitution were extracted. Populations were calibrated based on distributions of biomarkers to obtain reasonable physiological behavior, and subjected to SA to quantify correlations between model parameters and pro-arrhythmia markers. The two populations showed distinct behaviors under steady state and dynamic pacing. The nSR population revealed greater variability, and more unstable dynamic restitution, as compared to the cAF population, suggesting that simulated cAF remodeling rendered cells more stable to parameter variation and rate adaptation. SA revealed that the biomarkers depended mainly on five ionic currents, with noted differences in sensitivities to these between nSR and cAF. Also, parameters could be selected to produce a model variant with no alternans and unaltered action potential morphology, highlighting that unstable dynamical behavior may be driven by specific cell parameter settings. These results ultimately suggest that arrhythmia maintenance in cAF may not be due to instability in cell membrane excitability, but rather due to tissue-level effects which promote initiation and maintenance of reentrant arrhythmia.

Association between cardiac autonomic function, oxidative stress and inflammatory response in impaired fasting glucose subjects: cross-sectional study.

PubMed

Thiyagarajan, Ramkumar; Subramanian, Senthil Kumar; Sampath, Nishanth; Madanmohan Trakroo; Pal, Pravati; Bobby, Zachariah; Paneerselvam, Sankar; Das, Ashok Kumar

2012-01-01

The worldwide burden of diabetes in 2030 is projected around 552 million. Diabetes leads to higher risk for cardiovascular diseases (CVD). Altered cardiac autonomic function (CAF) measured by heart rate variability (HRV) is observed in early stages of diabetes but the relationship between impaired fasting glucose (IFG) and HRV is still debatable. The aim of the study was to evaluate the association between CAF, oxidative stress, insulin resistance (IR), and inflammatory response in IFG subjects. Cross-sectional blinded study. Volunteers recruited from health awareness camps underwent CAF and biochemical tests. Based on fasting plasma glucose (FPG) participants (n = 123) were divided into two groups, normal fasting glucose (n = 76) and IFG (n = 47). The comparison of parameters between the groups was carried out using student t test and Mann-Whitney U test for parametric and non-parametric data respectively. The correlation between the parameters was analyzed by Spearman's rank correlation using SPSS 13.0. The resting cardiovagal modulation parameters, heart rate response to forced timed breathing, and orthostatic stress were reduced in IFG subjects. Fasting plasma lipid profile, coronary atherogenic lipid risk factors, IR, thiobarbituric acid reactive substance (TBARS), high sensitive C-reactive protein, and tumor necrosis factor alpha were increased and total antioxidant capacity (TAC) was decreased significantly in IFG group but no significant alteration was observed in high-density lipoprotein (HDL-c). Cardiovagal modulation parameters were negatively correlated with triglycerides, FPG, insulin, IR, TBARS, and inflammatory markers and positively with TAC. There is a continuous interplay between the altered CAF, hyperinsulinemia, IR, oxidative stress parameters, inflammatory response, and IFG in which one factor perpetuates another leading to the progression of disease.

Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.

PubMed

Schulte, Astrid; Lichtenstern, Christoph; Henrich, Michael; Weigand, Markus A; Uhle, Florian

2014-05-15

During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function. We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion. Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison between supervised and partly supervised cardiac rehabilitation protocols in hypertensive patients: a randomized controlled trial.

PubMed

Parreira, Larissa Barreto; de Oliveira Vitorino, Priscila Valverde; Jardim, Paulo Cesar Brandao Veiga; Sousa, Ana Luiza Lima; Jardim, Thiago Veiga; de Moura Sousa, Watila; Justo, Alberto Fenrando Oliveira; Barroso, Weimar Kunz Sebba

2018-04-13

Hypertension (HTN) is the main cause of cardiovascular diseases accounting for one third of global mortality. Physical exercise reduces the incidence and prevalence of HTN and cardiovascular morbidity and mortality. Exercises recommended for hypertensive patients include supervised cardiac rehabilitation, which occurs in rehabilitation centers, and partly supervised rehabilitation, with individual prescription of exercises conducted at patients' residences. Compare clinical and functional parameters of hypertensive patients subjected to two cardiac rehabilitation protocols: supervised and partly supervised. Hypertensive patients stage I or II were randomly divided into group one (G1) (partly supervised cardiac rehabilitation) and group two (G2) (supervised cardiac rehabilitation). All patients performed warm-up, aerobic exercise, strength training and cool-down. Participants' assessments conducted before and after intervention included: physical examination, six-minute walk test, cardiac stress test, metabolic tests, and central and peripheral blood pressure measurements. A total of 61 patients (mean age 60.3±11.3 years , 78.7% women) were randomized (30 in G1 and 31 in G2). At the end of the intervention, G1 increased 30.6 meters (p=0.004) and G2 increased 55.0 meters (p>0.001) the distance covered in the six-minute walk test. G2 showed an increase in the maximum oxygen consumption from 24.7±8.6 mlO2/Kg/min to 28.4±7.5 mlO2/Kg/min (p=0.003). Compliance with the intervention was similar in G1 and G2 (77.5±11% x 82±10%; p=0.654). Participants from both groups improved their physical fitness and showed satisfactory compliance and tolerability to the interventions. Supervised exercise was more effective in improving muscle strength and some physical fitness parameters. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adiponectin and Cardiac Hypertrophy in Acromegaly.

PubMed

Gurbulak, Sabriye; Akin, Fulya; Yerlikaya, Emrah; Yaylali, Guzin F; Topsakal, Senay; Tanriverdi, Halil; Akdag, Beyza; Kaptanoglu, Bunyamin

2016-01-01

Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be supported with other, wide, multi-centered studies.

TRPV2 knockout mice demonstrate an improved cardiac performance following myocardial infarction due to attenuated activity of peri-infarct macrophages

PubMed Central

Cohen, Lena; Hertzberg-Bigelman, Einat; Levy, Ran; Ben-Shoshan, Jeremy; Keren, Gad

2017-01-01

Background We have recently shown that the expression of the transient receptor potential vanilloid 2 channel, TRPV2, is upregulated in the peri-infarct zone 3–5 days following an acute myocardial infarction (AMI). Further analysis has demonstrated that invading monocytes maturing to macrophages merely harbor the documented elevated expression of this channel. Purpose Assess cardiac function in TRPV2-KO mice compared to TRPV2-WT following AMI and analyze the potential involvement of TRPV2-expressing macrophages in the recovery process. Methods TRPV2-KO or WT mice were induced with AMI by ligation of the left anterior descending artery (LAD). In another set of experiments, TRPV2-KO mice induced with AMI, were intravenously (IV) injected with WT or TRPV2-KO peritoneal macrophages in order to directly assess the potential contribution of TRPV2-expressing macrophages to cardiac healing. Cardiac parameters were obtained by echocardiography 1 day and 30 days post infarction. The relative changes in the ejection fraction (EF) and additional cardiac parameters between baseline (day 1) and day 30 were calculated and statistical significance was determined (SPSS). Results The in vivo study showed that while EF was significantly decreased in the WT animals between baseline and day 30, EF was only slightly and insignificantly reduced in the KO animals. Likewise LVESD and LVESA were significantly modified exclusively in the WT animals. Moreover, intravenous administration of peritoneal WT macrophages, but not KO macrophages, significantly reduced survival of post-MI TRPV2-KO mice. Conclusion The data suggest that knockout of the TRPV2 channel may attenuate macrophage-dependent pro-inflammatory processes and result in better cardiac recovery. TRPV2 may thus represent a novel therapeutic target for treatment of patients undergoing an acute MI. PMID:28481959

Effects of simvastatin on cardiohemodynamic responses to ischemia-reperfusion in isolated rat hearts.

PubMed

Zheng, Xia; Hu, Shen-Jiang

2006-03-01

Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has long been thought to exert its benefits by reducing cholesterol synthesis, and has been shown to significantly reduce cardiovascular events and mortality in patients with or without coronary artery disease. However, it is still unknown whether acute administration of simvastatin beneficially affects the cardiac function prior or during ischemia-reperfusion. The aim of this study is to evaluate the cardioprotective effect of acute simvastatin treatment on isolated rat hearts or isolated ischemia-reperfusion hearts. Hearts were isolated from male Sprague-Dawley rats and attached to a Langendorff apparatus. The isolated hearts with or without ischemia (15 min) and reperfusion (60 min) were perfused with different concentrations of simvastatin. The parameters of cardiac function (such as left ventricular developed pressure [LVDP], +dp/dt max, and -dp/dt max), heart rate, and coronary flow were recorded. Simvastatin (3-30 micromol/l) significantly increased LVDP, +dp/dt max, and -dp/dt max in isolated rat hearts perfused for 60 min. Heart rate was depressed by 30 micromol/l simvastatin and the coronary flow was increased by 10 and 30 micromol/l simvastatin. At a concentration of 100 micromol/l simvastatin, worsening of heart function and subsequent cardiac arrest occurred. Administration of simvastatin (3-30 micromol/l) significantly preserved cardiac function detected by LVDP, +dp/dt max, and -dp/dt max in the isolated ischemia/reperfused (15/60 min) rat hearts. Simvastatin also significantly decreased heart rate at 30 micromol/l, and increased coronary flow at 10 and 30 micromol/l in these rat hearts. However, the protective effect of simvastatin reverted to increased damage at 100 micromol/l. Only 3 micromol/l simvastatin pretreatment before 15/60 min ischemia-reperfusion altered LVDP, +dp/dt max, and -dp/dt max. Both heart rate and coronary flow were unaltered after simvastatin pretreatment. Since simvastatin at a concentration lower than 100 micromol/l exerted beneficial effects on cardiac function in isolated perfused rat hearts, it could be applied just after myocardial ischemia and reperfusion.

No overt structural or functional changes associated with PEG-coated gold nanoparticles accumulation with acute exposure in the mouse heart.

PubMed

Yang, Chengzhi; Yang, Hui; Wu, Jimin; Meng, Zenghui; Xing, Rui; Tian, Aiju; Tian, Xin; Guo, Lijun; Zhang, Youyi; Nie, Guangjun; Li, Zijian

2013-10-24

In this study, we investigated the cardiac biodistribution of polyethylene glycol (PEG)-coated AuNPs and their effects on cardiac function, structure and inflammation in both normal and cardiac remodeling mice. The model of cardiac remodeling was induced by subcutaneously injection of isoproterenol (ISO), a non-selective beta-adrenergic agonist, for 7 days. After AuNPs were injected intravenously in mice for 7 consecutive days, Au content in different organs was determined quantitatively by inductively coupled plasma mass spectrometry (ICP-MS), cardiac function and structure were measured by echocardiography, cardiac fibrosis was examined with picrosirius red staining, the morphology of cardiomyocytes was observed with hematoxylin and eosin (H & E) staining. The accumulation of AuNPs in hearts did not affect cardiac function or induce cardiac hypertrophy, cardiac fibrosis and cardiac inflammation under normal physiological condition. Cardiac AuNPs content was 6-fold higher in the cardiac remodeling mouse than normal mice. However, the increased accumulation of AuNPs in the heart did not aggravate ISO-induced cardiac hypertrophy, cardiac fibrosis or cardiac inflammation. These observations suggest that PEG-coated AuNPs possess excellent biocompatibility under both physiological and pathological conditions. Thus, AuNPs may be safe for cardiac patients and hold great promise for further development for various biomedical applications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prevalence and pattern of cardiac autonomic dysfunction in newly detected type 2 diabetes mellitus.

PubMed

Jyotsna, Viveka P; Sahoo, Abhay; Sreenivas, V; Deepak, K K

2009-01-01

Cardiac autonomic functions were assessed in 145 consecutive recently detected type 2 diabetics. Ninety-nine healthy persons served as controls. Criteria for normalcy were, heart rate variation during deep breathing >or=15 beats/min, deep breathing expiratory to inspiratory R-R ratio >or=1.21, Valsalva ratio >or=1.21, sustained handgrip test >or=16 mm of mercury, cold pressor test >or=10, BP response to standing or=1.04. An abnormal test was defined as the above parameters being <10 beats/min, <1.21, <1.21, or=30 mm of mercury and

Perflurooctanoic Acid Induces Developmental Cardiotoxicity in ...

EPA Pesticide Factsheets

Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxisome proliferator activated receptor alpha (PPAR_). As the cardiovascular system is crucial for embryonic survival, PFOA-induced effects on the heart may partially explain embryonic mortality. To assess impacts of PFOA exposure on the developing heart in an avian model, we used histopathology and immunohistochemical staining for myosin to assess morphological alterations in 19-day-old chicken embryo hearts after PFOA exposure. Additionally, echocardiography and cardiac myofibril ATPase activity assays were used to assess functional alterations in 1-day-old hatchling chickens following developmental PFOA exposure. Overall thinning and thinning of a dense layer of myosin in the right ventricular wall were observed in PFOA-exposed chicken embryo hearts. Alteration of multiple cardiac structural and functional parameters, including left ventricular wall thickness, left ventricular volume, heart rate, stroke volume, and ejection fraction were detected with echocardiography in the exposed hatchling chickens. Assessment of ATPase activity indicated that the ratio of cardiac myofibril calcium-independent ATPase activity to calcium-dependent ATPase activity was not affected, which suggests that d

Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress

PubMed Central

Koncsos, Gábor; Varga, Zoltán V.; Boengler, Kerstin; Rohrbach, Susanne; Li, Ling; Schlüter, Klaus-Dieter; Schreckenberg, Rolf; Radovits, Tamás; Oláh, Attila; Mátyás, Csaba; Lux, Árpád; Al-Khrasani, Mahmoud; Komlódi, Tímea; Bukosza, Nóra; Máthé, Domokos; Deres, László; Barteková, Monika; Rajtík, Tomáš; Adameová, Adriana; Szigeti, Krisztián; Helyes, Zsuzsanna; Tretter, László; Pacher, Pál; Merkely, Béla; Schulz, Rainer; Ferdinandy, Péter

2016-01-01

Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4. High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy. In prediabetic animals, a mild diastolic dysfunction was observed, the number of myocardial lipid droplets increased, and left ventricular mass and wall thickness were elevated; however, no molecular sign of fibrosis or cardiac hypertrophy was shown. In prediabetes, production of reactive oxygen species was elevated in subsarcolemmal mitochondria. Expression of mitofusin-2 was increased, while the phosphorylation of phospholamban and expression of Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3, a marker of mitophagy) decreased. However, expression of other markers of cardiac auto- and mitophagy, mitochondrial dynamics, inflammation, heat shock proteins, Ca2+/calmodulin-dependent protein kinase II, mammalian target of rapamycin, or apoptotic pathways were unchanged in prediabetes. This is the first comprehensive analysis of cardiac effects of prediabetes indicating that mild diastolic dysfunction and cardiac hypertrophy are multifactorial phenomena that are associated with early changes in mitophagy, cardiac lipid accumulation, and elevated oxidative stress and that prediabetes-induced oxidative stress originates from the subsarcolemmal mitochondria. PMID:27521417

Cumulative Burden of Myocardial Dysfunction in Cardiac Amyloidosis Assessed Using Four-Chamber Cardiac Strain.

PubMed

Kado, Yuichiro; Obokata, Masaru; Nagata, Yasufumi; Ishizu, Tomoko; Addetia, Karima; Aonuma, Kazutaka; Kurabayashi, Masahiko; Lang, Roberto M; Takeuchi, Masaaki; Otsuji, Yutaka

2016-11-01

The aim of this study was to test the hypothesis that prognosis in patients with cardiac amyloidosis is closely coupled with amyloid burden in all four cardiac chambers. The goal was to evaluate longitudinal strain (LS) in each cardiac chamber and to determine whether LS in specific cardiac chambers is preferentially associated with prognosis over conventional two-dimensional echocardiographic parameters in patients with cardiac amyloidosis. Patients with two phenotypes of left ventricular (LV) hypertrophy (cardiac amyloidosis in 55 patients and nonobstructive hypertrophic cardiomyopathy in 40 patients) and 55 healthy subjects were retrospectively enrolled for the simultaneous assessment of LS of all four cardiac chambers in the apical four-chamber view. Patients with cardiac amyloidosis were followed up to record major adverse cardiovascular events, including cardiac death, heart transplantation, nonfatal myocardial infarction, ventricular tachyarrhythmia, and exacerbation of heart failure requiring hospitalization. LS in each chamber was significantly depressed in patients with both LV hypertrophy phenotypes compared with healthy subjects. Right atrial LS was significantly lower in patients with cardiac amyloidosis than those with nonobstructive hypertrophic cardiomyopathy after adjusting for LV ejection fraction and LV mass index. During a median follow-up period of 10 months, major adverse cardiovascular events developed in 22 patients with cardiac amyloidosis. Four-chamber LS were significantly associated with major adverse cardiovascular events, with incremental value over traditional echocardiographic parameters. Cardiac amyloidosis involves all cardiac chambers, and thus, chamber-specific strain analysis may be useful to assess the total cumulative burden of cardiac dysfunction. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Music therapy, emotions and the heart: a pilot study.

PubMed

Raglio, Alfredo; Oasi, Osmano; Gianotti, Marta; Bellandi, Daniele; Manzoni, Veronica; Goulene, Karine; Imbriani, Chiara; Badiale, Marco Stramba

2012-01-01

The autonomic nervous system plays an important role in the control of cardiac function. It has been suggested that sound and music may have effects on the autonomic control of the heart inducing emotions, concomitantly with the activation of specific brain areas, i.e. the limbic area, and they may exert potential beneficial effects. This study is a prerequisite and defines a methodology to assess the relation between changes in cardiac physiological parameters such as heart rate, QT interval and their variability and the psychological responses to music therapy sessions. We assessed the cardiac physiological parameters and psychological responses to a music therapy session. ECG Holter recordings were performed before, during and after a music therapy session in 8 healthy individuals. The different behaviors of the music therapist and of the subjects have been analyzed with a specific music therapy assessment (Music Therapy Checklist). After the session mean heart rate decreased (p = 0.05), high frequency of heart rate variability tended to be higher and QTc variability tended to be lower. During music therapy session "affect attunements" have been found in all subjects but one. A significant emotional activation was associated to a higher dynamicity and variations of sound-music interactions. Our results may represent the rational basis for larger studies in diferent clinical conditions.

Characteristics of patients with a relatively greater minimum VE/VCO2 against peak VO2% and impaired exercise tolerance.

PubMed

Nakade, Taisuke; Adachi, Hitoshi; Murata, Makoto; Oshima, Shigeru

2018-05-14

Cardiopulmonary exercise testing (CPX) is used to evaluate functional capacity and assess prognosis in cardiac patients. Ventilatory efficiency (VE/VCO 2 ) reflects ventilation-perfusion mismatch; the minimum VE/VCO 2 value (minVE/VCO 2 ) is representative of pulmonary arterial blood flow in individuals without pulmonary disease. Usually, minVE/VCO 2 has a strong relationship with the peak oxygen uptake (VO 2 ), but dissociation can occur. Therefore, we investigated the relationship between minVE/VCO 2 and predicted peak VO 2 (peak VO 2 %) and evaluated the parameters associated with a discrepancy between these two parameters. A total of 289 Japanese patients underwent CPX using a cycle ergometer with ramp protocols between 2013 and 2014. Among these, 174 patients with a peak VO 2 % lower than 70% were enrolled. Patients were divided into groups based on their minVE/VCO 2 [Low group: minVE/VCO 2  < mean - SD (38.8-5.6); High group: minVE/VCO 2  > mean + SD (38.8 + 5.6)]. The characteristics and cardiac function at rest, evaluated using echocardiography, were compared between groups. The High group had a significantly lower ejection fraction, stroke volume, and cardiac output, and higher brain natriuretic peptide, tricuspid regurgitation pressure gradient, right ventricular systolic pressure, and peak early diastolic LV filling velocity/peak atrial filling velocity ratio compared with the Low group (p's < 0.01). In addition, the Low group had a significantly higher prevalence of pleural effusion than did the High group (26 vs 11%, p < 0.01). Patients with a relatively greater minVE/VCO 2 in comparison with peak VO 2 had impaired cardiac output as well as restricted pulmonary blood flow increase during exercise, partly due to accumulated pleural effusion.

Red Ginseng (Panax ginseng) Decreases Isoproterenol-Induced Cardiac Injury via Antioxidant Properties in Porcine

PubMed Central

Lim, Kyu Hee; Cho, Jae Youl; Kim, Bumseok; Bae, Bong-Seuk

2014-01-01

Abstract Red ginseng (RG, Panax ginseng) has been shown to possess various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The present study was designed to evaluate the cardioprotective potential of RG against isoproterenol (ISO)-induced myocardial infarction (MI), by assessing electrocardiographic, hemodynamic, and biochemical parameters. Male porcines were orally administered with RG (250 and 500 mg/kg) or with vehicle for 9 days, with concurrent intraperitoneal injections of ISO (20 mg/kg) on the 8th and 9th day. RG significantly attenuated ISO-induced cardiac dysfunctions as evidenced by improved ventricular hemodynamic functions and reduced ST segment and QRS complex intervals. Also, RG significantly ameliorated myocardial injury parameters such as antioxidants. Malonaldialdehyde formation was also inhibited by RG. Based on the results, it is concluded that RG possesses significant cardioprotective potential through the inhibition of oxidative stress and may serve as an adjunct in the treatment and prophylaxis of MI. PMID:24456361

Cardiac autonomic activity has a circadian rhythm in summer but not in winter in non-lactating pregnant dairy cows.

PubMed

Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

2016-03-01

This investigation was conducted to examine circadian and seasonal rhythms of heart rate and heart rate variability (HRV) by means of hour-by-hour recordings over 24h in a large population of non-lactating Holstein-Friesian pregnant cows [N=56, summer (June-July); N=61, winter (November-December)]. Data were collected during a 5-day period from each animal. Besides parameters of cardiac autonomic function [the high-frequency (HF) component of HRV and the ratio between the low-frequency (LF) and the HF components (LF/HF ratio)], the RR triangular index and Lmax were calculated. A clear circadian profile was observed for every parameter in summer. Heart rate elevated gradually with the course of the day from 7:00 to 17:00 o'clock and then slightly decreased from 18:00 to 6:00. Sympathovagal balance shifted towards sympathetic dominance during the daytime (increased LF/HF ratio), whereas parasympathetic activity was predominant during the night (increased HF). Lmax reflected a chaotic behavior of heart rate fluctuations during the afternoon in summer. Decreased values of RR triangular index indicated a sensitive period for cows between 14:00 and 16:00 o'clock in summer. During winter, except for the RR triangular (RRtri) index reflecting a high overall variability in R-R intervals between 12:00 and 23:00 o'clock, heart rate and HRV showed no periodicity over the 24-h period. The results suggest an impaired cardiac autonomic function during daytime in summer. HF, Lmax and RRtri index showed seasonal differences for both daytime and nighttime. Heart rate was higher in summer than in winter during the daytime, whereas the LF/HF ratio was higher in winter during the nighttime. Circadian and seasonal rhythms of cardiovascular function are presumably related to the differing temperature, and animal activity associated with summer and winter. As all of the investigated parameters are commonly used in bovine HRV research, these findings have practical implications for behavioral, physiological and welfare studies on dairy cattle. Copyright © 2015 Elsevier Inc. All rights reserved.

Meta-Analysis of the Relation of Baseline Right Ventricular Function to Response to Cardiac Resynchronization Therapy.

PubMed

Sharma, Abhishek; Bax, Jerome J; Vallakati, Ajay; Goel, Sunny; Lavie, Carl J; Kassotis, John; Mukherjee, Debabrata; Einstein, Andrew; Warrier, Nikhil; Lazar, Jason M

2016-04-15

Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular (LV) size and function in patients with markedly abnormal electrocardiogram QRS duration. However, relation of baseline RV function with response to CRT has not been well described. In this study, we aim to investigate the relation of baseline RV function with response to CRT as assessed by change in LV ejection fraction (EF). A systematic search of studies published from 1966 to May 31, 2015 was conducted using PubMed, CINAHL, Cochrane CENTRAL, and the Web of Science databases. Studies were included if they have reported (1) parameters of baseline RV function (tricuspid annular plane systolic excursion [TAPSE] or RVEF or RV basal strain or RV fractional area change [FAC]) and (2) LVEF before and after CRT. Random-effects metaregression was used to evaluate the effect of baseline RV function parameters and change in LVEF. Sixteen studies (n = 1,764) were selected for final analysis. Random-effects metaregression analysis showed no significant association between the magnitude of the difference in EF before and after CRT with baseline TAPSE (β = 0.005, p = 0.989); baseline RVEF (β = 0.270, p = 0.493); baseline RVFAC (β = -0.367, p = 0.06); baseline basal strain (β = -0.342, p = 0.462) after a mean follow-up period of 10.5 months. In conclusion, baseline RV function as assessed by TAPSE, FAC, basal strain, or RVEF does not determine response to CRT as assessed by change in LVEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of Left Atrial Function and Left Atrial Enhancement in Patients with Atrial Fibrillation: A Cardiac Magnetic Resonance Study

PubMed Central

Habibi, Mohammadali; Lima, Joao A.C.; Khurram, Irfan M.; Zimmerman, Stefan L.; Zipunnikov, Vadim; Fukumoto, Kotaro; Spragg, David; Ashikaga, Hiroshi; Rickard, John; Marine, Joseph E.; Calkins, Hugh; Nazarian, Saman

2015-01-01

Background Atrial fibrillation (AF) is associated with left atrial (LA) structural and functional changes. Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and feature-tracking are capable of noninvasive quantification of LA fibrosis and myocardial motion, respectively. We sought to examine the association of phasic LA function with LA enhancement in patients with AF. Methods and Results LA structure and function was measured in 90 AF patients (age 61 ± 10 years, 76% male) referred for ablation and 14 healthy volunteers. Peak global longitudinal LA strain (PLAS), LA systolic strain rate (SR-s), and early (SR-ed) and late diastolic (SR-ld) strain rates were measured using cine-CMR images acquired during sinus rhythm. The degree of LGE was quantified. Compared to patients with paroxysmal AF (60% of cohort), those with persistent AF had larger maximum LA volume index (LAVImax, 56 ± 17ml/m2 versus 49 ± 13ml/m2 p=0.036), and increased LGE (27.1± 11.7% versus 36.8 ± 14.8% p<0.001). Aside from LA active emptying fraction, all LA parameters (passive emptying fraction, PLAS, SR-s, SR-ed and SR-ld) were lower in patients with persistent AF (p< 0.05 for all). Healthy volunteers had less LGE and higher LA functional parameters compared to AF patients (p<0.05 for all). In multivariable analysis, increased LGE was associated with lower LA passive emptying fraction, PLAS, SR-s, SR-ed, and SR-ld (p<0.05 for all). Conclusions Increased LA enhancement is associated with decreased LA reservoir, conduit, and booster pump functions. Phasic measurement of LA function using feature-tracking CMR may add important information regarding the physiological importance of LA fibrosis. PMID:25652181

Cardiac tissue Doppler imaging in sports medicine.

PubMed

Krieg, Anne; Scharhag, Jürgen; Kindermann, Wilfried; Urhausen, Axel

2007-01-01

The differentiation of training-induced cardiac adaptations from pathological conditions is a key issue in sports cardiology. As morphological features do not allow for a clear delineation of early stages of relevant pathologies, the echocardiographic evaluation of left ventricular function is the technique of first choice in this regard. Tissue Doppler imaging (TDI) is a relatively recent method for the assessment of cardiac function that provides direct, local measurements of myocardial velocities throughout the cardiac cycle. Although it has shown a superior sensitivity in the detection of ventricular dysfunction in clinical and experimental studies, its application in sports medicine is still rare. Besides technical factors, this may be due to a lack in consensus on the characteristics of ventricular function in relevant conditions. For more than two decades there has been an ongoing debate on the existence of a supernormal left ventricular function in athlete's heart. While results from traditional echocardiography are conflicting, TDI studies established an improved diastolic function in endurance-trained athletes with athlete's heart compared with controls.The influence of anabolic steroids on cardiac function also has been investigated by standard echocardiographic techniques with inconsistent results. The only TDI study dealing with this topic demonstrated a significantly impaired diastolic function in bodybuilders with long-term abuse of anabolic steroids compared with strength-trained athletes without abuse of anabolic steroids and controls, respectively.Hypertrophic cardiomyopathy is the most frequent cause of sudden death in young athletes. However, in its early stages, it is difficult to distinguish from athlete's heart. By means of TDI, ventricular dysfunction in hypertrophic cardiomyopathy can be disclosed even before the development of left ventricular hypertrophy. Also, a differentiation of left ventricular hypertrophy due to hypertrophic cardiomyopathy or systemic hypertension is possible by TDI. Besides the evaluation of different forms of left ventricular hypertrophy, the diagnosis of myocarditis is also of particular importance in athletes. Today, it still requires myocardial biopsy. The analysis of focal disturbances in myocardial velocities might be a promising non-invasive method; however, systematic validation studies are lacking. An important future issue for the implementation of TDI into routine examination will be the standardisation of procedures and the establishment of significant reference values for the above-mentioned conditions. Innovative TDI parameters also merit further investigation.

Challenges in Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Godier, Amandine; Maidhof, Robert; Marsano, Anna; Martens, Timothy P.; Radisic, Milica

2010-01-01

Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Engineered constructs can also serve as high-fidelity models for studies of cardiac development and disease. In a general case, the biological potential of the cell—the actual “tissue engineer”—is mobilized by providing highly controllable three-dimensional environments that can mediate cell differentiation and functional assembly. For cardiac regeneration, some of the key requirements that need to be met are the selection of a human cell source, establishment of cardiac tissue matrix, electromechanical cell coupling, robust and stable contractile function, and functional vascularization. We review here the potential and challenges of cardiac tissue engineering for developing therapies that could prevent or reverse heart failure. PMID:19698068

Direct reconstruction of cardiac PET kinetic parametric images using a preconditioned conjugate gradient approach

PubMed Central

Rakvongthai, Yothin; Ouyang, Jinsong; Guerin, Bastien; Li, Quanzheng; Alpert, Nathaniel M.; El Fakhri, Georges

2013-01-01

Purpose: Our research goal is to develop an algorithm to reconstruct cardiac positron emission tomography (PET) kinetic parametric images directly from sinograms and compare its performance with the conventional indirect approach. Methods: Time activity curves of a NCAT phantom were computed according to a one-tissue compartmental kinetic model with realistic kinetic parameters. The sinograms at each time frame were simulated using the activity distribution for the time frame. The authors reconstructed the parametric images directly from the sinograms by optimizing a cost function, which included the Poisson log-likelihood and a spatial regularization terms, using the preconditioned conjugate gradient (PCG) algorithm with the proposed preconditioner. The proposed preconditioner is a diagonal matrix whose diagonal entries are the ratio of the parameter and the sensitivity of the radioactivity associated with parameter. The authors compared the reconstructed parametric images using the direct approach with those reconstructed using the conventional indirect approach. Results: At the same bias, the direct approach yielded significant relative reduction in standard deviation by 12%–29% and 32%–70% for 50 × 106 and 10 × 106 detected coincidences counts, respectively. Also, the PCG method effectively reached a constant value after only 10 iterations (with numerical convergence achieved after 40–50 iterations), while more than 500 iterations were needed for CG. Conclusions: The authors have developed a novel approach based on the PCG algorithm to directly reconstruct cardiac PET parametric images from sinograms, and yield better estimation of kinetic parameters than the conventional indirect approach, i.e., curve fitting of reconstructed images. The PCG method increases the convergence rate of reconstruction significantly as compared to the conventional CG method. PMID:24089922

Aortic compliance variation in long male distance triathletes: A new insight into the athlete's artery?

PubMed

Dupont, Anne-Charlotte; Poussel, Mathias; Hossu, Gabriela; Marie, Pierre-Yves; Chenuel, Bruno; Felblinger, Jacques; Mandry, Damien

2017-06-01

To assess cardiac and vascular adaptations in long-distance male triathletes and the influence of an increased training volume on these parameters. Case-control study using long-distance male triathletes (Tri) (n=12) and an age-matched cohort of sedentary volunteers (Ctrl). All participants gave an informed consent and underwent a Cardiovascular Magnetic Resonance imaging (CMR) exam to measure left and right ventricle functional parameters, and aortic parameters (surface, strain, compliance, pulse wave velocity). This exam was repeated in the triathletes' group after an increased training volume of at least 2h/week for six weeks. Compared to control volunteers, triathletes presented at baseline a typical pattern of athlete's heart (higher end-diastolic, end-systolic and stroke volumes index, p≤0.009, and lower cardiac rate, p=0.015) but similar vascular characteristics except a trend towards an enlarged ascending aorta (surface 942±106 vs 812±127mm 2 , p=0.058). Between the two visits, the triathletes increased their weekly training time from 9.67±2.43 (Tri1) to 12.15±3.01h (Tri2): no modifications were found regarding cardiac parameters, but compliance and distensibility of the ascending aorta increased, from 2.60 to 3.34mm 2 /mmHg (p=0.028) and from 3.36 to 4.40×10 -3 mmHg -1 (p=0.048) respectively. Using CMR, we showed that vascular characteristics of the ascending aorta may vary along the sport season in endurance athletes. This remodelling could be considered as a physiological adaptation, but could eventually lead to an adverse vascular remodelling. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Cardiopulmonary involvement in Fabry's disease.

PubMed

Koskenvuo, Juha W; Kantola, Ilkka M; Nuutila, Pirjo; Knuuti, Juhani; Parkkola, Riitta; Mononen, Ilkka; Hurme, Saija; Kalliokoski, Riikka; Viikari, Jorma S; Wendelin-Saarenhovi, Maria; Kiviniemi, Tuomas O; Hartiala, Jaakko J

2010-04-01

Fabry's disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipid in different tissues, including endothelial and smooth-muscle cells and cardiomyocytes. There is controversial data on cardiopulmonary involvement in Fabry's disease, because many reports are based on small and selected populations with Fabry's disease. Furthermore, the aetiology of cardiopulmonary symptoms in Fabry's disease is poorly understood. We studied cardiopulmonary involvement in seventeen patients with Fabry's disease (20-65 years, 6 men) using ECG, bicycle stress, cardiac magnetic resonance imaging, spirometry, diffusing capacity and pulmonary high-resolution computed tomography (HRCT) tests. Cardiopulmonary symptoms were compared to observed parameters in cardiopulmonary tests. Left ventricular hypertrophy (LVH) and reduced exercise capacity are the most apparent cardiac changes in both genders with Fabry's disease. ECG parameters were normal when excluding changes related to LVH. Spirometry showed mild reduction in vital capacity and forced expiratory volume in one second (FEV I), and mean values in diffusing capacity tests were within normal limits. Generally, only slight morphological pulmonary changes were detected using pulmonary HRCT, and they were not associated with changes in pulmonary function. The self-reported amount of pulmonary symptoms associated only with lower ejection fraction (P < 0.001) and longer QRS-duration (P = 0.04) of all measured cardiopulmonary parameters, whereas cardiac symptoms have no statistically significant association with any of these parameters. LVH and reduced exercise capacity are the most apparent cardiopulmonary changes in Fabry's disease but they have only a minor association to cardiopulmonary symptoms.Therefore, routine cardiopulmonary evaluation in Fabry's disease using echocardiography is maybe enough when integrated to counselling for aerobic exercise training.

Direct reconstruction of cardiac PET kinetic parametric images using a preconditioned conjugate gradient approach.

PubMed

Rakvongthai, Yothin; Ouyang, Jinsong; Guerin, Bastien; Li, Quanzheng; Alpert, Nathaniel M; El Fakhri, Georges

2013-10-01

Our research goal is to develop an algorithm to reconstruct cardiac positron emission tomography (PET) kinetic parametric images directly from sinograms and compare its performance with the conventional indirect approach. Time activity curves of a NCAT phantom were computed according to a one-tissue compartmental kinetic model with realistic kinetic parameters. The sinograms at each time frame were simulated using the activity distribution for the time frame. The authors reconstructed the parametric images directly from the sinograms by optimizing a cost function, which included the Poisson log-likelihood and a spatial regularization terms, using the preconditioned conjugate gradient (PCG) algorithm with the proposed preconditioner. The proposed preconditioner is a diagonal matrix whose diagonal entries are the ratio of the parameter and the sensitivity of the radioactivity associated with parameter. The authors compared the reconstructed parametric images using the direct approach with those reconstructed using the conventional indirect approach. At the same bias, the direct approach yielded significant relative reduction in standard deviation by 12%-29% and 32%-70% for 50 × 10(6) and 10 × 10(6) detected coincidences counts, respectively. Also, the PCG method effectively reached a constant value after only 10 iterations (with numerical convergence achieved after 40-50 iterations), while more than 500 iterations were needed for CG. The authors have developed a novel approach based on the PCG algorithm to directly reconstruct cardiac PET parametric images from sinograms, and yield better estimation of kinetic parameters than the conventional indirect approach, i.e., curve fitting of reconstructed images. The PCG method increases the convergence rate of reconstruction significantly as compared to the conventional CG method.

Effect of Head-Down Bed Rest and Artificial Gravity Countermeasure on Cardiac Autonomic and Advanced Electrocardiographic Function

NASA Technical Reports Server (NTRS)

Schlegel, T. T.; Platts, S.; Stenger, M.; Ribeiro, C.; Natapoff, A.; Howarth, M.; Evans, J.

2007-01-01

To study the effects of 21 days of head-down bed rest (HDBR), with versus without an artificial gravity (AG) countermeasure, on cardiac autonomic and advanced electrocardiographic function. Fourteen healthy men participated in the study: seven experienced 21 days of HDBR alone ("HDBR controls") and seven the same degree and duration of HDBR but with approximately 1hr daily short-arm centrifugation as an AG countermeasure ("AG-treated"). Five minute supine high-fidelity 12-lead ECGs were obtained in all subjects: 1) 4 days before HDBR; 2) on the last day of HDBR; and 3) 7 days after HDBR. Besides conventional 12-lead ECG intervals and voltages, all of the following advanced ECG parameters were studied: 1) both stochastic (time and frequency domain) and deterministic heart rate variability (HRV); 2) beat-to-beat QT interval variability (QTV); 3) T-wave morphology, including signal-averaged T-wave residua (TWR) and principal component analysis ratios; 4) other SAECG-related parameters including high frequency QRS ECG and late potentials; and 5) several advanced ECG estimates of left ventricular (LV) mass. The most important results by repeated measures ANOVA were that: 1) Heart rates, Bazett-corrected QTc intervals, TWR, LF/HF power and the alpha 1 of HRV were significantly increased in both groups (i.e., by HDBR), but with no relevant HDBR*group differences; 2) All purely "vagally-mediated" parameters of HRV (e.g., RMSSD, HF power, Poincare SD1, etc.), PR intervals, and also several parameters of LV mass (Cornell and Sokolow-Lyon voltages, spatial ventricular activation times, ventricular gradients) were all significantly decreased in both groups (i.e., by HDBR), but again with no relevant HDBR*group differences); 3) All "generalized" or "vagal plus sympathetic" parameters of stochastic HRV (i.e., SDNN, total power, LF power) were significantly more decreased in the AG-treated group than in the HDBR-only group (i.e., here there was a relevant HDBR*group difference); and 4) QTV index was also significantly more changed (increased) in the AG-treated group than in the HDBR-only group, although this was clearly due to a greater decrease in generalized HRV and not to a greater increase in QTV proper because there was no relevant HDBR*group effect for either the SDNN or the RMSSD of QTV. Brief daily AG treatment by short-arm centrifuge during each of 21 days of HDBR does not appear to protect against HDBR-related losses of cardiac autonomic function or of LV mass as estimated by ECG.

Cardiac Biomarkers in HIV-Exposed Uninfected Children: The Pediatric HIV/AIDS Cohort Study (PHACS)

PubMed Central

WILKINSON, James D.; WILLIAMS, Paige L.; LEISTER, Erin; ZELDOW, Bret; SHEARER, William T.; COLAN, Steven D.; SIBERRY, George K.; DOOLEY, Laurie B.; SCOTT, Gwendolyn B.; RICH, Kenneth C.; LIPSHULTZ, Steven E.

2014-01-01

Objectives To evaluate associations of cardiac biomarkers with in utero antiretroviral (ARV) drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children. Design and methods We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal ARV exposures, maternal-child characteristics, and echocardiographic parameters. Results Among 338 HEU children (mean age=4.3 years), 51% had at least 1 elevated cardiac biomarker. Maternal tobacco use was associated with elevated NT-proBNP (adjusted odds ratio [aOR]=2.28, P=0.02). Maternal alcohol and abacavir use were associated with elevated cTnT levels (aOR=3.56, P=0.01 and aOR=2.33, P=0.04, respectively). Among 94 children with paired echocardiogram-biomarker measurements, cTnT measurements were correlated with increased left ventricular (LV) thickness-to-dimension ratio (r=0.21, P=0.04); and elevated cTnT was associated with higher mean LV end-diastolic (ED) posterior wall thickness (P=0.04). hsCRP measurements were negatively correlated with septal thickness (r=-0.22, P=0.03) and elevated hsCRP was associated with lower mean LV contractility Z-scores (P=0.04). NT-proBNP measurements were correlated with increased LVED dimension (r=0.20, P=0.05) and elevated NT-proBNP was associated with lower mean end-systolic septal thickness (P=0.03). Conclusion Our findings suggest that cardiac biomarkers may help identify HEU children who require further cardiac evaluation including echocardiography. Potential cardiac effects of prenatal abacavir exposure in this population need further investigation. PMID:23211773

Real-time MRI guidance of cardiac interventions.

PubMed

Campbell-Washburn, Adrienne E; Tavallaei, Mohammad A; Pop, Mihaela; Grant, Elena K; Chubb, Henry; Rhode, Kawal; Wright, Graham A

2017-10-01

Cardiac magnetic resonance imaging (MRI) is appealing to guide complex cardiac procedures because it is ionizing radiation-free and offers flexible soft-tissue contrast. Interventional cardiac MR promises to improve existing procedures and enable new ones for complex arrhythmias, as well as congenital and structural heart disease. Guiding invasive procedures demands faster image acquisition, reconstruction and analysis, as well as intuitive intraprocedural display of imaging data. Standard cardiac MR techniques such as 3D anatomical imaging, cardiac function and flow, parameter mapping, and late-gadolinium enhancement can be used to gather valuable clinical data at various procedural stages. Rapid intraprocedural image analysis can extract and highlight critical information about interventional targets and outcomes. In some cases, real-time interactive imaging is used to provide a continuous stream of images displayed to interventionalists for dynamic device navigation. Alternatively, devices are navigated relative to a roadmap of major cardiac structures generated through fast segmentation and registration. Interventional devices can be visualized and tracked throughout a procedure with specialized imaging methods. In a clinical setting, advanced imaging must be integrated with other clinical tools and patient data. In order to perform these complex procedures, interventional cardiac MR relies on customized equipment, such as interactive imaging environments, in-room image display, audio communication, hemodynamic monitoring and recording systems, and electroanatomical mapping and ablation systems. Operating in this sophisticated environment requires coordination and planning. This review provides an overview of the imaging technology used in MRI-guided cardiac interventions. Specifically, this review outlines clinical targets, standard image acquisition and analysis tools, and the integration of these tools into clinical workflow. 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:935-950. © 2017 International Society for Magnetic Resonance in Medicine.

Cardiac biomarkers in HIV-exposed uninfected children.

PubMed

Wilkinson, James D; Williams, Paige L; Leister, Erin; Zeldow, Bret; Shearer, William T; Colan, Steven D; Siberry, George K; Dooley, Laurie B; Scott, Gwendolyn B; Rich, Kenneth C; Lipshultz, Steven E

2013-04-24

To evaluate associations of cardiac biomarkers with in-utero antiretroviral drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children. We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal antiretroviral drug exposures, maternal-child characteristics, and echocardiographic parameters. Among 338 HEU children (mean age 4.3 years), 51% had at least one elevated cardiac biomarker. Maternal tobacco use was associated with elevated NT-proBNP [adjusted odds ratio (aOR) 2.28, P=0.02]. Maternal alcohol and abacavir use were associated with elevated cTnT levels (aOR 3.56, P=0.01 and aOR 2.33, P=0.04, respectively). Among 94 children with paired echocardiogram-biomarker measurements, cTnT measurements were correlated with increased left-ventricular thickness-to-dimension ratio (r=0.21, P=0.04); and elevated cTnT was associated with higher mean left-ventricular end-diastolic (LVED) posterior wall thickness (P=0.04). hsCRP measurements were negatively correlated with septal thickness (r=-0.22, P=0.03) and elevated hsCRP was associated with lower mean left-ventricular contractility Z-scores (P=0.04). NT-proBNP measurements were correlated with increased LVED dimension (r=0.20, P=0.05) and elevated NT-proBNP was associated with lower mean end-systolic septal thickness (P=0.03). Our findings suggest that cardiac biomarkers may help identify HEU children who require further cardiac evaluation including echocardiography. Potential cardiac effects of prenatal abacavir exposure in this population need further investigation.

Transient Receptor Potential Vanilloid 2 Regulates Myocardial Response to Exercise

PubMed Central

Naticchioni, Mindi; Karani, Rajiv; Smith, Margaret A.; Onusko, Evan; Robbins, Nathan; Jiang, Min; Radzyukevich, Tatiana; Fulford, Logan; Gao, Xu; Apel, Ryan; Heiny, Judith; Rubinstein, Jack; Koch, Sheryl E.

2015-01-01

The myocardial response to exercise is an adaptive mechanism that permits the heart to maintain cardiac output via improved cardiac function and development of hypertrophy. There are many overlapping mechanisms via which this occurs with calcium handling being a crucial component of this process. Our laboratory has previously found that the stretch sensitive TRPV2 channels are active regulators of calcium handling and cardiac function under baseline conditions based on our observations that TRPV2-KO mice have impaired cardiac function at baseline. The focus of this study was to determine the cardiac function of TRPV2-KO mice under exercise conditions. We measured skeletal muscle at baseline in WT and TRPV2-KO mice and subjected them to various exercise protocols and measured the cardiac response using echocardiography and molecular markers. Our results demonstrate that the TRPV2-KO mouse did not tolerate forced exercise although they became increasingly exercise tolerant with voluntary exercise. This occurs as the cardiac function deteriorates further with exercise. Thus, our conclusion is that TRPV2-KO mice have impaired cardiac functional response to exercise. PMID:26356305

Coenzyme Q supplementation in pulmonary arterial hypertension

PubMed Central

Sharp, Jacqueline; Farha, Samar; Park, Margaret M.; Comhair, Suzy A.; Lundgrin, Erika L.; Tang, W.H. Wilson; Bongard, Robert D.; Merker, Marilyn P.; Erzurum, Serpil C.

2014-01-01

Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement. PMID:25180165

Comparing the Efficacy of Tadalafil Versus Placebo on Pulmonary Artery Systolic Pressure and Right Ventricular Function in Patients with Beta-Thalassaemia Intermedia.

PubMed

Jalalian, Rozita; Moghadamnia, Ali Akbar; Tamaddoni, Ahmad; Khafri, Soraya; Iranian, Mohammadreza

2017-07-01

Conventional oral therapies in the management of pulmonary hypertension in people without haemoglobinopathies are of limited value in thalassaemia patients because of toxicity and poor effectiveness. This study was conducted to assess the effect of tadalafil on pulmonary artery pressure and right ventricular systolic function in patients with beta-thalassaemia intermedia. Forty-four patients with beta-thalassaemia intermedia with pulmonary hypertension based on transthoracic echocardiography (TTE) were entered in the study. Patients with hepatic or renal insufficiency and also patients who were treated with organic nitrates or alpha-blockers were excluded. The patients were randomly divided into two groups (n=22) and they were treated for six weeks with tadalafil (40mg daily) or placebo. The pulmonary artery systolic pressure (PASP), tricuspid regurgitation velocity (TRV) and parameters related to systolic function of the right ventricle were measured by the TTE before and after treatment. Significant improvement in TRV (3.02±0.02 m/s-2.52±0.06 m/s), PASP (45.31±0.66 mmHg-34.26±1.15mmHg) and parameters related to systolic function of the right ventricle were observed in the group who received tadalafil compared to placebo (p< 0.05). Tadalafil significantly decreased PASP and TRV in patients with beta-thalassaemia intermedia. Likewise, tadalafil improved right ventricular systolic function in the patients. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Towards an atrio-ventricular delay optimization assessed by a computer model for cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Ojeda, David; Le Rolle, Virginie; Tse Ve Koon, Kevin; Thebault, Christophe; Donal, Erwan; Hernández, Alfredo I.

2013-11-01

In this paper, lumped-parameter models of the cardiovascular system, the cardiac electrical conduction system and a pacemaker are coupled to generate mitral ow pro les for di erent atrio-ventricular delay (AVD) con gurations, in the context of cardiac resynchronization therapy (CRT). First, we perform a local sensitivity analysis of left ventricular and left atrial parameters on mitral ow characteristics, namely E and A wave amplitude, mitral ow duration, and mitral ow time integral. Additionally, a global sensitivity analysis over all model parameters is presented to screen for the most relevant parameters that a ect the same mitral ow characteristics. Results provide insight on the in uence of left ventricle and atrium in uence on mitral ow pro les. This information will be useful for future parameter estimation of the model that could reproduce the mitral ow pro les and cardiovascular hemodynamics of patients undergoing AVD optimization during CRT.

Mesenchymal-endothelial-transition contributes to cardiac neovascularization

PubMed Central

Ubil, Eric; Duan, Jinzhu; Pillai, Indulekha C.L.; Rosa-Garrido, Manuel; Wu, Yong; Bargiacchi, Francesca; Lu, Yan; Stanbouly, Seta; Huang, Jie; Rojas, Mauricio; Vondriska, Thomas M.; Stefani, Enrico; Deb, Arjun

2014-01-01

Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal-transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial cell like phenotype after acute ischemic cardiac injury. Fibroblast derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast derived endothelial cells, reduces post infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal to endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial-transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair. PMID:25317562

Cardiac responses to long duration and high magnitude +Gz exposure in pilots: an observational study.

PubMed

Öztürk, Cengiz; İlbasmış, M Savaş; Akın, Ahmet

2012-12-01

In military aviation, high performance aircraft pilots are exposed to +Gz acceleration at longer durations and higher magnitude than transport/helicopter pilots. The purpose of this study was to reveal the negative or positive cardiac responses to this occupational high +Gz exposure. Our study design was cross-sectional and observational. We have evaluated 21 echocardiographic parameters of 63 pilots who applied for aircrew periodic medical examination. Of 63 pilots, 33 were grouped as high performance aircraft pilots group (Group A) and 30 were grouped as control group (Group B) whose aircraft type was transport or helicopter. Means of demographic and echocardiography parameters between two groups were compared statistically with Student's t-test, Mann- Whitney U or Chi-square test as appropriate. Among all echocardiographic parameters, mean TV A (tricuspid valve peak velocity during late diastolic filling) was significantly higher and TV E (peak velocity during early diastolic filling)/ A ratio was significantly lower for Group A pilots (p<0.05). In Group A pilots, mean TV A and TV E/A ratio were (52.12 ± 13.85) and (1.36 ± 0.30) respectively. In Group B pilots, mean TV A and TV E/A ratio were (42.61 ± 6.42) and (1.53 ± 0.20) respectively (p=0.001 for TVA and p=0.005 for TV E/A). Mean pulmonary artery pressure (PAP) of Group A pilots (32.04 ± 9.09) was higher than Group B pilots (28.76 ± 7.9) but it was not statistically significant (p>0.05). We conclude that according to the results of our study, long term +Gz exposure has no effects on cardiac morphologic and systolic functions but has effects on right ventricular diastolic functions. We have considered that these effects may be a result of chronic +Gz adaptation or high PAP levels.

Effect of right ventricular pacing on cardiac apex rotation assessed by a gyroscopic sensor.

PubMed

Marcelli, Emanuela; Cercenelli, Laura; Parlapiano, Mario; Fumero, Roberto; Bagnoli, Paola; Costantino, Maria Laura; Plicchi, Gianni

2007-01-01

To quantify cardiac apex rotation (CAR), the authors recently proposed the use of a Coriolis force sensor (gyroscope) as an alternative to other complex techniques. The aim of this study was to evaluate the effects of right ventricular (RV) pacing on CAR. A sheep heart was initially paced from the right atrium to induce a normal activation sequence at a fixed heart rate (AAI mode) and then an atrioventricular pacing was performed (DOO mode, AV delay = 60 ms). A small gyroscope was epicardially glued on the cardiac apex to measure the angular velocity (Ang V). From AAI to DOO pacing mode, an increase (+9.2%, p < 0.05) of the maximum systolic twisting velocity (Ang VMAX) and a marked decrease (-19.9%, p < 0.05) of the maximum diastolic untwisting velocity (Ang VMIN) resulted. RV pacing had negligible effects (-3.1%, p = 0.09) on the maximum angle of CAR, obtained by integrating Ang V. The hemodynamic parameters of systolic (LVdP/dtMAX) and diastolic (LVdP/dtMIN) cardiac function showed slight variations (-3.8%, p < 0.05 and +3.9%, p < 0.05, respectively). Results suggest that cardiac dyssynchrony induced by RV pacing can alter the normal physiological ventricular twist patterns, particularly affecting diastolic untwisting velocity.

Novel protective role of the circadian nuclear receptor retinoic acid-related orphan receptor-α in diabetic cardiomyopathy.

PubMed

Zhao, Yichao; Xu, Longwei; Ding, Song; Lin, Nan; Ji, Qingqi; Gao, Lingchen; Su, Yuanyuan; He, Ben; Pu, Jun

2017-04-01

Diabetic cardiomyopathy is a major complication that significantly contributes to morbidity and mortality in diabetics with few therapies. Moreover, antidiabetic drugs reported inconsistent or even adverse cardiovascular effects, suggesting that it is important to exploit novel therapeutic targets against diabetic cardiomyopathy. Here, we observed that the nuclear melatonin receptor, the retinoic acid-related orphan receptor-α (RORα), was downregulated in diabetic hearts. By utilizing a mouse line with RORα disruption, we demonstrated that RORα deficiency led to significantly augmented diastolic dysfunction and cardiac remodeling induced by diabetes. Microscopic and molecular analyses further indicated that the detrimental effects of RORα deficiency were associated with aggravated myocardial apoptosis, autophagy dysfunction, and oxidative stress by disrupting antioxidant gene expression. By contrast, restoration of cardiac RORα levels in transgenic mice significantly improved cardiac functional and structural parameters at 8 weeks after diabetes induction. Consistent with genetic manipulation, pharmacological activation of RORα by melatonin and SR1078 (a synthetic agonist) showed beneficial effects against diabetic cardiomyopathy, while the RORα inhibitor SR3335 significantly exacerbated cardiac impairments in diabetic mice. Collectively, these findings suggest that cardiac-targeted manipulation of nuclear melatonin receptor RORα may hold promise for delaying diabetic cardiomyopathy development. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessment of Cardiac Function in Fetuses of Gestational Diabetic Mothers During the Second Trimester.

PubMed

Atiq, Mehnaz; Ikram, Anum; Hussain, Batool M; Saleem, Bakhtawar

2017-06-01

Fetuses of diabetic mothers may have structural or functional cardiac abnormalities which increase morbidity and mortality. Isolated functional abnormalities have been identified in the third trimester. The aim of the present study was to assess fetal cardiac function (systolic, diastolic, and global myocardial performance) in the second trimester in mothers with gestational diabetes, and also to relate cardiac function with glycemic control. Mothers with gestational diabetes mellitus referred for fetal cardiac evaluation in the second trimester (between 19 and 24 weeks) from March 2015 to February 2016 were enrolled as case subjects in this study. Non-diabetic mothers who had a fetal echocardiogram done between 19 and 24 weeks for other indications were enrolled as controls. Functional cardiac variables showed a statistically significant difference in isovolumetric relaxation and contraction times and the myocardial performance index and mitral E/A ratios in the gestational diabetic group (p = 0.003). Mitral annular plane systolic excursion was significantly less in the diabetic group (p = 0.01). The only functional cardiac variable found abnormal in mothers with poor glycemic control was the prolonged isovolumetric relaxation time. Functional cardiac abnormalities can be detected in the second trimester in fetuses of gestational diabetic mothers and timely intervention can improve postnatal outcomes.

Training-specific changes in cardiac structure and function: a prospective and longitudinal assessment of competitive athletes.

PubMed

Baggish, Aaron L; Wang, Francis; Weiner, Rory B; Elinoff, Jason M; Tournoux, Francois; Boland, Arthur; Picard, Michael H; Hutter, Adolph M; Wood, Malissa J

2008-04-01

This prospective, longitudinal study examined the effects of participation in team-based exercise training on cardiac structure and function. Competitive endurance athletes (EA, n = 40) and strength athletes (SA, n = 24) were studied with echocardiography at baseline and after 90 days of team training. Left ventricular (LV) mass increased by 11% in EA (116 +/- 18 vs. 130 +/- 19 g/m(2); P < 0.001) and by 12% in SA (115 +/- 14 vs. 132 +/- 11 g/m(2); P < 0.001; P value for the compared Delta = NS). EA experienced LV dilation (end-diastolic volume: 66.6 +/- 10.0 vs. 74.7 +/- 9.8 ml/m(2), Delta = 8.0 +/- 4.2 ml/m(2); P < 0.001), enhanced diastolic function (lateral E': 10.9 +/- 0.8 vs. 12.4 +/- 0.9 cm/s, P < 0.001), and biatrial enlargement, while SA experience LV hypertrophy (posterior wall: 4.5 +/- 0.5 vs. 5.2 +/- 0.5 mm/m(2), P < 0.001) and diminished diastolic function (E' basal lateral LV: 11.6 +/- 1.3 vs. 10.2 +/- 1.4 cm/s, P < 0.001). Further, EA experienced right ventricular (RV) dilation (end-diastolic area: 1,460 +/- 220 vs. 1,650 +/- 200 mm/m(2), P < 0.001) coupled with enhanced systolic and diastolic function (E' basal RV: 10.3 +/- 1.5 vs. 11.4 +/- 1.7 cm/s, P < 0.001), while SA had no change in RV parameters. We conclude that participation in 90 days of competitive athletics produces significant training-specific changes in cardiac structure and function. EA develop biventricular dilation with enhanced diastolic function, while SA develop isolated, concentric left ventricular hypertrophy with diminished diastolic relaxation.

Diabetes mellitus is associated with adverse structural and functional cardiac remodelling in chronic heart failure with reduced ejection fraction.

PubMed

Walker, Andrew Mn; Patel, Peysh A; Rajwani, Adil; Groves, David; Denby, Christine; Kearney, Lorraine; Sapsford, Robert J; Witte, Klaus K; Kearney, Mark T; Cubbon, Richard M

2016-09-01

Diabetes mellitus is associated with an increased risk of death and hospitalisation in patients with chronic heart failure. Better understanding of potential underlying mechanisms may aid the development of diabetes mellitus-specific chronic heart failure therapeutic strategies. Prospective observational cohort study of 628 patients with chronic heart failure associated with left ventricular systolic dysfunction receiving contemporary evidence-based therapy. Indices of cardiac structure and function, along with symptoms and biochemical parameters, were compared in patients with and without diabetes mellitus at study recruitment and 1 year later. Patients with diabetes mellitus (24.2%) experienced higher rates of all-cause [hazard ratio, 2.3 (95% confidence interval, 1.8-3.0)] and chronic heart failure-specific mortality and hospitalisation despite comparable pharmacological and device-based therapies. At study recruitment, patients with diabetes mellitus were more symptomatic, required greater diuretic doses and more frequently had radiologic evidence of pulmonary oedema, despite higher left ventricular ejection fraction. They also exhibited echocardiographic evidence of increased left ventricular wall thickness and pulmonary arterial pressure. Diabetes mellitus was associated with reduced indices of heart rate variability and increased heart rate turbulence. During follow-up, patients with diabetes mellitus experienced less beneficial left ventricular remodelling and greater deterioration in renal function. Diabetes mellitus is associated with features of adverse structural and functional cardiac remodelling in patients with chronic heart failure. © The Author(s) 2016.

Correlations of psycho-physiological parameters influencing the physical fitness of aged women.

PubMed

Bretz, É; Kóbor-Nyakas, D É; Bretz, K J; Hrehuss, N; Radák, Z; Nyakas, Csaba

2014-12-01

Regular assessment of psycho-physiological parameters in aged subjects helps to clarify physical and mental conditions which are important in the prevention of health-endangering events to assure a healthy aging. Thirty older care female residents consented voluntarily to participate in the study. The somatic and psycho-physiological parameters recorded were handgrip force, disjunctive reaction time, balance control and whole body movement coordination, the electrocardiogram and heart rate variability. Significant correlations were found between (a) reaction time and balance control efficiency (r = -0.567, p < 0.009), (b) reaction time and movement coordination accuracy (r = -0.453, p < 0.045), (c) cardiac state and movement coordination accuracy (r = 0.545, p < 0.016), (d) cardiac stress and cardiac state (r = -0.495, p < 0.031), and (e) cardiac stress and force (r = -0.822, p < 0.045). In conclusion, for the aim of establishing basic battery tests for assessing psycho-physiological condition of physical fitness our results emphasize the importance of systematic physical activity, endurance and strength training supporting muscle force, balance control and whole-body movement coordination, in addition to improving the cardiac stress index level. The strong interrelation among these parameters allows the drawing of a more complete view regarding the health condition of aged individuals.

Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Wappel, Robert L.; Talbert, Dominique R.

2013-10-01

Tyrosine kinase inhibitors (TKi) have greatly improved the treatment and prognosis of multiple cancer types. However, unexpected cardiotoxicity has arisen in a subset of patients treated with these agents that was not wholly predicted by pre-clinical testing, which centers around animal toxicity studies and inhibition of the human Ether-à-go-go-Related Gene (hERG) channel. Therefore, we sought to determine whether a multi-parameter test panel assessing the effect of drug treatment on cellular, molecular, and electrophysiological endpoints could accurately predict cardiotoxicity. We examined how 4 FDA-approved TKi agents impacted cell viability, apoptosis, reactive oxygen species (ROS) generation, metabolic status, impedance, and ion channelmore » function in human cardiomyocytes. The 3 drugs clinically associated with severe cardiac adverse events (crizotinib, sunitinib, nilotinib) all proved to be cardiotoxic in our in vitro tests while the relatively cardiac-safe drug erlotinib showed only minor changes in cardiac cell health. Crizotinib, an ALK/MET inhibitor, led to increased ROS production, caspase activation, cholesterol accumulation, disruption in cardiac cell beat rate, and blockage of ion channels. The multi-targeted TKi sunitinib showed decreased cardiomyocyte viability, AMPK inhibition, increased lipid accumulation, disrupted beat pattern, and hERG block. Nilotinib, a second generation Bcr-Abl inhibitor, led to increased ROS generation, caspase activation, hERG block, and an arrhythmic beat pattern. Thus, each drug showed a unique toxicity profile that may reflect the multiple mechanisms leading to cardiotoxicity. This study demonstrates that a multi-parameter approach can provide a robust characterization of drug-induced cardiomyocyte damage that can be leveraged to improve drug safety during early phase development. - Highlights: • TKi with known adverse effects show unique cardiotoxicity profiles in this panel. • Crizotinib increases ROS, apoptosis, and cholesterol as well as alters beat rate. • Sunitinib inhibits AMPK, increases lipids and alters the cardiac beat pattern. • Nilotinib causes ROS and caspase activation, decreased lipids and arrhythmia. • Erlotinib did not impact ROS, caspase, or lipid levels or affect the beat pattern.« less

The heart and potassium: a banana republic.

PubMed

Khan, Ehsan; Spiers, Christine; Khan, Maria

2013-03-01

The importance of potassium in maintaining stable cardiac function is a clinically understood phenomenon. Physiologically the importance of potassium in cardiac function is described by the large number of different kinds of potassium ions channels found in the heart compared to channels and membrane transport mechanisms for other ions such as sodium and calcium. Potassium is important in physiological homeostatic control of cardiac function, but is also of relevance to the diseased state, as potassium-related effects may stabilize or destabilize cardiac function. This article aims to provide a detailed understanding of potassium-mediated cardiac function. This will help the clinical practitioner evaluate how modulation of potassium ion channels by disease and pharmacological manipulation affect the cardiac patient, thus aiding in decision making when faced with clinical problems related to potassium.

The Effect of Prolonged Physical Activity Performed during Extreme Caloric Deprivation on Cardiac Function

PubMed Central

Planer, David; Leibowitz, David; Hadid, Amir; Erlich, Tomer; Sharon, Nir; Paltiel, Ora; Jacoby, Elad; Lotan, Chaim; Moran, Daniel S.

2012-01-01

Background Endurance exercise may induce transient cardiac dysfunction. Data regarding the effect of caloric restriction on cardiac function is limited. We studied the effect of physical activity performed during extreme caloric deprivation on cardiac function. Methods Thirty-nine healthy male soldiers (mean age 20±0.3 years) were studied during a field training exercise lasted 85–103 hours, with negligible food intake and unlimited water supply. Anthropometric measurements, echocardiographic examinations and blood and urine tests were performed before and after the training exercise. Results Baseline VO2 max was 59±5.5 ml/kg/min. Participants' mean weight reduction was 5.7±0.9 kg. There was an increase in plasma urea (11.6±2.6 to 15.8±3.8 mmol/L, p<0.001) and urine osmolarity (692±212 to 1094±140 mmol/kg, p<0.001) and a decrease in sodium levels (140.5±1.0 to 136.6±2.1 mmol/L, p<0.001) at the end of the study. Significant alterations in diastolic parameters included a decrease in mitral E wave (93.6 to 83.5 cm/s; p = 0.003), without change in E/A and E/E′ ratios, and an increase in iso-volumic relaxation time (73.9 to 82.9 ms, p = 0.006). There was no change in left or right ventricular systolic function, or pulmonary arterial pressure. Brain natriuretic peptide (BNP) levels were significantly reduced post-training (median 9 to 0 pg/ml, p<0.001). There was no elevation in Troponin T or CRP levels. On multivariate analysis, BNP reduction correlated with sodium levels and weight reduction (R = 0.8, p<0.001). Conclusions Exposure to prolonged physical activity performed under caloric deprivation resulted in minor alterations of left ventricular diastolic function. BNP levels were significantly reduced due to negative water and sodium balance. PMID:22384007

The effect of prolonged physical activity performed during extreme caloric deprivation on cardiac function.

PubMed

Planer, David; Leibowitz, David; Hadid, Amir; Erlich, Tomer; Sharon, Nir; Paltiel, Ora; Jacoby, Elad; Lotan, Chaim; Moran, Daniel S

2012-01-01

Endurance exercise may induce transient cardiac dysfunction. Data regarding the effect of caloric restriction on cardiac function is limited. We studied the effect of physical activity performed during extreme caloric deprivation on cardiac function. Thirty-nine healthy male soldiers (mean age 20 ± 0.3 years) were studied during a field training exercise lasted 85-103 hours, with negligible food intake and unlimited water supply. Anthropometric measurements, echocardiographic examinations and blood and urine tests were performed before and after the training exercise. Baseline VO(2) max was 59 ± 5.5 ml/kg/min. Participants' mean weight reduction was 5.7 ± 0.9 kg. There was an increase in plasma urea (11.6 ± 2.6 to 15.8 ± 3.8 mmol/L, p<0.001) and urine osmolarity (692 ± 212 to 1094 ± 140 mmol/kg, p<0.001) and a decrease in sodium levels (140.5 ± 1.0 to 136.6 ± 2.1 mmol/L, p<0.001) at the end of the study. Significant alterations in diastolic parameters included a decrease in mitral E wave (93.6 to 83.5 cm/s; p = 0.003), without change in E/A and E/E' ratios, and an increase in iso-volumic relaxation time (73.9 to 82.9 ms, p = 0.006). There was no change in left or right ventricular systolic function, or pulmonary arterial pressure. Brain natriuretic peptide (BNP) levels were significantly reduced post-training (median 9 to 0 pg/ml, p<0.001). There was no elevation in Troponin T or CRP levels. On multivariate analysis, BNP reduction correlated with sodium levels and weight reduction (R = 0.8, p<0.001). Exposure to prolonged physical activity performed under caloric deprivation resulted in minor alterations of left ventricular diastolic function. BNP levels were significantly reduced due to negative water and sodium balance.

Macrophage Colony-Stimulating Factor Improves Cardiac Function after Ischemic Injury by Inducing Vascular Endothelial Growth Factor Production and Survival of Cardiomyocytes

PubMed Central

Okazaki, Tatsuma; Ebihara, Satoru; Asada, Masanori; Yamanda, Shinsuke; Saijo, Yoshifumi; Shiraishi, Yasuyuki; Ebihara, Takae; Niu, Kaijun; Mei, He; Arai, Hiroyuki; Yambe, Tomoyuki

2007-01-01

Macrophage colony-stimulating factor (M-CSF), known as a hematopoietic growth factor, induces vascular endothelial growth factor (VEGF) production from skeletal muscles. However, the effects of M-CSF on cardiomyocytes have not been reported. Here, we show M-CSF increases VEGF production from cardiomyocytes, protects cardiomyocytes and myotubes from cell death, and improves cardiac function after ischemic injury. In mice, M-CSF increased VEGF production in hearts and in freshly isolated cardiomyocytes, which showed M-CSF receptor expression. In rat cell line H9c2 cardiomyocytes and myotubes, M-CSF induced VEGF production via the Akt signaling pathway, and M-CSF pretreatment protected these cells from H2O2-induced cell death. M-CSF activated Akt and extracellular signal-regulated kinase signaling pathways and up-regulated downstream anti-apoptotic Bcl-xL expression in these cells. Using goats as a large animal model of myocardial infarction, we found that M-CSF treatment after the onset of myocardial infarction by permanent coronary artery ligation promoted angiogenesis in ischemic hearts but did not reduce the infarct area. M-CSF pretreatment of the goat myocardial infarction model by coronary artery occlusion-reperfusion improved cardiac function, as assessed by hemodynamic parameters and echocardiography. These results suggest M-CSF might be a novel therapeutic agent for ischemic heart disease. PMID:17717142

The Living Heart Project: A robust and integrative simulator for human heart function.

PubMed

Baillargeon, Brian; Rebelo, Nuno; Fox, David D; Taylor, Robert L; Kuhl, Ellen

2014-11-01

The heart is not only our most vital, but also our most complex organ: Precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. While numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. Here we present a proof-of-concept simulator for a four-chamber human heart model created from computer topography and magnetic resonance images. We illustrate the governing equations of excitation-contraction coupling and discretize them using a single, unified finite element environment. To illustrate the basic features of our model, we visualize the electrical potential and the mechanical deformation across the human heart throughout its cardiac cycle. To compare our simulation against common metrics of cardiac function, we extract the pressure-volume relationship and show that it agrees well with clinical observations. Our prototype model allows us to explore and understand the key features, physics, and technologies to create an integrative, predictive model of the living human heart. Ultimately, our simulator will open opportunities to probe landscapes of clinical parameters, and guide device design and treatment planning in cardiac diseases such as stenosis, regurgitation, or prolapse of the aortic, pulmonary, tricuspid, or mitral valve.

An exploratory study on the efficacy and safety of a BCAA preparation used in combination with cardiac rehabilitation for patients with chronic heart failure.

PubMed

Takata, Munenori; Amiya, Eisuke; Watanabe, Masafumi; Hosoya, Yumiko; Nakayama, Atsuko; Fujiwara, Takayuki; Taya, Masanobu; Oguri, Gaku; Hyodo, Kanako; Takayama, Naoko; Takano, Nami; Mashiko, Tomoe; Uemura, Yukari; Komuro, Issei

2017-07-27

Sarcopenia is generally complicated with patients with chronic heart failure (CHF) and its presence negatively affects the course of heart failure, however effective nutritional intervention had not been elucidated yet. The primary objective of this study is to explore whether the addition of a branched-chain amino acid (BCAA) preparation for cardiac rehabilitation (CR) of patients with CHF further improves cardiopulmonary functions, skeletal muscle functions, and metabolism in comparison with conventional CR. This is a randomized, parallel-group comparative study. The elderly patients that were participated in CR and complicated with left ventricular systolic or diastolic dysfunction are randomized into two groups, CR + BCAA and CR. 20 weeks later, the second randomization is performed, which divide subjects into two groups with and without BCAA intervention without CR. Primary outcome measure is the rate of change of the anaerobic threshold workload from baseline to post-intervention. Secondary outcome include parameters of exercise capacity, cardiac function and psychological status. In the current study the effect of a promising new intervention, BCAA, will be assessed to determine whether its addition to CR improve exercise capacity in patients with heart failure, who are generally complicated with sarcopenia. This clinical trial was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR; JPRN-UMIN R000022440 ).

German cardiac CT registry: indications, procedural data and clinical consequences in 7061 patients undergoing cardiac computed tomography.

PubMed

Marwan, Mohamed; Achenbach, Stephan; Korosoglou, Grigorios; Schmermund, Axel; Schneider, Steffen; Bruder, Oliver; Hausleiter, Jörg; Schroeder, Stephen; Barth, Sebastian; Kerber, Sebastian; Leber, Alexander; Moshage, Werner; Senges, Jochen

2018-05-01

Cardiac computed tomography permits quantification of coronary calcification as well as detection of coronary artery stenoses after contrast enhancement. Moreover, cardiac CT offers high-resolution morphologic and functional imaging of cardiac structures which is valuable for various structural heart disease interventions and electrophysiology procedures. So far, only limited data exist regarding the spectrum of indications, image acquisition parameters as well as results and clinical consequences of cardiac CT examinations using state-of-the-art CT systems in experienced centers. Twelve cardiology centers with profound expertise in cardiovascular imaging participated in the German Cardiac CT Registry. Criteria for participation included adequate experience in cardiac CT as well of the availability of a 64-slice or newer CT system. Between 2009 and 2014, 7061 patients were prospectively enrolled. For all cardiac CT examinations, patient parameters, procedural data, indication and clinical consequences of the examination were documented. Mean patient age was 61 ± 12 years, 63% were males. The majority (63%) of all cardiac CT examinations were performed in an outpatient setting, 37% were performed during an inpatient stay. 91% were elective and 9% were scheduled in an acute setting. In most examinations (48%), reporting was performed by cardiologists, in 4% by radiologists and in 47% of the cases as a consensus reading. Cardiac CT was limited to native acquisitions for assessment of coronary artery calcification in 9% of patients, only contrast-enhanced coronary CT angiography was performed in 16.6% and combined native and contrast-enhanced coronary CT angiography was performed in 57.7% of patients. Non-coronary cardiac CT examinations constituted 16.6% of all cases. Coronary artery calcification assessment was performed using prospectively ECG-triggered acquisition in 76.9% of all cases. The median dose length product (DLP) was 42 mGy cm (estimated effective radiation dose of 0.6 mSv). Coronary CT angiography was performed using prospectively ECG-triggered acquisition in 77.3% of all cases. Tube voltage was 120 kV in 67.8% of patients and 100 kV in 30.7% of patients, with a resultant median DLP of 256 mGy cm (estimated effective dose of 3.6 mSv). Clinical consequences of cardiac CT were as follows: in 46.8% of the cases, invasive coronary angiography could be avoided; ischemia testing was recommended in 4.7% of the cases, invasive coronary angiography was recommended in 16.4% of the cases and change in medication in 21.6% of the examinations. Cardiac CT is performed in the majority of patients for non-invasive evaluation of the coronary arteries. CT frequently resulted in medication change, and otherwise planned downstream testing including invasive angiography could be avoided in a high percentage of patients. Radiation exposure in experienced centers is relatively low.

Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

PubMed Central

Liu, Li; Goldberg, Ira J.

2015-01-01

Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

Left atrial strain predicts hemodynamic parameters in cardiovascular patients.

PubMed

Hewing, Bernd; Theres, Lena; Spethmann, Sebastian; Stangl, Karl; Dreger, Henryk; Knebel, Fabian

2017-08-01

We aimed to evaluate the predictive value of left atrial (LA) reservoir, conduit, and contractile function parameters as assessed by speckle tracking echocardiography (STE) for invasively measured hemodynamic parameters in a patient cohort with myocardial and valvular diseases. Sixty-nine patients undergoing invasive hemodynamic assessment were enrolled into the study. Invasive hemodynamic parameters were obtained by left and right heart catheterization. Transthoracic echocardiography assessment of LA reservoir, conduit, and contractile function was performed by STE. Forty-nine patients had sinus rhythm (SR) and 20 patients had permanent atrial fibrillation (AF). AF patients had significantly reduced LA reservoir function compared to SR patients. In patients with SR, LA reservoir, conduit, and contractile function inversely correlated with pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure, and mean pulmonary artery pressure (PAP), and showed a moderate association with cardiac index. In AF patients, there were no significant correlations between LA reservoir function and invasively obtained hemodynamic parameters. In SR patients, LA contractile function with a cutoff value of 16.0% had the highest diagnostic accuracy (area under the curve, AUC: 0.895) to predict PCWP ≥18 mm Hg compared to the weaker diagnostic accuracy of average E/E' ratio with an AUC of 0.786 at a cutoff value of 14.3. In multivariate analysis, LA contractile function remained significantly associated with PCWP ≥18 mm Hg. In a cohort of patients with a broad spectrum of cardiovascular diseases LA strain shows a valuable prediction of hemodynamic parameters, specifically LV filling pressures, in the presence of SR. © 2017, Wiley Periodicals, Inc.

A novel cardiac MR chamber volume model for mechanical dyssynchrony assessment

NASA Astrophysics Data System (ADS)

Song, Ting; Fung, Maggie; Stainsby, Jeffrey A.; Hood, Maureen N.; Ho, Vincent B.

2009-02-01

A novel cardiac chamber volume model is proposed for the assessment of left ventricular mechanical dyssynchrony. The tool is potentially useful for assessment of regional cardiac function and identification of mechanical dyssynchrony on MRI. Dyssynchrony results typically from a contraction delay between one or more individual left ventricular segments, which in turn leads to inefficient ventricular function and ultimately heart failure. Cardiac resynchronization therapy has emerged as an electrical treatment of choice for heart failure patients with dyssynchrony. Prior MRI techniques have relied on assessments of actual cardiac wall changes either using standard cine MR images or specialized pulse sequences. In this abstract, we detail a semi-automated method that evaluates dyssynchrony based on segmental volumetric analysis of the left ventricular (LV) chamber as illustrated on standard cine MR images. Twelve sectors each were chosen for the basal and mid-ventricular slices and 8 sectors were chosen for apical slices for a total of 32 sectors. For each slice (i.e. basal, mid and apical), a systolic dyssynchrony index (SDI) was measured. SDI, a parameter used for 3D echocardiographic analysis of dyssynchrony, was defined as the corrected standard deviation of the time at which minimal volume is reached in each sector. The SDI measurement of a healthy volunteer was 3.54%. In a patient with acute myocardial infarction, the SDI measurements 10.98%, 16.57% and 1.41% for basal, mid-ventricular and apical LV slices, respectively. Based on published 3D echocardiogram reference threshold values, the patient's SDI corresponds to moderate basal dysfunction, severe mid-ventricular dysfunction, and normal apical LV function, which were confirmed on echocardiography. The LV chamber segmental volume analysis model and SDI is feasible using standard cine MR data and may provide more reliable assessment of patients with dyssynchrony especially if the LV myocardium is thin or if the MR images have spatial resolution insufficient for proper resolution of wall thickness-features problematic for dyssynchrony assessment using existing MR techniques.

Serial changes in anatomy and ventricular function on dual-source cardiac computed tomography after the Norwood procedure for hypoplastic left heart syndrome.

PubMed

Goo, Hyun Woo

2017-12-01

Accurate evaluation of anatomy and ventricular function after the Norwood procedure in hypoplastic left heart syndrome is important for treatment planning and prognostication, but echocardiography and cardiac MRI have limitations. To assess serial changes in anatomy and ventricular function on dual-source cardiac CT after the Norwood procedure for hypoplastic left heart syndrome. In 14 consecutive patients with hypoplastic left heart syndrome, end-systolic and end-diastolic phase cardiac dual-source CT was performed before and early (average: 1 month) after the Norwood procedure, and repeated late (median: 4.5 months) after the Norwood procedure in six patients. Ventricular functional parameters and indexed morphological measurements including pulmonary artery size, right ventricular free wall thickness, and ascending aorta size on cardiac CT were compared between different time points. Moreover, morphological features including ventricular septal defect, endocardial fibroelastosis and coronary ventricular communication were evaluated on cardiac CT. Right ventricular function and volumes remained unchanged (indexed end-systolic and end-diastolic volumes: 38.9±14.0 vs. 41.1±21.5 ml/m 2 , P=0.7 and 99.5±30.5 vs. 105.1±33.0 ml/m 2 , P=0.6; ejection fraction: 60.1±7.3 vs. 63.8±7.0%, P=0.1, and indexed stroke volume: 60.7±18.0 vs. 64.0±15.6 ml/m 2 , P=0.5) early after the Norwood procedure, but function was decreased (ejection fraction: 64.2±2.6 vs. 58.1±7.1%, P=0.01) and volume was increased (indexed end-systolic and end-diastolic volumes: 39.2±14.9 vs. 68.9±20.6 ml/m 2 , P<0.003 and 107.8±36.5 vs. 162.9±36.2 ml/m 2 , P<0.006, and indexed stroke volume: 68.6±21.7 vs. 94.0±21.3 ml/m 2 , P=0.02) later. Branch pulmonary artery size showed a gradual decrease without asymmetry after the Norwood procedure. Right and left pulmonary artery stenoses were identified in 21.4% (3/14) of the patients. Indexed right ventricular free wall thickness showed a significant increase early after the Norwood procedure (25.5±3.5 vs. 34.8±5.1 mm/m 2 , P=0.01) and then a significant decrease late after the Norwood procedure (34.8±5.1 vs. 27.2±4.2 mm/m 2 , P<0.0001). The hypoplastic ascending aorta smaller than 2 mm in diameter was identified in 21.4% (3/14) of the patients. Ventricular septal defect (n=3), endocardial fibroelastosis (n=2) and coronary ventricular communication (n=1) were detected on cardiac CT. Cardiac CT can be used to assess serial changes in anatomy and ventricular function after the Norwood procedure in patients with hypoplastic left heart syndrome.

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

2009-01-01

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

Analysis of pressure head-flow loops of pulsatile rotodynamic blood pumps.

PubMed

Jahren, Silje E; Ochsner, Gregor; Shu, Fangjun; Amacher, Raffael; Antaki, James F; Vandenberghe, Stijn

2014-04-01

The clinical importance of pulsatility is a recurring topic of debate in mechanical circulatory support. Lack of pulsatility has been identified as a possible factor responsible for adverse events and has also demonstrated a role in myocardial perfusion and cardiac recovery. A commonly used method for restoring pulsatility with rotodynamic blood pumps (RBPs) is to modulate the speed profile, synchronized to the cardiac cycle. This introduces additional parameters that influence the (un)loading of the heart, including the timing (phase shift) between the native cardiac cycle and the pump pulses, and the amplitude of speed modulation. In this study, the impact of these parameters upon the heart-RBP interaction was examined in terms of the pressure head-flow (HQ) diagram. The measurements were conducted using a rotodynamic Deltastream DP2 pump in a validated hybrid mock circulation with baroreflex function. The pump was operated with a sinusoidal speed profile, synchronized to the native cardiac cycle. The simulated ventriculo-aortic cannulation showed that the level of (un)loading and the shape of the HQ loops strongly depend on the phase shift. The HQ loops displayed characteristic shapes depending on the phase shift. Increased contribution of native contraction (increased ventricular stroke work [WS ]) resulted in a broadening of the loops. It was found that the previously described linear relationship between WS and the area of the HQ loop for constant pump speeds becomes a family of linear relationships, whose slope depends on the phase shift. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

Myocardin-related transcription factors are required for cardiac development and function

PubMed Central

Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

2016-01-01

Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor

PubMed Central

Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

2017-01-01

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p<0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, p<0.05) and ejection fraction (82%±3% vs 60%±5%, p<0.05). Treatment with telmisartan provided a comparable level of protection as compared with edaravone in all the parameters measured. Taken together, edaravone treatment ameliorates cardiac fibrosis and improves left ventricular function in the pressure overload rat model, potentially via suppressing the AT1 receptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure. PMID:29081650

Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor.

PubMed

Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

2017-01-01

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p <0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, p <0.05) and ejection fraction (82%±3% vs 60%±5%, p <0.05). Treatment with telmisartan provided a comparable level of protection as compared with edaravone in all the parameters measured. Taken together, edaravone treatment ameliorates cardiac fibrosis and improves left ventricular function in the pressure overload rat model, potentially via suppressing the AT1 receptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure.

Virtual reality exercise on a home-based phase III cardiac rehabilitation program, effect on executive function, quality of life and depression, anxiety and stress: a randomized controlled trial.

PubMed

Vieira, Ágata; Melo, Cristina; Machado, Jorge; Gabriel, Joaquim

2018-02-01

To analyse the effect of a six-month home-based phase III cardiac rehabilitation (CR) specific exercise program, performed in a virtual reality (Kinect) or conventional (booklet) environment, on executive function, quality of life and depression, anxiety and stress of subjects with coronary artery disease. A randomized controlled trial was conducted with subjects, who had completed phase II, randomly assigned to intervention group 1 (IG1), whose program encompassed the use of Kinect (n = 11); or intervention group 2 (IG2), a paper booklet (n = 11); or a control group (CG), only subjected to the usual care (n = 11). The three groups received education on cardiovascular risk factors. The assessed parameters, at baseline (M0), 3 (M1) and 6 months (M2), were executive function, control and integration in the implementation of an adequate behaviour in relation to a certain objective, specifically the ability to switch information (Trail Making Test), working memory (Verbal Digit Span test), and selective attention and conflict resolution ability (Stroop test), quality of life (MacNew questionnaire) and depression, anxiety and stress (Depression, Anxiety and Stress Scale 21). Descriptive and inferential statistical measures were used, significance level was set at .05. The IG1 revealed significant improvements, in the selective attention and conflict resolution ability, in comparison with the CG in the variable difference M0 - M2 (p = .021) and in comparison with the IG2 in the variable difference M1 - M2 and M0 - M2 (p = .001 and p = .002, respectively). No significant differences were found in the quality of life, and depression, anxiety and stress. The virtual reality format had improved selective attention and conflict resolution ability, revealing the potential of CR, specifically with virtual reality exercise, on executive function. Implications for Rehabilitation In cardiac rehabilitation, especially in phase III, it is important to develop and to present alternative strategies, as virtual reality using the Kinect in a home context. Taking into account the relationship between the improvement of the executive function with physical exercise, it is relevant to access the impact of a cardiac rehabilitation program on the executive function. Enhancing the value of the phase III of cardiac rehabilitation.

FEV manoeuvre induced changes in breath VOC compositions: an unconventional view on lung function tests

NASA Astrophysics Data System (ADS)

Sukul, Pritam; Schubert, Jochen K.; Oertel, Peter; Kamysek, Svend; Taunk, Khushman; Trefz, Phillip; Miekisch, Wolfram

2016-06-01

Breath volatile organic compound (VOC) analysis can open a non-invasive window onto pathological and metabolic processes in the body. Decades of clinical breath-gas analysis have revealed that changes in exhaled VOC concentrations are important rather than disease specific biomarkers. As physiological parameters, such as respiratory rate or cardiac output, have profound effects on exhaled VOCs, here we investigated VOC exhalation under respiratory manoeuvres. Breath VOCs were monitored by means of real-time mass-spectrometry during conventional FEV manoeuvres in 50 healthy humans. Simultaneously, we measured respiratory and hemodynamic parameters noninvasively. Tidal volume and minute ventilation increased by 292 and 171% during the manoeuvre. FEV manoeuvre induced substance specific changes in VOC concentrations. pET-CO2 and alveolar isoprene increased by 6 and 21% during maximum exhalation. Then they decreased by 18 and 37% at forced expiration mirroring cardiac output. Acetone concentrations rose by 4.5% despite increasing minute ventilation. Blood-borne furan and dimethyl-sulphide mimicked isoprene profile. Exogenous acetonitrile, sulphides, and most aliphatic and aromatic VOCs changed minimally. Reliable breath tests must avoid forced breathing. As isoprene exhalations mirrored FEV performances, endogenous VOCs might assure quality of lung function tests. Analysis of exhaled VOC concentrations can provide additional information on physiology of respiration and gas exchange.

FEV manoeuvre induced changes in breath VOC compositions: an unconventional view on lung function tests

PubMed Central

Sukul, Pritam; Schubert, Jochen K.; Oertel, Peter; Kamysek, Svend; Taunk, Khushman; Trefz, Phillip; Miekisch, Wolfram

2016-01-01

Breath volatile organic compound (VOC) analysis can open a non-invasive window onto pathological and metabolic processes in the body. Decades of clinical breath-gas analysis have revealed that changes in exhaled VOC concentrations are important rather than disease specific biomarkers. As physiological parameters, such as respiratory rate or cardiac output, have profound effects on exhaled VOCs, here we investigated VOC exhalation under respiratory manoeuvres. Breath VOCs were monitored by means of real-time mass-spectrometry during conventional FEV manoeuvres in 50 healthy humans. Simultaneously, we measured respiratory and hemodynamic parameters noninvasively. Tidal volume and minute ventilation increased by 292 and 171% during the manoeuvre. FEV manoeuvre induced substance specific changes in VOC concentrations. pET-CO2 and alveolar isoprene increased by 6 and 21% during maximum exhalation. Then they decreased by 18 and 37% at forced expiration mirroring cardiac output. Acetone concentrations rose by 4.5% despite increasing minute ventilation. Blood-borne furan and dimethyl-sulphide mimicked isoprene profile. Exogenous acetonitrile, sulphides, and most aliphatic and aromatic VOCs changed minimally. Reliable breath tests must avoid forced breathing. As isoprene exhalations mirrored FEV performances, endogenous VOCs might assure quality of lung function tests. Analysis of exhaled VOC concentrations can provide additional information on physiology of respiration and gas exchange. PMID:27311826

[Fluid therapy in cardiac surgery. An update].

PubMed

Boix, E; Vicente, R; Pérez-Artacho, J

2014-01-01

The anesthetist has 2 major tools for optimizing haemodynamics in cardiac surgery: Vasoactive drugs and the intravascular volume. It is necessary to identify which patients would benefit from one or the other therapies for a suitable response to treatment. Hemodynamic monitoring with the different existing parameters (pressure, volumetric static, volumetric functional and echocardiography) allows the management of these patients to be optimized. In this article a review is presented on the most recent and relevant publications, and the different tools available to control the management of the fluid therapy in this context, and to suggest a few guidelines for the haemodynamics monitoring of patients submitted to cardiac surgery. A systematic search has been made in PubMed, limiting the results to the publications over the last five years up to February 2012. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Multimodality Imaging in Cardiooncology

PubMed Central

Pizzino, Fausto; Vizzari, Giampiero; Qamar, Rubina; Bomzer, Charles; Carerj, Scipione; Khandheria, Bijoy K.

2015-01-01

Cardiotoxicity represents a rising problem influencing prognosis and quality of life of chemotherapy-treated patients. Anthracyclines and trastuzumab are the drugs most commonly associated with development of a cardiotoxic effect. Heart failure, myocardial ischemia, hypertension, myocarditis, and thrombosis are typical manifestation of cardiotoxicity by chemotherapeutic agents. Diagnosis and monitoring of cardiac side-effects of cancer treatment is of paramount importance. Echocardiography and nuclear medicine methods are widely used in clinical practice and left ventricular ejection fraction is the most important parameter to asses myocardial damage secondary to chemotherapy. However, left ventricular ejection decrease is a delayed phenomenon, occurring after a long stage of silent myocardial damage that classic imaging methods are not able to detect. New imaging techniques including three-dimensional echocardiography, speckle tracking echocardiography, and cardiac magnetic resonance have demonstrated high sensitivity in detecting the earliest alteration of left ventricular function associated with future development of chemotherapy-induced cardiomyopathy. Early diagnosis of cardiac involvement in cancer patients can allow for timely and adequate treatment management and the introduction of cardioprotective strategies. PMID:26300915

Cardiac surgical outcomes improvement led by a physician champion working with a nurse clinical coordinator.

PubMed

Stanford, John R; Swaney-Berghoff, Laurie; Recht, Kimberly

2012-01-01

Cardiac surgical outcomes improvement in a community hospital was driven by a physician champion working with a nurse clinical coordinator. Specific system improvements implemented were (1) nurse checklists of vital signs, cardiovascular function parameters, and life support appliance operation; (2) use of the EuroSCORE system of preoperative patient risk assessment; (3) monthly morbidity and mortality conferences; and (4) daily patient progress tracking. The hospital received 1 star (bottom 12% of hospitals for quality outcomes) from the Society of Thoracic Surgeons Adult Cardiac Database in 2006 prior to program inception, 2 stars (middle 76% of hospitals for quality outcomes) in 2007 and 2008, and 3 stars (top 12% of hospitals) in 2009. The physician and nurse together combined a strategy for clinical improvement with the cultural practices at the hospital to ensure that system improvements approved at the strategic level were implemented at the point of care. Both strategy and culture must be addressed to ensure patient outcomes improvement.

Electromagnetic interference in cardiac rhythm management devices.

PubMed

Sweesy, Mark W; Holland, James L; Smith, Kerry W

2004-01-01

Clinicians caring for cardiac device patients with implanted pacemakers or cardioverter defibrillators (ICDs) are frequently asked questions by their patients concerning electromagnetic interference (EMI) sources and the devices. EMI may be radiated or conducted and may be present in many different forms including (but not limited to) radiofrequency waves, microwaves, ionizing radiation, acoustic radiation, static and pulsed magnetic fields, and electric currents. Manufacturers have done an exemplary job of interference protection with device features such as titanium casing, signal filtering, interference rejection circuits, feedthrough capacitors, noise reversion function, and programmable parameters. Nevertheless, EMI remains a real concern and a potential danger. Many factors influence EMI including those which the patient can regulate (eg, distance from and duration of exposure) and some the patient cannot control (eg, intensity of the EMI field, signal frequency). Potential device responses are many and range from simple temporary oversensing to permanent device damage Several of the more common EMI-generating devices and their likely effects on cardiac devices are considered in the medical, home, and daily living and work environments.

Effect of low-level laser-treated mesenchymal stem cells on myocardial infarction.

PubMed

El Gammal, Zaynab H; Zaher, Amr M; El-Badri, Nagwa

2017-09-01

Cardiovascular disease is the leading cause of death worldwide. Although cardiac transplantation is considered the most effective therapy for end-stage cardiac diseases, it is limited by the availability of matching donors and the complications of the immune suppressive regimen used to prevent graft rejection. Application of stem cell therapy in experimental animal models was shown to reverse cardiac remodeling, attenuate cardiac fibrosis, improve heart functions, and stimulate angiogenesis. The efficacy of stem cell therapy can be amplified by low-level laser radiation. It is well established that the bio-stimulatory effect of low-level laser is influenced by the following parameters: wavelength, power density, duration, energy density, delivery time, and the type of irradiated target. In this review, we evaluate the available experimental data on treatment of myocardial infarction using low-level laser. Eligible papers were characterized as in vivo experimental studies that evaluated the use of low-level laser therapy on stem cells in order to attenuate myocardial infarction. The following descriptors were used separately and in combination: laser therapy, low-level laser, low-power laser, stem cell, and myocardial infarction. The assessed low-level laser parameters were wavelength (635-804 nm), power density (6-50 mW/cm 2 ), duration (20-150 s), energy density (0.96-1 J/cm 2 ), delivery time (20 min-3 weeks after myocardial infarction), and the type of irradiated target (bone marrow or in vitro-cultured bone marrow mesenchymal stem cells). The analysis focused on the cardioprotective effect of this form of therapy, the attenuation of scar tissue, and the enhancement of angiogenesis as primary targets. Other effects such as cell survival, cell differentiation, and homing are also included. Among the evaluated protocols using different parameters, the best outcome for treating myocardial infarction was achieved by treating the bone marrow by one dose of low-level laser with 804 nm wavelength and 1 J/cm 2 energy density within 4 h of the infarction. This approach increased stem cell survival, proliferation, and homing. It has also decreased the infarct size and cell apoptosis, leading to enhanced heart functions. These effects were stable for 6 weeks. However, more studies are still required to assess the effects of low-level laser on the genetic makeup of the cell, the nuclei, and the mitochondria of mesenchymal stromal cells (MSCs).

The comparative effects of 3% saline and 0.5M sodium lactate on cardiac function:a randomised, crossover study in volunteers.

PubMed

Nalos, Marek; Kholodniak, Euguenia; Smith, Louise; Orde, Sam; Ting, Iris; Slama, Michel; Seppelt, Ian; McLean, Anthony S; Huang, Stephen

2018-06-01

To investigate the metabolic and cardiac effects of intravenous administration of two hypertonic solutions - 3% saline (SAL) and 0.5M sodium lactate (LAC). A randomised, doubleblind, crossover study in ten human volunteers. Intravenous bolus of either SAL or LAC at 3 mL/kg over 20 min followed by a 2 mL/kg infusion over 60 min. Acid base parameters and echocardiographic indices of cardiac function, cardiac output (CO), left ventricular ejection fraction (LVEF) and mitral annular peak systolic velocity (Sm) before and after infusion of SAL or LAC. Despite haemodilution, we observed an increase in sodium (139 ± 2 mmol/L to 142 ± 2 mmol/L in both groups) and respective anions, chloride (106 ± 2 mmol/L to 112 ± 3 mmol/L) and lactate (1.01 ± 0.28 mmol/L to 2.38 ± 0.38 mmol/L) with SAL and LAC, respectively. The pH (7.37 ± 0.03 to 7.45 ± 0.03; P < 0.01) and simplified strong ion difference (SID) (36.3 ± 4.6 mmol/L to 39.2 ± 3.6 mmol/L; P < 0.01) increased during the LAC infusion. The pH was unchanged, but SID decreased during SAL infusion (36.3 ± 2.5 mmol/L to 33.9 ± 3.1 mmol/L; P = 0.01). Both solutions led to an increase in preload and cardiac function, CO (4.36 ± 0.79 L/min to 4.98 ± 1.37 L/ min v 4.62 ± 1.30 L/min to 5.13 ± 1.44 L/min), LVEF (61 ± 6% to 63 ± 8% v 64 ± 6% to 68 ± 7%). The averaged Sm improved in the LAC group as compared with the SAL group (0.088 ± 0.008 to 0.096 ± 0.016 v 0.086 ± 0.012 to 0.082 ± 0.012; P = 0.032). The administration of SAL or LAC has opposing effects on acid base variables such as SID. Hypertonic fluid infusion lead to increased cardiac preload and performance with Sm, suggesting better left ventricular systolic function during LAC as compared with SAL. Lactated hypertonic solutions should be evaluated as resuscitation fluids.

The Value of Quality Improvement Process in the Detection and Correction of Common Errors in Echocardiographic Hemodynamic Parameters in a Busy Echocardiography Laboratory

PubMed Central

Fanari, Zaher; Choudhry, Usman I; Reddy, Vivek K; Eze-Nliam, Chete; Hammami, Sumaya; Kolm, Paul; Weintraub, William S.; Marshall, Erik S

2015-01-01

Background Accurate assessment of cardiac structures, ventricular function, and hemodynamics are essential for any echocardiographic laboratory. Quality Improvement (QI) processes described by the American Society of Echocardiography (ASE) and the Intersocietal Commission (IAC) should be instrumental in reaching this goal. Methods All patients undergoing transthoracic echocardiogram (TTE) followed by cardiac catheterization within 24 hours at Christiana Care Health System in 2011 and 2012 were identified, with 126 and 133 cases respectively. Hemodynamic parameters of diastolic function, Pulmonary Artery Systolic Pressure (PASP) on TTE correlated poorly with catheterization in 2011. An educational process was developed and implemented at quarterly QI meetings based on ASE and IAC recommendations to target frequently encountered errors and provide methods for improved performance. The hemodynamic parameters were then re-examined in 2012 post-intervention. Results Following the QI process, there was significant improvement in the correlation between invasive and echocardiographic hemodynamic measurements in both systolic and diastolic function, and PASP. This reflected in significant better correlations between echo and cath LVEF [R = 0.88, ICC=0.87 vs. R = 0.85, ICC=0.85; p <0.001], Average E/E’ and of left Ventricle End Diastolic Pressure (LVEDP) [R = 0.62vs. R = 0.09, p = 0.006] and a better correlation for PASP [R= 0.77, ICC=0.77 vs. R = 0.30, ICC=0.31; p = 0.05] in 2012 compared to 2011. Conclusion The QI process, as recommended by ASE and IAC, can allow for identification as well as rectification of quality issues in a large regional academic medical center hospital. PMID:26033297

Chronic Dosing with Membrane Sealant Poloxamer 188 NF Improves Respiratory Dysfunction in Dystrophic Mdx and Mdx/Utrophin-/- Mice.

PubMed

Markham, Bruce E; Kernodle, Stace; Nemzek, Jean; Wilkinson, John E; Sigler, Robert

2015-01-01

Poloxamer 188 NF (national formulary (NF) grade of P-188) improves cardiac muscle function in the mdx mouse and golden retriever muscular dystrophy models. However in vivo effects on skeletal muscle have not been reported. We postulated that P-188 NF might protect diaphragm muscle membranes from contraction-induced injury in mdx and mdx/utrophin-/- (dko) muscular dystrophy models. In the first study 7-month old mdx mice were treated for 22 weeks with subcutaneous (s.c.) injections of saline or P-188 NF at 3 mg/Kg. In the second, dkos were treated with saline or P-188 NF (1 mg/Kg) for 8 weeks beginning at age 3 weeks. Prednisone was the positive control in both studies. Respiratory function was monitored using unrestrained whole body plethysmography. P-188 NF treatment affected several respiratory parameters including tidal volume/BW and minute volume/BW in mdx mice. In the more severe dko model, P-188 NF (1 mg/Kg) significantly slowed the decline in multiple respiratory parameters compared with saline-treated dko mice. Prednisone's effects were similar to those seen with P-188 NF. Diaphragms from P-188 NF or prednisone treated mdx and dko mice showed signs of muscle fiber protection including less centralized nuclei, less variation in fiber size, greater fiber density, and exhibited a decreased amount of collagen deposition. P-188 NF at 3 mg/Kg s.c. also improved parameters of systolic and diastolic function in mdx mouse hearts. These results suggest that P-188 NF may be useful in treating respiratory and cardiac dysfunction, the leading causes of death in Duchenne muscular dystrophy patients.

Chronic Dosing with Membrane Sealant Poloxamer 188 NF Improves Respiratory Dysfunction in Dystrophic Mdx and Mdx/Utrophin-/- Mice

PubMed Central

Markham, Bruce E.; Kernodle, Stace; Nemzek, Jean; Wilkinson, John E.; Sigler, Robert

2015-01-01

Poloxamer 188 NF (national formulary (NF) grade of P-188) improves cardiac muscle function in the mdx mouse and golden retriever muscular dystrophy models. However in vivo effects on skeletal muscle have not been reported. We postulated that P-188 NF might protect diaphragm muscle membranes from contraction-induced injury in mdx and mdx/utrophin-/- (dko) muscular dystrophy models. In the first study 7-month old mdx mice were treated for 22 weeks with subcutaneous (s.c.) injections of saline or P-188 NF at 3 mg/Kg. In the second, dkos were treated with saline or P-188 NF (1 mg/Kg) for 8 weeks beginning at age 3 weeks. Prednisone was the positive control in both studies. Respiratory function was monitored using unrestrained whole body plethysmography. P-188 NF treatment affected several respiratory parameters including tidal volume/BW and minute volume/BW in mdx mice. In the more severe dko model, P-188 NF (1 mg/Kg) significantly slowed the decline in multiple respiratory parameters compared with saline-treated dko mice. Prednisone’s effects were similar to those seen with P-188 NF. Diaphragms from P-188 NF or prednisone treated mdx and dko mice showed signs of muscle fiber protection including less centralized nuclei, less variation in fiber size, greater fiber density, and exhibited a decreased amount of collagen deposition. P-188 NF at 3 mg/Kg s.c. also improved parameters of systolic and diastolic function in mdx mouse hearts. These results suggest that P-188 NF may be useful in treating respiratory and cardiac dysfunction, the leading causes of death in Duchenne muscular dystrophy patients. PMID:26248188

The Value of Quality Improvement Process in the Detection and Correction of Common Errors in Echocardiographic Hemodynamic Parameters in a Busy Echocardiography Laboratory.

PubMed

Fanari, Zaher; Choudhry, Usman I; Reddy, Vivek K; Eze-Nliam, Chete; Hammami, Sumaya; Kolm, Paul; Weintraub, William S; Marshall, Erik S

2015-12-01

Accurate assessment of cardiac structures, ventricular function, and hemodynamics is essential for any echocardiographic laboratory. Quality improvement (QI) processes described by the American Society of Echocardiography (ASE) and the Intersocietal Commission (IAC) should be instrumental in reaching this goal. All patients undergoing transthoracic echocardiogram (TTE) followed by cardiac catheterization within 24 hours at Christiana Care Health System in 2011 and 2012 were identified, with 126 and 133 cases, respectively. Hemodynamic parameters of diastolic function and pulmonary artery systolic pressure (PASP) on TTE correlated poorly with catheterization in 2011. An educational process was developed and implemented at quarterly QI meetings based on ASE and IAC recommendations to target frequently encountered errors and provide methods for improved performance. The hemodynamic parameters were then reexamined in 2012 postintervention. Following the QI process, there was significant improvement in the correlation between invasive and echocardiographic hemodynamic measurements in both systolic and diastolic function, and PASP. This reflected in significant better correlations between echo and cath LVEF [R = 0.88, ICC = 0.87 vs. R = 0.85, ICC = 0.85; P < 0.001], average E/E' and of left ventricle end-diastolic pressure (LVEDP) [R = 0.62 vs. R = 0.09, P = 0.006] and a better correlation for PASP [R = 0.77, ICC = 0.77 vs. R = 0.30, ICC = 0.31; P = 0.05] in 2012 compared to 2011. The QI process, as recommended by ASE and IAC, can allow for identification as well as rectification of quality issues in a large regional academic medical center hospital. © 2015, Wiley Periodicals, Inc.

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

PubMed Central

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-01-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function.

PubMed

Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

2016-06-01

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

Longitudinal association of short-term, metronome-paced heart rate variability and echocardiographically assessed cardiac structure at a 4-year follow-up: results from the prospective, population-based CARLA cohort.

PubMed

Medenwald, Daniel; Swenne, Cees A; Frantz, Stefan; Nuding, Sebastian; Kors, Jan A; Pietzner, Diana; Tiller, Daniel; Greiser, Karin H; Kluttig, Alexander; Haerting, Johannes

2017-12-01

To assess the value of cardiac structure/function in predicting heart rate variability (HRV) and the possibly predictive value of HRV on cardiac parameters. Baseline and 4-year follow-up data from the population-based CARLA cohort were used (790 men, 646 women, aged 45-83 years at baseline and 50-87 years at follow-up). Echocardiographic and HRV recordings were performed at baseline and at follow-up. Linear regression models with a quadratic term were used. Crude and covariate adjusted estimates were calculated. Missing values were imputed by means of multiple imputation. Heart rate variability measures taken into account consisted of linear time and frequency domain [standard deviation of normal-to-normal intervals (SDNN), high-frequency power (HF), low-frequency power (LF), LF/HF ratio] and non-linear measures [detrended fluctuation analysis (DFA1), SD1, SD2, SD1/SD2 ratio]. Echocardiographic parameters considered were ventricular mass index, diastolic interventricular septum thickness, left ventricular diastolic dimension, left atrial dimension systolic (LADS), and ejection fraction (Teichholz). A negative quadratic relation between baseline LADS and change in SDNN and HF was observed. The maximum HF and SDNN change (an increase of roughly 0.02%) was predicted at LADS of 3.72 and 3.57 cm, respectively, while the majority of subjects experienced a decrease in HRV. There was no association between further echocardiographic parameters and change in HRV, and there was no evidence of a predictive value of HRV in the prediction of changes in cardiac structure. In the general population, LADS predicts 4-year alteration in SDNN and HF non-linearly. Because of the novelty of the result, analyses should be replicated in other populations. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response.

PubMed

Takatori, Osamu; Usui, Soichiro; Okajima, Masaki; Kaneko, Shuichi; Ootsuji, Hiroshi; Takashima, Shin-Ichiro; Kobayashi, Daisuke; Murai, Hisayoshi; Furusho, Hiroshi; Takamura, Masayuki

2017-05-01

The unfolded protein response (UPR) plays a pivotal role in ischemia-reperfusion (I/R) injury in various organs such as heart, brain, and liver. Sodium 4-phenylbutyrate (PBA) reportedly acts as a chemical chaperone that reduces UPR. In the present study, we evaluated the effect of PBA on reducing the UPR and protecting against myocardial I/R injury in mice. Male C57BL/6 mice were subjected to 30-minute myocardial I/R, and were treated with phosphate-buffered saline (as a vehicle) or PBA. At 4 hours after reperfusion, mice treated with PBA had reduced serum cardiac troponin I levels and numbers of apoptotic cells in left ventricles (LVs) in myocardial I/R. Infarct size had also reduced in mice treated with PBA at 48 hours after reperfusion. At 2 hours after reperfusion, UPR markers, including eukaryotic initiation of the factor 2α-subunit, activating transcription factor-6, inositol-requiring enzyme-1, glucose-regulated protein 78, CCAAT/enhancer-binding protein (C/EBP) homologous protein, and caspase-12, were significantly increased in mice treated with vehicle compared to sham-operated mice. Administration of PBA significantly reduced the I/R-induced increases of these markers. Cardiac function and dimensions were assessed at 21 days after I/R. Sodium 4-phenylbutyrate dedicated to the improvement of cardiac parameters deterioration including LV end-diastolic diameter and LV fractional shortening. Consistently, PBA reduced messenger RNA expression levels of cardiac remodeling markers such as collagen type 1α1, brain natriuretic peptide, and α skeletal muscle actin in LV at 21 days after I/R. Unfolded protein response mediates myocardial I/R injury. Administration of PBA reduces the UPR, apoptosis, infarct size, and preserved cardiac function. Hence, PBA may be a therapeutic option to attenuate myocardial I/R injury in clinical practice.

SIRT1 activation attenuates diastolic dysfunction by reducing cardiac fibrosis in a model of anthracycline cardiomyopathy.

PubMed

Cappetta, Donato; Esposito, Grazia; Piegari, Elena; Russo, Rosa; Ciuffreda, Loreta Pia; Rivellino, Alessia; Berrino, Liberato; Rossi, Francesco; De Angelis, Antonella; Urbanek, Konrad

2016-02-15

Doxorubicin (DOXO) is an effective anti-neoplastic drug but its clinical benefits are hampered by cardiotoxicity. Oxidative stress, apoptosis and myocardial fibrosis mediate the anthracycline cardiomyopathy. ROS trigger TGF-β pathway that activates cardiac fibroblasts promoting fibrosis. Myocardial stiffness contributes to diastolic dysfunction, less studied aspect of anthracycline cardiomyopathy. Considering the role of SIRT1 in the inhibition of the TGF-β/SMAD3 pathway, resveratrol (RES), a SIRT1 activator, might improve cardiac function by interfering with the development of cardiac fibrosis in a model of DOXO-induced cardiomyopathy. F344 rats received a cumulative dose of 15 mg/kg of DOXO in 2 weeks or DOXO+RES (DOXO and RES, 2.5mg/kg/day, concomitantly for 2 weeks and then RES alone for 1 more week). The effects of RES on cardiac fibroblasts were also tested in vitro. Along with systolic dysfunction, DOXO was also responsible of diastolic abnormalities. Myocardial stiffness correlated with fibroblast activation and collagen deposition. DOXO+RES co-treatment significantly improved ± dP/dt and, more interestingly, ameliorated end-diastolic pressure/volume relationship. Treatment with RES resulted in reduced fibrosis and fibroblast activation and, most importantly, the mortality rate was significantly reduced in DOXO+RES group. Fibroblasts isolated from DOXO+RES-treated rats, in which SIRT1 was upregulated, showed decreased levels of TGF-β and pSMAD3/SMAD3 when compared to cells isolated from DOXO-exposed hearts. Our findings reveal a key role of SIRT1 in supporting animal survival and functional parameters of the heart. SIRT1 activation by interfering with fibrogenesis can improve relaxation properties of myocardium and attenuate myocardial remodeling related to chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Serca2a and Na{sup +}/Ca{sup 2+} exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nascimento, Andrews Marques do; Lima, Ewelyne Mira

Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt{sub max}, − dP/dt{sub min} and Tau) were assessed in the leftmore » ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na{sup +}/Ca{sup 2+} exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. - Highlights: • ND and resistive exercise enhanced the cardiac function and increased expression of cytosolic calcium regulatory components.« less

Assessment of left ventricular myocardial deformation by cardiac MRI strain imaging reveals myocardial dysfunction in patients with primary cardiac tumors.

PubMed

Chen, Jing; Yang, Zhi-Gang; Xu, Hua-Yan; Shi, Ke; Guo, Ying-Kun

2018-02-15

To assess left ventricular myocardial deformation in patients with primary cardiac tumors. MRI was retrospectively performed in 61 patients, including 31 patients with primary cardiac tumors and 30 matched normal controls. Left ventricular strain and function parameters were then assessed by MRI-tissue tracking. Differences between the tumor group and controls, left and right heart tumor groups, left ventricular wall tumor and non-left ventricular wall tumor groups, and tumors with and without LV enlargement groups were assessed. Finally, the correlations among tumor diameter, myocardial strain, and LV function were analyzed. Left ventricular myocardial strain was milder for tumor group than for normal group. Peak circumferential strain (PCS) and its diastolic strain rate, longitudinal strains (PLS) and its diastolic strain rates, and peak radial systolic and diastolic velocities of the right heart tumor group were lower than those of the left heart tumor group (all p<0.050), but the peak radial systolic strain rate of the former was higher than that of the latter (p=0.017). The corresponding strains were lower in the left ventricular wall tumor groups than in the non-left ventricular wall tumor group (p<0.050). Peak radial systolic velocities were generally higher for tumors with LV enlargement than for tumors without LV enlargement (p<0.050). Peak radial strain, PCS, and PLS showed important correlations with the left ventricular ejection fraction (all p<0.050). MRI-tissue tracking is capable of quantitatively assessing left ventricular myocardial strain to reveal sub-clinical abnormalities of myocardial contractile function. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure.

PubMed

Kobayashi, Shigeki; Susa, Takehisa; Tanaka, Takeo; Murakami, Wakako; Fukuta, Seiko; Okuda, Shinichi; Doi, Masahiro; Wada, Yasuaki; Nao, Tomoko; Yamada, Jutaro; Okamura, Takayuki; Yano, Masafumi; Matsuzaki, Masunori

2012-01-01

The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia. Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12 beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6 L·min(-1)·m(-2); pulmonary capillary wedge pressure [PCWP], 26±8 mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0 µg·kg(-1)·min(-1); i.v.), which is an ultra-short-acting β(1)-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5 µg·kg(-1)·min(-1)) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0 µg·kg(-1)·min(-1)) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5 µg·kg(-1)·min(-1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate pressure product, filling time/RR, E/e', and Tei index were significantly improved. A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR.

Vitamin D receptor agonist VS-105 improves cardiac function in the presence of enalapril in 5/6 nephrectomized rats

PubMed Central

Chen, Yung-wu; Wessale, Jerry L.

2014-01-01

Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to manage hyperparathyroidism secondary to chronic kidney disease (CKD). Patients with CKD experience extremely high risks of cardiovascular morbidity and mortality. Clinical observations show that VDRA therapy may be associated with cardio-renal protective and survival benefits in patients with CKD. The 5/6 nephrectomized (NX) Sprague-Dawley rat with established uremia exhibits elevated serum parathyroid hormone (PTH), hypertension, and abnormal cardiac function. Treatment of 5/6 NX rats with VS-105, a novel VDRA (0.05 and 0.5 μg/kg po by gavage), once daily for 8 wk in the presence or absence of enalapril (30 mg/kg po via drinking water) effectively suppressed serum PTH without raising serum calcium. VS-105 alone reduced systolic blood pressure (from 174 ± 6 to 145 ± 9 mmHg, P < 0.05) as effectively as enalapril (from 174 ± 6 to 144 ± 7 mmHg, P < 0.05). VS-105 improved cardiac functional parameters such as E/A ratio, ejection fraction, and fractional shortening with or without enalapril. Enalapril or VS-105 alone significantly reduced left ventricular hypertrophy (LVH); VS-105 plus enalapril did not further reduce LVH. VS-105 significantly reduced both cardiac and renal fibrosis. The lack of hypercalcemic toxicity of VS-105 is due to its lack of effects on stimulating intestinal calcium transport and inducing the expression of intestinal calcium transporter genes such as Calb3 and TRPV6. These studies demonstrate that VS-105 is a novel VDRA that may provide cardiovascular benefits via VDR activation. Clinical studies are required to confirm the cardiovascular benefits of VS-105 in CKD. PMID:25503724

Triiodothyronine increases myocardial function and pyruvate entry into the citric acid cycle after reperfusion in a model of infant cardiopulmonary bypass

PubMed Central

Olson, Aaron K.; Bouchard, Bertrand; Ning, Xue-Han; Isern, Nancy; Rosiers, Christine Des

2012-01-01

Triiodothyronine (T3) supplementation improves clinical outcomes in infants after cardiac surgery using cardiopulmonary bypass by unknown mechanisms. We utilized a translational model of infant cardiopulmonary bypass to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC), thereby providing the energy support for improved cardiac function after ischemia-reperfusion (I/R). Neonatal piglets received intracoronary [2-13Carbon(13C)]pyruvate for 40 min (8 mM) during control aerobic conditions (control) or immediately after reperfusion (I/R) from global hypothermic ischemia. A third group (I/R-Tr) received T3 (1.2 μg/kg) during reperfusion. We assessed absolute CAC intermediate levels and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC) and anaplerotic carboxylation (PC) using [2-13C]pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and 13C-nuclear magnetic resonance spectroscopy. When compared with I/R, T3 (group I/R-Tr) increased cardiac power and oxygen consumption after I/R while elevating flux of both PDC and PC (∼4-fold). Although neither I/R nor I/R-Tr modified absolute CAC levels, T3 inhibited I/R-induced reductions in their molar percent enrichment. Furthermore, 13C-labeling of CAC intermediates suggests that T3 may decrease entry of unlabeled carbons at the level of oxaloacetate through anaplerosis or exchange reaction with asparate. T3 markedly enhances PC and PDC fluxes, thereby providing potential substrate for elevated cardiac function after reperfusion. This T3-induced increase in pyruvate fluxes occurs with preservation of the CAC intermediate pool. Our labeling data raise the possibility that T3 reduces reliance on amino acids for anaplerosis after reperfusion. PMID:22180654

Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

PubMed

Gao, Jun-Qing; Xie, Yun; Yang, Wei; Zheng, Jian-Pu; Liu, Zong-Jun

2017-01-01

Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress.

PubMed

Koncsos, Gábor; Varga, Zoltán V; Baranyai, Tamás; Boengler, Kerstin; Rohrbach, Susanne; Li, Ling; Schlüter, Klaus-Dieter; Schreckenberg, Rolf; Radovits, Tamás; Oláh, Attila; Mátyás, Csaba; Lux, Árpád; Al-Khrasani, Mahmoud; Komlódi, Tímea; Bukosza, Nóra; Máthé, Domokos; Deres, László; Barteková, Monika; Rajtík, Tomáš; Adameová, Adriana; Szigeti, Krisztián; Hamar, Péter; Helyes, Zsuzsanna; Tretter, László; Pacher, Pál; Merkely, Béla; Giricz, Zoltán; Schulz, Rainer; Ferdinandy, Péter

2016-10-01

Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4 High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy. In prediabetic animals, a mild diastolic dysfunction was observed, the number of myocardial lipid droplets increased, and left ventricular mass and wall thickness were elevated; however, no molecular sign of fibrosis or cardiac hypertrophy was shown. In prediabetes, production of reactive oxygen species was elevated in subsarcolemmal mitochondria. Expression of mitofusin-2 was increased, while the phosphorylation of phospholamban and expression of Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3, a marker of mitophagy) decreased. However, expression of other markers of cardiac auto- and mitophagy, mitochondrial dynamics, inflammation, heat shock proteins, Ca 2+ /calmodulin-dependent protein kinase II, mammalian target of rapamycin, or apoptotic pathways were unchanged in prediabetes. This is the first comprehensive analysis of cardiac effects of prediabetes indicating that mild diastolic dysfunction and cardiac hypertrophy are multifactorial phenomena that are associated with early changes in mitophagy, cardiac lipid accumulation, and elevated oxidative stress and that prediabetes-induced oxidative stress originates from the subsarcolemmal mitochondria. Copyright © 2016 the American Physiological Society.

And the beat goes on: maintained cardiovascular function during aging in the longest-lived rodent, the naked mole-rat

PubMed Central

Grimes, Kelly M.; Reddy, Anilkumar K.; Lindsey, Merry L.

2014-01-01

The naked mole-rat (NMR) is the longest-lived rodent known, with a maximum lifespan potential (MLSP) of >31 years. Despite such extreme longevity, these animals display attenuation of many age-associated diseases and functional changes until the last quartile of their MLSP. We questioned if such abilities would extend to cardiovascular function and structure in this species. To test this, we assessed cardiac functional reserve, ventricular morphology, and arterial stiffening in NMRs ranging from 2 to 24 years of age. Dobutamine echocardiography (3 μg/g ip) revealed no age-associated changes in left ventricular (LV) function either at baseline or with exercise-like stress. Baseline and dobutamine-induced LV pressure parameters also did not change. Thus the NMR, unlike other mammals, maintains cardiac reserve with age. NMRs showed no cardiac hypertrophy, evidenced by no increase in cardiomyocyte cross-sectional area or LV dimensions with age. Age-associated arterial stiffening does not occur since there are no changes in aortic blood pressures or pulse-wave velocity. Only LV interstitial collagen deposition increased 2.5-fold from young to old NMRs (P < 0.01). However, its effect on LV diastolic function is likely minor since NMRs experience attenuated age-related increases in diastolic dysfunction in comparison with other species. Overall, these findings conform to the negligible senescence phenotype, as NMRs largely stave off cardiovascular changes for at least 75% of their MLSP. This suggests that using a comparative strategy to find factors that change with age in other mammals but not NMRs could provide novel targets to slow or prevent cardiovascular aging in humans. PMID:24906918

Cardiovascular reflexes during rest and exercise modified by gravitational stresses

NASA Astrophysics Data System (ADS)

Bonde-petersen, Flemming

The hypotheses tested were whether variations in central venous pressure via the low pressure baroreceptors would take over or modify the arterial baroreceptor function, and further to which extent local and "whole body" hydrostatic stresses influence blood flow distribution. We investigated total forearm and skin blood flow (venous occlusion plethysmography and 133-Xe clearance) and cardiac output (rebreathing method) among other parameters. Hypo-and hypergravitational stresses were simulated by LBNP, LBPP, water immersion and lowering of the arm. The changes in flow distribution in the arm were ascribed to arterial baroreceptor function and not to low pressure baroreceptor activity. The enhancement of venous return during water immersion increased exercise tolerance during heat stress presumably due both to increased stroke volume and decreased venous pooling. The response to sustained handgrip exercise during LBNP and LBPP was not different from control measurements and the effects explained by arterial baroreceptor function. Application of exercise and local hydrostatic stresses in combination with gravitational stresses represent an interesting model for further study of the mechanisms behind the distribution of cardiac output to the peripheral organs.

Cardiac magnetic resonance imaging parameters as surrogate endpoints in clinical trials of acute myocardial infarction

PubMed Central

2011-01-01

Cardiac magnetic resonance (CMR) offers a variety of parameters potentially suited as surrogate endpoints in clinical trials of acute myocardial infarction such as infarct size, myocardial salvage, microvascular obstruction or left ventricular volumes and ejection fraction. The present article reviews each of these parameters with regard to the pathophysiological basis, practical aspects, validity, reliability and its relative value (strengths and limitations) as compared to competitive modalities. Randomized controlled trials of acute myocardial infarction which have used CMR parameters as a primary endpoint are presented. PMID:21917147

Kruppel-like factor 15 is required for the cardiac adaptive response to fasting.

PubMed

Sugi, Keiki; Hsieh, Paishiun N; Ilkayeva, Olga; Shelkay, Shamanthika; Moroney, Bridget; Baadh, Palvir; Haynes, Browning; Pophal, Megan; Fan, Liyan; Newgard, Christopher B; Prosdocimo, Domenick A; Jain, Mukesh K

2018-01-01

Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand. Here we show that cardiac KLF15 is required for the normal cardiac response to fasting. Specifically, we find that cardiac function is impaired upon fasting in systemic and cardiac specific Klf15-null mice. Further, cardiac specific Klf15-null mice display a fasting-dependent accumulation of long chain acylcarnitine species along with a decrease in expression of the carnitine translocase Slc25a20. Treatment with a diet high in short chain fatty acids relieves the KLF15-dependent long chain acylcarnitine accumulation and impaired cardiac function in response to fasting. Our observations establish KLF15 as a critical mediator of the cardiac adaptive response to fasting through its regulation of myocardial lipid utilization.

Comparison of usefulness of N-terminal pro-brain natriuretic peptide as an independent predictor of cardiac function among admission cardiac serum biomarkers in patients with anterior wall versus nonanterior wall ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Haeck, Joost D E; Verouden, Niels J W; Kuijt, Wichert J; Koch, Karel T; Van Straalen, Jan P; Fischer, Johan; Groenink, Maarten; Bilodeau, Luc; Tijssen, Jan G P; Krucoff, Mitchell W; De Winter, Robbert J

2010-04-15

The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction. The NT-pro-BNP levels were divided into quartiles and correlated with left ventricular function and infarct size measured by CMR imaging at 4 to 6 months. Compared to the lower quartiles, patients with nonanterior wall myocardial infarction in the highest quartile of NT-pro-BNP (> or = 260 pg/ml) more often had a greater left ventricular end-systolic volume (68 vs 39 ml/m(2), p <0.001), a lower left ventricular ejection fraction (42% vs 54%, p <0.001), a larger infarct size (9 vs 4 g/m(2), p = 0.002), and a larger number of transmural segments (11% of segments vs 3% of segments, p <0.001). Multivariate analysis revealed that a NT-pro-BNP level of > or = 260 pg/ml was the strongest independent predictor of left ventricular ejection fraction in patients with nonanterior wall myocardial infarction compared to the other serum biomarkers (beta = -5.8; p = 0.019). In conclusion, in patients with nonanterior wall myocardial infarction undergoing primary percutaneous coronary intervention, an admission NT-pro-BNP level of > or = 260 pg/ml was a strong, independent predictor of left ventricular function assessed by CMR imaging at follow-up. Our findings suggest that NT-pro-BNP, a widely available biomarker, might be helpful in the early risk stratification of patients with nonanterior wall myocardial infarction. Copyright 2010 Elsevier Inc. All rights reserved.

Integrating atlas and graph cut methods for right ventricle blood-pool segmentation from cardiac cine MRI

NASA Astrophysics Data System (ADS)

Dangi, Shusil; Linte, Cristian A.

2017-03-01

Segmentation of right ventricle from cardiac MRI images can be used to build pre-operative anatomical heart models to precisely identify regions of interest during minimally invasive therapy. Furthermore, many functional parameters of right heart such as right ventricular volume, ejection fraction, myocardial mass and thickness can also be assessed from the segmented images. To obtain an accurate and computationally efficient segmentation of right ventricle from cardiac cine MRI, we propose a segmentation algorithm formulated as an energy minimization problem in a graph. Shape prior obtained by propagating label from an average atlas using affine registration is incorporated into the graph framework to overcome problems in ill-defined image regions. The optimal segmentation corresponding to the labeling with minimum energy configuration of the graph is obtained via graph-cuts and is iteratively refined to produce the final right ventricle blood pool segmentation. We quantitatively compare the segmentation results obtained from our algorithm to the provided gold-standard expert manual segmentation for 16 cine-MRI datasets available through the MICCAI 2012 Cardiac MR Right Ventricle Segmentation Challenge according to several similarity metrics, including Dice coefficient, Jaccard coefficient, Hausdorff distance, and Mean absolute distance error.

Estrogen regulates histone deacetylases to prevent cardiac hypertrophy

PubMed Central

Pedram, Ali; Razandi, Mahnaz; Narayanan, Ramesh; Dalton, James T.; McKinsey, Timothy A.; Levin, Ellis R.

2013-01-01

The development and progression of cardiac hypertrophy often leads to heart failure and death, and important modulators of hypertrophy include the histone deacetylase proteins (HDACs). Estrogen inhibits cardiac hypertrophy and progression in animal models and humans. We therefore investigated the influence of 17-β-estradiol on the production, localization, and functions of prohypertrophic (class I) and antihypertrophic (class II) HDACs in cultured neonatal rat cardiomyocytes. 17-β-Estradiol or estrogen receptor β agonists dipropylnitrile and β-LGND2 comparably suppressed angiotensin II–induced HDAC2 (class I) production, HDAC-activating phosphorylation, and the resulting prohypertrophic mRNA expression. In contrast, estrogenic compounds derepressed the opposite effects of angiotensin II on the same parameters for HDAC4 and 5 (class II), resulting in retention of these deacetylases in the nucleus to inhibit hypertrophic gene expression. Key aspects were confirmed in vivo from the hearts of wild-type but not estrogen receptor β (ERβ) gene–deleted mice administered angiotensin II and estrogenic compounds. Our results identify a novel dual regulation of cardiomyocyte HDACs, shown here for the antihypertrophic sex steroid acting at ERβ. This mechanism potentially supports using ERβ agonists as HDAC modulators to treat cardiac disease. PMID:24152730

The role of echocardiography in the evaluation of cardiac re-modelling and differentiation between physiological and pathological hypertrophy in teenagers engaged in competitive amateur sports.

PubMed

Sulovic, Ljiljana S; Mahmutovic, Meho; Lazic, Snezana; Sulovic, Nenad

2017-05-01

Aims "Athlete's heart" is a cardiac adaptation to long-term intensive training. The aims of this study were to show the prevalence of left ventricular hypertrophy in teenagers who participate in sports, to define the different types of cardiac re-modelling, and to differentiate between physiological and pathological hypertrophy. Echocardiographic measurements were obtained by M-mode, two dimensional, and Doppler techniques of participants from sports and control groups. The echocardiographic examinations included 100 healthy teenagers taking part in dynamic sports such as football and basketball and 100 healthy teenagers taking part in static sports such as karate and judo. The control group (n=100) included healthy, sedentary teenagers. Sports participants had significantly higher left ventricular mass when compared with the control group, (p0.05). Respondents from both groups had E/A ratios (transmitral flow velocity ratio)>1, preserved diastolic function, and statistically they did not differ from the control group. Echocardiographic parameters show that physiological hypertrophy and cardiac re-modelling are present in teenagers who play sports. Unexpectedly, the prevalence of concentric and eccentric types of re-modelling is equally possible in the group of static sports participants.

Spiral-wave dynamics in a mathematical model of human ventricular tissue with myocytes and fibroblasts.

PubMed

Nayak, Alok Ranjan; Shajahan, T K; Panfilov, A V; Pandit, Rahul

2013-01-01

Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as [Formula: see text], the fibroblast resting-membrane potential, the fibroblast conductance [Formula: see text], and the MF gap-junctional coupling [Formula: see text]. Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as [Formula: see text], and [Formula: see text], and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-wave conduction velocity [Formula: see text] decreases as a function of [Formula: see text], for zero-sided and one-sided couplings; however, for two-sided coupling, [Formula: see text] decreases initially and then increases as a function of [Formula: see text], and, eventually, we observe that conduction failure occurs for low values of [Formula: see text]. In our homogeneous studies, we find that the rotation speed and stability of a spiral wave can be controlled either by controlling [Formula: see text] or [Formula: see text]. Our studies with fibroblast inhomogeneities show that a spiral wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of spiral-wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities.

Cardiac and thermal homeostasis in the aging Brown Norway rat.

EPA Science Inventory

The Brown Norway (BN) rat is a popular strain for aging studies. There is little information on effects of age on baseline cardiac and thermoregulatory parameters in undisturbed BN rats even though cardiac and thermal homeostasis is linked to many pathological deficits in the age...

The Diagnostic Value of Pulsed Wave Tissue Doppler Imaging in Asymptomatic Beta- Thalassemia Major Children and Young Adults; Relation to Chemical Biomarkers of Left Ventricular Function and Iron Overload

PubMed Central

Ragab, Seham M; Fathy, Waleed M; El-Aziz, Walaa FAbd; Helal, Rasha T

2015-01-01

Background Cardiac iron toxicity is the leading cause of death among β-halassaemia major (TM) patients. Once heart failure becomes overt, it is difficult to reverse. Objectives To investigate non-overt cardiac dysfunctions in TM patients using pulsed wave Tissue Doppler Imaging (TD I) and its relation to iron overload and brain natriuretic peptide (BNP). Methods Thorough clinical, conventional echo and pulsed wave TDI parameters were compared between asymptomatic 25 β-TM patients and 20 age and gender matched individuals. Serum ferritin and plasma BNP levels were assayed by ELISA. Results TM patients had significant higher mitral inflow early diastolic (E) wave and non significant other conventional echo parameters. In the patient group, pulsed wave TDI revealed systolic dysfunctions, in the form of significant higher isovolumetric contraction time (ICT), and lower ejection time (E T), with diastolic dysfunction in the form of higher isovolumetric relaxation time (IRT), and lower mitral annulus early diastolic velocity E′ (12.07 ±2.06 vs 15.04±2.65, P= 0.003) compared to the controls. Plasma BNP was higher in patients compared to the controls. Plasma BNP and serum ferritin had a significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions. Patients with E/E′ ≥ 8 had significant higher serum ferritin and plasma BNP levels compared to those with ratio < 8 without a difference in Hb levels. Conclusion Pulsed wave TDI is an important diagnostic tool for latent cardiac dysfunction in iron-loaded TM patients and is related to iron overload and BNP. PMID:26401240

The Diagnostic Value of Pulsed Wave Tissue Doppler Imaging in Asymptomatic Beta- Thalassemia Major Children and Young Adults; Relation to Chemical Biomarkers of Left Ventricular Function and Iron Overload.

PubMed

Ragab, Seham M; Fathy, Waleed M; El-Aziz, Walaa FAbd; Helal, Rasha T

2015-01-01

Cardiac iron toxicity is the leading cause of death among β-halassaemia major (TM) patients. Once heart failure becomes overt, it is difficult to reverse. To investigate non-overt cardiac dysfunctions in TM patients using pulsed wave Tissue Doppler Imaging (TD I) and its relation to iron overload and brain natriuretic peptide (BNP). Thorough clinical, conventional echo and pulsed wave TDI parameters were compared between asymptomatic 25 β-TM patients and 20 age and gender matched individuals. Serum ferritin and plasma BNP levels were assayed by ELISA. TM patients had significant higher mitral inflow early diastolic (E) wave and non significant other conventional echo parameters. In the patient group, pulsed wave TDI revealed systolic dysfunctions, in the form of significant higher isovolumetric contraction time (ICT), and lower ejection time (E T), with diastolic dysfunction in the form of higher isovolumetric relaxation time (IRT), and lower mitral annulus early diastolic velocity E' (12.07 ±2.06 vs 15.04±2.65, P= 0.003) compared to the controls. Plasma BNP was higher in patients compared to the controls. Plasma BNP and serum ferritin had a significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions. Patients with E/E' ≥ 8 had significant higher serum ferritin and plasma BNP levels compared to those with ratio < 8 without a difference in Hb levels. Pulsed wave TDI is an important diagnostic tool for latent cardiac dysfunction in iron-loaded TM patients and is related to iron overload and BNP.

Female exposure to high G: echocardiographic evaluation for chronic changes in cardiac function.

PubMed

Albery, W B; Ten Eyck, R P; Wolfe, M

1998-09-01

Significant changes in cardiac preload and afterload are generated by a number of factors present during the operation of high performance aircraft. These include high levels of +Gz, positive pressure breathing and anti-G straining maneuvers. Centrifuge subjects are exposed to these same factors in doses that are comparable to their operational counterparts. The question of whether such exposures produce long-term adverse effects on the heart has not been definitively answered. In an effort to further address this issue, a longitudinal study was conducted on 18 newly recruited centrifuge panel members (7 males and 11 females) who did not have a previous history of significant high +Gz exposure. In order to document the cumulative long-term effects of high +Gz exposure and G protection measures, baseline echocardiographic studies were conducted prior to any +Gz exposure on the Dynamic Environment Simulator (DES) centrifuge. The echocardiograms were repeated after each panel member completed eight sessions of indoctrination. These follow-up echos were performed after all 18 subjects had been exposed to over 45 min (cumulative) of sustained acceleration > or = 2 G. Each subject served as his/her own control. All studies were evaluated independently by a cardiologist who was blinded to the order in which the studies were performed. Although complete echocardiographic studies were performed, only the parameters identified as significant in prior studies were evaluated. No significant differences were found between the initial and follow-up echo parameters. No significant differences were found between male and female responses. We found no significant differences in cardiac function after 45 min (cumulative) of exposure to G > or = 2 in men or women. These subjects will be monitored during a longitudinal study throughout their centrifuge subject career.

Combination of miRNA499 and miRNA133 Exerts a Synergic Effect on Cardiac Differentiation

PubMed Central

Pisano, Federica; Altomare, Claudia; Cervio, Elisabetta; Barile, Lucio; Rocchetti, Marcella; Ciuffreda, Maria Chiara; Malpasso, Giuseppe; Copes, Francesco; Mura, Manuela; Danieli, Patrizia; Viarengo, Gianluca; Zaza, Antonio; Gnecchi, Massimiliano

2015-01-01

Several studies have demonstrated that miRNA are involved in cardiac development, stem cell maintenance, and differentiation. In particular, it has been shown that miRNA133, miRNA1, and miRNA499 are involved in progenitor cell differentiation into cardiomyocytes. However, it is unknown whether different miRNA may act synergistically to improve cardiac differentiation. We used mouse P19 cells as a cardiogenic differentiation model. miRNA499, miRNA1, or miRNA133 were transiently over-expressed in P19 cells individually or in different combinations. The over-expression of miRNA499 alone increased the number of beating cells and the association of miRNA499 with miRNA133 exerted a synergistic effect, further increasing the number of beating cells. Real-time polymerase chain reaction showed that the combination of miRNA499 + 133 enhanced the expression of cardiac genes compared with controls. Western blot and immunocytochemistry for connexin43 and cardiac troponin T confirmed these findings. Importantly, caffeine responsiveness, a clear functional parameter of cardiac differentiation, was increased by miRNA499 in association with miRNA133 and was directly correlated with the activation of the cardiac troponin I isoform promoter. Cyclic contractions were reversibly abolished by extracellular calcium depletion, nifedipine, ryanodine, and IP3R blockade. Finally, we demonstrated that the use of miRNA499 + 133 induced cardiac differentiation even in the absence of dimethyl sulfoxide. Our results show that the areas spontaneously contracting possess electrophysiological and pharmacological characteristics compatible with true cardiac excitation-contraction coupling. The translational relevance of our findings was reinforced by the demonstration that the over-expression of miRNA499 and miRNA133 was also able to induce the differentiation of human mesenchymal stromal cells toward the cardiac lineage. Stem Cells 2015;33:1187–1199 PMID:25534971

HRV Influence During Renal Transplantation Procedure on Long-Term Mortality.

PubMed

Biernawska, J; Kotfis, K; Kaczmarczyk, M; Błaszczyk, W; Barnik, E; Żukowski, M

2016-06-01

The autonomic nervous system plays an important role in heart function regulation. One of the most acknowledged methods for noninvasive measurement of autonomic system activity is to determine heart rate variability (HRV). Reduced HRV parameters-heart rate rigidity/stiffness-are an independent prognostic factor of sudden cardiac death risk because of arrhythmia. Renal transplantation is an important factor in HRV changes because of hemodynamic and ion disturbances. The main purpose of this study was to determine the influence of HRV disturbances during renal transplantation procedures on long-term mortality in patients with chronic kidney disease. A prospective observation study was performed in the Department of Anesthesiology, Intensive Care, and Acute Poisoning, Pomeranian Medical University, Szczecin, Poland. There were 75 patients (mean age, 47 ± 12 years; 42 men) treated with renal transplantation between 2008 and 2010. Patients were monitored with electrocardiographic tracing with the use of 7 electrodes in position type B. The final stage of analysis was to determine the possible relationship between HRV parameters during the perioperative period and the number of deaths within a 5-year follow-up. HRV parameters during the perioperative period of renal transplantation and the number of deaths within a 5-year follow-up, measured by use of the Holter method, did not differ among patients in the studied population. HRV is a noninvasive and confirmed tool used for the evaluation of autonomic function and mortality risk in patients with end-stage renal disease. HRV parameters recorded in the perioperative period are not optimal stratification tools for estimating the risk of cardiac deaths in patients with end-stage renal disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Computational modeling for cardiac safety pharmacology analysis: Contribution of fibroblasts.

PubMed

Gao, Xin; Engel, Tyler; Carlson, Brian E; Wakatsuki, Tetsuro

2017-09-01

Drug-induced proarrhythmic potential is an important regulatory criterion in safety pharmacology. The application of in silico approaches to predict proarrhythmic potential of new compounds is under consideration as part of future guidelines. Current approaches simulate the electrophysiology of a single human adult ventricular cardiomyocyte. However, drug-induced proarrhythmic potential can be different when cardiomyocytes are surrounded by non-muscle cells. Incorporating fibroblasts in models of myocardium is important particularly for predicting a drugs cardiac liability in the aging population - a growing population who take more medications and exhibit increased cardiac fibrosis. In this study, we used computational models to investigate the effects of fibroblast coupling on the electrophysiology and response to drugs of cardiomyocytes. A computational model of cardiomyocyte electrophysiology and ion handling (O'Hara, Virag, Varro, & Rudy, 2011) is coupled to a passive model of fibroblast electrophysiology to test the effects of three compounds that block cardiomyocyte ion channels. Results are compared to model results without fibroblast coupling to see how fibroblasts affect cardiomyocyte action potential duration at 90% repolarization (APD 90 ) and propensity for early after depolarization (EAD). Simulation results show changes in cardiomyocyte APD 90 with increasing concentration of three drugs that affect cardiac function (dofetilide, vardenafil and nebivolol) when no fibroblasts are coupled to the cardiomyocyte. Coupling fibroblasts to cardiomyocytes markedly shortens APD 90 . Moreover, increasing the number of fibroblasts can augment the shortening effect. Coupling cardiomyocytes and fibroblasts are predicted to decrease proarrhythmic susceptibility under dofetilide, vardenafil and nebivolol block. However, this result is sensitive to parameters which define the electrophysiological function of the fibroblast. Fibroblast membrane capacitance and conductance (C FB and G FB ) have less of an effect on APD 90 than the fibroblast resting membrane potential (E FB ). This study suggests that in both theoretical models and experimental tissue constructs that represent cardiac tissue, both cardiomyocytes and non-muscle cells should be considered when testing cardiac pharmacological agents. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

PubMed

Lu, Yi; Zhao, Ming; Liu, Jin-Jun; He, Xi; Yu, Xiao-Jiang; Liu, Long-Zhu; Sun, Lei; Chen, Li-Na; Zang, Wei-Jin

2017-09-01

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Health-Related Quality of Life, Functional Status, and Cardiac Event-Free Survival in Patients With Heart Failure.

PubMed

Wu, Jia-Rong; Lennie, Terry A; Frazier, Susan K; Moser, Debra K

2016-01-01

Health-related quality of life (HRQOL), functional status, and cardiac event-free survival are outcomes used to assess the effectiveness of interventions in patients with heart failure (HF). However, the nature of the relationships among HRQOL, functional status, and cardiac event-free survival remains unclear. The purpose of this study is to examine the nature of the relationships among HRQOL, functional status, and cardiac event-free survival in patients with HF. This was a prospective, observational study of 313 patients with HF that was a secondary analysis from a registry. At baseline, patient demographic and clinical data were collected. Health-related quality of life was assessed using the Minnesota Living With Heart Failure Questionnaire and functional status was measured using the Duke Activity Status Index. Cardiac event-free survival data were obtained by patient interview, hospital database, and death certificate review. Multiple linear and Cox regressions were used to explore the relationships among HRQOL, functional status, and cardiac event-free survival while adjusting for demographic and clinical factors. Participants (n = 313) were men (69%), white (79%), and aged 62 ± 11 years. Mean left ventricular ejection fraction was 35% ± 14%. The mean HRQOL score of 32.3 ± 20.6 indicated poor HRQOL. The mean Duke Activity Status Index score of 16.2 ± 12.9 indicated poor functional status. Cardiac event-free survival was significantly worse in patients who had worse HRQOL or poorer functional status. Patients who had better functional status had better HRQOL (P < .001). Health-related quality of life was not a significant predictor of cardiac event-free survival after entering functional status in the model (P = .54), demonstrating that it was a mediator of the relationship between HRQOL and outcome. Functional status was a mediator between HRQOL and cardiac event-free survival. These data suggest that intervention studies to improve functional status are needed.

The Correlation of Skeletal and Cardiac Muscle Dysfunction in Duchenne Muscular Dystrophy.

PubMed

Posner, Andrew D; Soslow, Jonathan H; Burnette, W Bryan; Bian, Aihua; Shintani, Ayumi; Sawyer, Douglas B; Markham, Larry W

2016-01-01

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle and cardiac dysfunction. While skeletal muscle dysfunction precedes cardiomyopathy, the relationship between the progressive decline in skeletal and cardiac muscle function is unclear. This relationship is especially important given that the myocardial effects of many developing DMD therapies are largely unknown. Our objective was to assess the relationship between progression of skeletal muscle weakness and onset of cardiac dysfunction in DMD. A total of 77 DMD subjects treated at a single referral center were included. Demographic information, quantitative muscle testing (QMT), subjective muscle strength, cardiac function, and current and retrospective medications were collected. A Spearman rank correlation was used to evaluate for an association between subjective strength and fractional shortening. The effects of total QMT and arm QMT on fractional shortening were examined in generalized least square with and without adjustments for age, ambulatory status, and duration of corticosteroids and cardiac specific medications. We found a significant correlation between maintained subjective skeletal muscle arm and leg strength and maintained cardiac function as defined by fractional shortening (rho=0.47, p=0.004 and rho=0.48, p=0.003, respectively). We also found a significant association between QMT and fractional shortening among non-ambulatory DMD subjects (p=0.03), while this association was not significant in ambulatory subjects. Our findings allow us to conclude that in this population, there exists a significant relationship between skeletal muscle and cardiac function in non-ambulatory DMD patients. While this does not imply a causal relationship, a possible association between skeletal and cardiac muscle function suggests that researchers should carefully monitor cardiac function, even when the primary outcome measures are not cardiac in nature.

Nanotized PPARα Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3β-Mediated Mitochondrial Death Pathway.

PubMed

Rana, Santanu; Datta, Ritwik; Chaudhuri, Ratul Datta; Chatterjee, Emeli; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

2018-05-09

Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (PPARα). Thereby, we hypothesized that a cardiac-specific induction of PPARα might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPARα augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy. Nanotized PPARα overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of PPARα ameliorated pathological hypertrophy and improved cardiac function. Augmented PPARα in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPARα with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3β (GSK3β), which upregulated inactive phospho-GSK3β (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in PPARα-overexpressed hypertrophy groups restored mitochondrial structure and function both in vitro and in vivo. Cardiomyocyte-targeted overexpression of a protein of interest (PPARα) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted PPARα-overexpressed myocardium. PPARα-overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of PPARα during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac function, thereby, opening up a potential avenue for cardiac tissue engineering during hypertrophic cardiac pathophysiology.

Feasibility of a Single Contrast Bolus High-Pitch Pulmonary CT Angiography Protocol Followed by Low-Dose Retrospectively ECG-Gated Cardiac CT in Patients with Suspected Pulmonary Embolism.

PubMed

Schäfer, Julia Carmen; Haubenreisser, Holger; Meyer, Mathias; Grüttner, Joachim; Walter, Thomas; Borggrefe, Martin; Schoepf, Joseph U; Nance, John W; Schönberg, Stefan O; Henzler, Thomas

2018-06-01

 To prospectively evaluate the feasibility of single contrast bolus high-pitch CT pulmonary angiography (CTPA) subsequently followed by low-dose retrospectively ECG-gated cardiac CT (4D-cCT) in patients with suspected pulmonary embolism (PE) to accurately evaluate right ventricular (RV) function.  62 patients (33 female, age 65.1 ± 17.5 years) underwent high-pitch CTPA examination with 80cc of iodinated contrast material. 5 s after the end of the high-pitch CTPA study, a low-dose retrospectively ECG-gated cardiac CT examination was automatically started. The volume CT dose index (CTDI vol) and dose length product (DLP) were recorded in all patients and the effective dose was calculated. For the assessment of image quality, attenuation was measured as Hounsfield units (HUs) within various regions of interest (ROIs). These ROIs were used to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality was assessed using a five-point Likert scale. On 4D-cCT, the ejection fraction of both ventricles (RVEF, LVEF) as well as the ratio of RVEF and LVEF (RVEF/LVEF) was assessed. The statistical difference of all parameters between the PE and non-PE group was calculated.  The mean effective radiation dose was 4.22 ± 2.05 mSv. Attenuation measurements on CTPA showed the highest attenuation values in the main pulmonary artery (442.01 ± 187.64). On 4D-cCT attenuation values were highest in the descending aorta (560.59 ± 208.81). The CNR and SNR values on CTPA were highest within the main pulmonary artery (CNR = 12.43 ± 4.57; SNR = 15.14 ± 4.90). On 4D-cCT images, the highest SNR and CNR could be measured in the descending aorta (CNR = 10.26 ± 5.57; SNR = 10.86 ± 5.17). The mean LVEF was 60.73 %± 14.65 %, and the mean RVEF was 44.90 %± 9.54 %. The mean RVEF/LVEF was 0.79 ± 0.29. There was no significant difference between the PE and non-PE group for either of the parameters.  The investigated combined CTPA and 4D-cCT protocol is feasible using a single contrast bolus and allows the evaluation of RV function in patients with suspected PE. Further studies have to evaluate the additional value of this protocol regarding risk stratification in patients with PE.   · High-pitch CTPA is fast enough to leave sufficient contrast material within the heart that can be used for an additional low-dose functional cardiac CT examination.. · The tube current of the evaluated 4D-cCT is reduced over the entire cardiac cycle without any full dose peak.. · Low-dose cardiac CT subsequently performed after high-pitch CTPA allows for detailed analysis of RV function.. · Schäfer JC, Haubenreisser H, Meyer M et al. Feasibility of a Single Contrast Bolus High-Pitch Pulmonary CT Angiography Protocol Followed by Low-Dose Retrospectively ECG-Gated Cardiac CT in Patients with Suspected Pulmonary Embolism. Fortschr Röntgenstr 2018; 190: 542 - 550. © Georg Thieme Verlag KG Stuttgart · New York.

[Telemetry in the clinical setting].

PubMed

Hilbel, Thomas; Helms, Thomas M; Mikus, Gerd; Katus, Hugo A; Zugck, Christian

2008-09-01

Telemetric cardiac monitoring was invented in 1949 by Norman J Holter. Its clinical use started in the early 1960s. In the hospital, biotelemetry allows early mobilization of patients with cardiovascular risk and addresses the need for arrhythmia or oxygen saturation monitoring. Nowadays telemetry either uses vendor-specific UHF band broadcasting or the digital ISM band (Industrial, Scientific, and Medical Band) standardized Wi-Fi network technology. Modern telemetry radio transmitters can measure and send multiple physiological parameters like multi-channel ECG, NIPB and oxygen saturation. The continuous measurement of oxygen saturation is mandatory for the remote monitoring of patients with cardiac pacemakers. Real 12-lead ECG systems with diagnostic quality are an advantage for monitoring patients with chest pain syndromes or in drug testing wards. Modern systems are light-weight and deliver a maximum of carrying comfort due to optimized cable design. Important for the system selection is a sophisticated detection algorithm with a maximum reduction of artifacts. Home-monitoring of implantable cardiac devices with telemetric functionalities are becoming popular because it allows remote diagnosis of proper device functionality and also optimization of the device settings. Continuous real-time monitoring at home for patients with chronic disease may be possible in the future using Digital Video Broadcasting Terrestrial (DVB-T) technology in Europe, but is currently not yet available.

Assessment of Fetal Myocardial Performance Index in Women with Placenta Previa.

PubMed

Zhang, Na; Sun, Lijuan; Zhang, Lina; Li, Zhen; Han, Jijing; Wu, Qingqing

2017-12-15

BACKGROUND This study investigated whether fetuses of placenta previa pregnancies have cardiac dysfunction by use of a modified myocardial performance index (Mod-MPI). MATERIAL AND METHODS A prospective cross-sectional study was conducted including 178 fetuses at 28-40 weeks of gestation. Eighty-nine fetuses of mothers with placenta previa and without pregnancy complications were recruited (placenta previa group) and matched with 89 fetuses of mothers with normal pregnancies (control group). Fetal cardiac function parameters and perinatal outcomes as well as the Mod-MPI were compared between the 2 groups. RESULTS The median Mod-MPI was significantly increased in fetuses of mothers with placenta previa compared with controls (0.47±0.05 vs. 0.45±0.05; P<0.01). Among fetuses of mothers with or without placenta previa, the Mod-MPI was significantly higher in the incomplete placenta previa group compared with the complete placenta previa group and control group (P<0.01). An increased Mod-MPI in placenta previa pregnancies was independently associated with fetal cord pH <7.2 (odds ratio, 4.8; 95% confidence interval, 0.98-23.54; P=0.003). CONCLUSIONS There is impairment of fetal cardiac function in pregnancies with placenta previa. An increased MPI was independently associated with adverse perinatal outcomes to some extent in the placenta previa pregnancies.

Gain-of-function mutant of angiotensin II receptor, type 1A, causes hypertension and cardiovascular fibrosis in mice

PubMed Central

Billet, Sandrine; Bardin, Sabine; Verp, Sonia; Baudrie, Véronique; Michaud, Annie; Conchon, Sophie; Muffat-Joly, Martine; Escoubet, Brigitte; Souil, Evelyne; Hamard, Ghislaine; Bernstein, Kenneth E.; Gasc, Jean Marie; Elghozi, Jean-Luc; Corvol, Pierre; Clauser, Eric

2007-01-01

The role of the renin-angiotensin system has been investigated by overexpression or inactivation of its different genes in animals. However, there is no data concerning the effect of the constitutive activation of any component of the system. A knockin mouse model has been constructed with a gain-of-function mutant of the Ang II receptor, type 1A (AT1A), associating a constitutively activating mutation (N111S) with a C-terminal deletion, which impairs receptor internalization and desensitization. In vivo consequences of this mutant receptor expression in homozygous mice recapitulate its in vitro characteristics: the pressor response is more sensitive to Ang II and longer lasting. These mice present with a moderate (~20 mmHg) and stable increase in BP. They also develop early and progressive renal fibrosis and cardiac fibrosis and diastolic dysfunction. However, there was no overt cardiac hypertrophy. The hormonal parameters (low-renin and inappropriately normal aldosterone productions) mimic those of low-renin human hypertension. This new model reveals that a constitutive activation of AT1A leads to cardiac and renal fibrosis in spite of a modest effect on BP and will be useful for investigating the role of Ang II in target organs in a model similar to some forms of human hypertension. PMID:17607364

Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions

NASA Technical Reports Server (NTRS)

Rice, John Jeremy; Stolovitzky, Gustavo; Tu, Yuhai; de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

2003-01-01

We have developed a model of cardiac thin filament activation using an Ising model approach from equilibrium statistical physics. This model explicitly represents nearest-neighbor interactions between 26 troponin/tropomyosin units along a one-dimensional array that represents the cardiac thin filament. With transition rates chosen to match experimental data, the results show that the resulting force-pCa (F-pCa) relations are similar to Hill functions with asymmetries, as seen in experimental data. Specifically, Hill plots showing (log(F/(1-F)) vs. log [Ca]) reveal a steeper slope below the half activation point (Ca(50)) compared with above. Parameter variation studies show interplay of parameters that affect the apparent cooperativity and asymmetry in the F-pCa relations. The model also predicts that Ca binding is uncooperative for low [Ca], becomes steeper near Ca(50), and becomes uncooperative again at higher [Ca]. The steepness near Ca(50) mirrors the steep F-pCa as a result of thermodynamic considerations. The model also predicts that the correlation between troponin/tropomyosin units along the one-dimensional array quickly decays at high and low [Ca], but near Ca(50), high correlation occurs across the whole array. This work provides a simple model that can account for the steepness and shape of F-pCa relations that other models fail to reproduce.

Effects of weightlessness on human baroreflex function

NASA Technical Reports Server (NTRS)

Fritsch, Janice M.; Eckberg, Dwain L.

1992-01-01

Impaired cardiovascular function, characterized by orthostatic intolerance and reduced exercise capacity, is a result of space travel. We hypothesized that postflight baroreflex dysfunction may contribute. We studied the vagally mediated carotid baroreceptor-cardiac reflex response of 6 astronauts before, during, and after the ten day SLS-l mission. A series of R-waves triggered pressure and suction steps (from 40 to minus 65 mmHg) were delivered to a neck chamber during held expirtation. Resulting R-R interval changes were plotted against carotid distending pressure (systolic - neck pressure), and curve parameters calculated. After an initial rise, the operational point declined consistently during the flight and reached a nadir on landing day, but had recovered to preflight levels by L + 4. Slope and range of the response declined throughout the flight, were slightly recovered by the time measurements were made on landing day, but still were reduced on L + 4. These data indicate that space flight results in a significant impairment of the carotid baroreceptor cardiac reflex response.

Effects of Trichothecenes on Cardiac Cell Electrical Function

DTIC Science & Technology

1985-12-13

Figure 8 illustrate the typical effects of trichothecene mycotoxins in canine ventricular cells. T-2 tetraol, for example, reduced the total duration of...potentials from false tendon cells and ventricular muscle cells (shown in Figure 8) illustrate the typical effects of trichothecene mycotoxins in canine...the plateau (arrow) from 14 my to 4 my. Table 6 summarizes the effects of T-2 mycotoxin on the action potential parameters of false tendon cells and

Restoration of Cardiac Tissue Thyroid Hormone Status in Experimental Hypothyroidism: A Dose-Response Study in Female Rats

PubMed Central

Weltman, Nathan Y.; Ojamaa, Kaie; Savinova, Olga V.; Chen, Yue-Feng; Schlenker, Evelyn H.; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Pol, Christine J.

2013-01-01

Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine whether the administration of T3 (instead of T4) improves the relationship between THs in serum and cardiac tissue and cardiac function over a short-term treatment period. Adult female Sprague Dawley rats were made hypothyroid by 7 weeks treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU). After establishing hypothyroidism, rats were assigned to 1 of 5 graded T3 dosages plus PTU for a 2-week dose-response experiment. Untreated, age-matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T3 and T4 levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene reexpression, and cardiac dysfunction. Short-term administration of T3 led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T3 levels was not associated with restoration of cardiac tissue T3 levels or cardiac function. In fact, a 3-fold higher T3 dosage was necessary to normalize cardiac tissue T3 levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states. PMID:23594789

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

PubMed

Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

2015-11-15

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function

PubMed Central

Rajendran, Pradeep S.; Nier, Heath A.; KenKnight, Bruce H.; Armour, J. Andrew

2015-01-01

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID:26371171

Reference ranges of left ventricular structure and function assessed by contrast-enhanced cardiac MR and changes related to ageing and hypertension in a population-based study.

PubMed

Bülow, Robin; Ittermann, Till; Dörr, Marcus; Poesch, Axel; Langner, Sönke; Völzke, Henry; Hosten, Norbert; Dewey, Marc

2018-03-14

Reference ranges of left ventricular (LV) parameters from cardiac magnetic resonance (CMR) were established to investigate the impact of ageing and hypertension as important determinants of cardiac structure and function. One thousand five hundred twenty-five contrast-enhanced CMRs were conducted in the Study of Health in Pomerania. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), ejection fraction (LVEF), and myocardial mass (LVMM) were determined using long- and short-axis steady-state free-precession sequences. The reference population was defined as participants without late enhancement, hypertension, and prior cardiovascular diseases. Reference ranges were established by quantile regression (5th and 95th percentile) and compared with an additional sample of treated and untreated hypertensives. LV volumes in the reference population (n = 634, 300 males, 334 females, 52.1 ± 13.3 years) aged between 20-69 years were lower with higher age (p = 0.001), whereas LVEFs were higher (p ≤ 0.020). LVMM was lower only in males (p = 0.002). Compared with the reference population, hypertension was associated with lower LVEDV in males (n = 258, p ≤ 0.032). Antihypertensive therapy was associated with higher LVEF in males (n = 258, +2.5%, p = 0.002) and females (n = 180, +2.1%, p = 0.001). Population-based LV reference ranges were derived from contrast-enhanced CMR. Hypertension-related changes were identified by comparing these values with those of hypertensives, and they might be used to monitor cardiac function in these patients. • Left ventricular function changed slightly but significantly between 20-69 years. • Reference values of BSA-indexed myocardial mass decreased with age in males. • Hypertension was associated with lower LV end-diastolic volume only in males. • CMR may allow assessing remodelling related to hypertension or antihypertensive treatment.

EFFECTS OF INDUCED RESPIRATORY CHANGES ON CARDIAC, VENTILATORY, AND THERMOREGULATORY PARAMETERS IN HEALTHY SPRAGUE-DAWLEY RATS

EPA Science Inventory

EFFECTS OF INDUCED RESPIRATORY CHANGES ON CARDIAC, VENTILATORY, AND THERMOREGULATORY PARAMETERS IN HEALTHY SPRAGUE-DAWLEY RATS. LB Wichers1, WH Rowan2, DL Costa2, MJ Campen3 and WP Watkinson2 1UNC SPH, Chapel Hill, NC, USA; 2USEPA, ORD/NHEERL/ETD/PTB, RTP, NC, USA; 3LRRI, A...

EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH (ROFA) ON CARDIAC, PULMONARY, AND THERMOREGULATORY PARAMETERS IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS

EPA Science Inventory

EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH (ROFA) ON CARDIAC, PULMONARY, AND THERMOREGULATORY PARAMETERS IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. LB Wichers1, JP Nolan2, DW Winsett2, AD Ledbetter2, UP Kodavanti2, MCJ Schladweiler2, R Hauser3, DC Christiani3, DL Costa2, ...

A time dependent anatomically detailed model of cardiac conduction

NASA Technical Reports Server (NTRS)

Saxberg, B. E.; Grumbach, M. P.; Cohen, R. J.

1985-01-01

In order to understand the determinants of transitions in cardiac electrical activity from normal patterns to dysrhythmias such as ventricular fibrillation, we are constructing an anatomically and physiologically detailed finite element simulation of myocardial electrical propagation. A healthy human heart embedded in paraffin was sectioned to provide a detailed anatomical substrate for model calculations. The simulation of propagation includes anisotropy in conduction velocity due to fiber orientation as well as gradients in conduction velocities, absolute and relative refractory periods, action potential duration and electrotonic influence of nearest neighbors. The model also includes changes in the behaviour of myocardial tissue as a function of the past local activity. With this model, we can examine the significance of fiber orientation and time dependence of local propagation parameters on dysrhythmogenesis.

Multiscale Characterization of Engineered Cardiac Tissue Architecture.

PubMed

Drew, Nancy K; Johnsen, Nicholas E; Core, Jason Q; Grosberg, Anna

2016-11-01

In a properly contracting cardiac muscle, many different subcellular structures are organized into an intricate architecture. While it has been observed that this organization is altered in pathological conditions, the relationship between length-scales and architecture has not been properly explored. In this work, we utilize a variety of architecture metrics to quantify organization and consistency of single structures over multiple scales, from subcellular to tissue scale as well as correlation of organization of multiple structures. Specifically, as the best way to characterize cardiac tissues, we chose the orientational and co-orientational order parameters (COOPs). Similarly, neonatal rat ventricular myocytes were selected for their consistent architectural behavior. The engineered cells and tissues were stained for four architectural structures: actin, tubulin, sarcomeric z-lines, and nuclei. We applied the orientational metrics to cardiac cells of various shapes, isotropic cardiac tissues, and anisotropic globally aligned tissues. With these novel tools, we discovered: (1) the relationship between cellular shape and consistency of self-assembly; (2) the length-scales at which unguided tissues self-organize; and (3) the correlation or lack thereof between organization of actin fibrils, sarcomeric z-lines, tubulin fibrils, and nuclei. All of these together elucidate some of the current mysteries in the relationship between force production and architecture, while raising more questions about the effect of guidance cues on self-assembly function. These types of metrics are the future of quantitative tissue engineering in cardiovascular biomechanics.

A portable cadmium telluride multidetector probe for cardiac function monitoring

NASA Astrophysics Data System (ADS)

Arntz, Y.; Chambron, J.; Dumitresco, B.; Eclancher, B.; Prat, V.

1999-06-01

A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5×5×2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) which well depicted the filling and ejection of the cardiac beats, allowing to compare the clinically relevant parameters of the cardiac performance, proportional variables of the stroke volume (SV), ejection fraction (EF) and ventricular flow-rate with the known absolute values programmed on the model. The portable system is now in operation for clinical assessment of cardiac patients.

PubMed Central

Russo, Vincenzo; Papa, Andrea Antonio; Rago, Anna; D'Ambrosio, Paola; Cimmino, Giovanni; Palladino, Alberto; Nigro, Gerardo

2016-01-01

Sudden cardiac death in myotonic dystrophy type I (DM1) patients can be attributed to atrioventricular blocks as far as to the development of life-threatening arrhythmias which occur even in hearts with normal left ventricular systolic and diastolic function. Heterogeneity of ventricular repolarization is considered to provide an electrophysiological substrate for malignant arrhythmias. QTc dispersion (QTc-D), JTc dispersion (JTc-D) and transmural dispersion of repolarization (TDR) could reflect the physiological variability of regional and transmural ventricular repolarization. Aim of the present study was to investigate the heterogeneity of ventricular repolarization in patients with DM1 and preserved diastolic and systolic cardiac function. The study enrolled 50 DM1 patients (mean age 44 ± 5 years; M:F: 29:21) with preserved systolic and diastolic function of left ventricle among 247 DM1 patients followed at Cardiomyology and Medical Genetics of Second University of Naples, and 50 sexand age-matched healthy controls. The electrocardiographic parameters investigated were the following: Heart Rate, QRS duration, maximum and minimum QT and JT intervals, QTc- D, JTc-D and TDR. Compared to the controls, the DM1 group presented increased values of QTc-D (86.7 ± 40.1 vs 52.3 ± 11.9 ms; p = 0.03), JTc-D (78.6 ± 31.3 vs 61.3 ± 10.2 ms; p = 0.001) and TDR (101.6 ± 18.06 vs 90.1 ± 14.3 ms; p = 0.004) suggesting a significant increase in regional and transmural heterogeneity of the ventricular repolarization in these patients, despite a preserved systolic and diastolic cardiac function. PMID:28344440

High-sensitive cardiac Troponin T is superior to echocardiography in predicting 1-year mortality in patients with SIRS and shock in intensive care.

PubMed

Bergenzaun, Lill; Ohlin, Hans; Gudmundsson, Petri; Düring, Joachim; Willenheimer, Ronnie; Chew, Michelle S

2012-09-24

Left ventricular (LV) dysfunction is well documented in the critically ill. We assessed 1-year mortality in relation to cardiac biomarkers and LV function parameters by echocardiography in patients with shock. A prospective, observational, cohort study of 49 patients. B-natriuretic peptide (BNP), high-sensitive troponin T (hsTNT) and transthoracic echocardiography (TTE) were assessed within 12 h of study inclusion. LV systolic function was measured by ejection fraction (LVEF), mean atrioventricular plane displacement (AVPDm), peak systolic tissue Doppler velocity imaging (TDIs) and velocity time integral in the LV outflow tract (LVOT VTI). LV diastolic function was evaluated by transmitral pulsed Doppler (E, A, E/A, E-deceleration time), tissue Doppler indices (é, á, E/é) and left atrial volume (La volume). APACHE II (Acute Physiology and Chronic Health Evaluation) and SOFA (Sequential Organ Failure Assessment) scores were calculated. hsTNT was significantly higher in non-survivors than in survivors (60 [17.0-99.5] vs 168 [89.8-358] ng/l, p = 0.003). Other univariate predictors of mortality were APACHE II (p = 0.009), E/é (p = 0.023), SOFA (p = 0.024) and age (p = 0.031). Survivors and non-survivors did not differ regarding BNP (p = 0.26) or any LV systolic function parameter (LVEF p = 0.87, AVPDm p = 0.087, TDIs p = 0.93, LVOT VTI p = 0.18). Multivariable logistic regression analysis identified hsTNT (p = 0.010) as the only independent predictor of 1-year mortality; adjusted odds ratio 2.0 (95% CI 1.2- 3.5). hsTNT was the only independent predictor of 1-year mortality in patients with shock. Neither BNP nor echocardiographic parameters had an independent prognostic value. Further studies are needed to establish the clinical significance of elevated hsTNT in patients in shock.

Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT.

PubMed

Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia; Fanti, Stefano; Sambuceti, Gianmario

2015-11-01

Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III-IV) after CRT using (11)C-hydroxyephedrine (HED) PET/CT. Ten IHF patients (mean age = 68; range = 55-81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with "impaired innervation" (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation. This work might contribute to identify imaging parameters that could predict the response to CRT therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A)

PubMed Central

Lin, Hsiang-Yu; Liu, Hao-Chuan; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Hsu, Ting-Rong; Shen, Chia-I; Li, Shao-Tzu; Li, Cheng-Fang; Lee, Li-Hong; Lee, Pi-Chang; Huang, Chun-Kai; Chiang, Chuan-Chi; Lin, Ching-Yuang; Lin, Shuan-Pei; Niu, Dau-Ming

2013-01-01

Objective Current studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A). Design Retrospective cohort study. Setting Tertiary medical centre. Participants 21 patients with cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with classic Fabry disease (4 men and 11 women) treated with biweekly intravenous infusions of agalsidase β (1 mg/kg) or agalsidase α (0.2 mg/kg) for at least 6 months. Outcome measures These data were collected at the time before enzyme replacement therapy (ERT) began and followed up after ERT for at least 6 months, including patient demographics, medical history, parameter changes of cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3) and Mainz Severity Score Index. Results After 6–39 months of ERT, plasma lyso-Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with cardiac-type and classic Fabry disease, respectively, which indicated an improvement of disease severity. For patients with cardiac-type Fabry disease, echocardiography revealed the reduction or stabilisation of left ventricular mass index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively, as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type. Most patients showed stable renal function after ERT. There were statistically significant improvements (p<0.05) between the data at baseline and those after ERT for values of plasma lyso-Gb3, LVMI, IVS, LPW and Mainz Severity Score Index. No severe clinical events were reported during the treatment. Conclusions ERT is beneficial and appears to be safe for Taiwanese patients with cardiac-type Fabry disease, as well as for those with the classic type. PMID:23864212

Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid.

PubMed

Li, Chun-jun; Lv, Lin; Li, Hui; Yu, De-min

2012-06-19

Alpha-lipoic acid (ALA), a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM) has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS), extracellular matrix (ECM) remodeling and interrelated signaling pathways in a diabetic rat model. Diabetes was induced in rats by I.V. injection of streptozotocin (STZ) at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen) was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2) levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β). Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK), p38 MAPK and ERK were also assayed by Western blot. DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated signaling pathway components were evaluated. It was shown that redox homeostasis was disturbed and MAPK signaling pathway components activated in STZ-induced DCM animals. While ALA treatment favorably shifted redox homeostasis and suppressed JNK and p38 MAPK activation. These results, coupled with the excellent safety and tolerability profile of ALA in humans, demonstrate that ALA may have therapeutic potential in the treatment of DCM by attenuating MOS, ECM remodeling and JNK, p38 MAPK activation.

3D bioprinted functional and contractile cardiac tissue constructs

PubMed Central

Wang, Zhan; Lee, Sang Jin; Cheng, Heng-Jie; Yoo, James J.; Atala, Anthony

2018-01-01

Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However, its applications remain limited because the cardiac tissue is a highly organized structure with unique physiologic, biomechanical, and electrical properties. In this study, we undertook a proof-of-concept study to develop a contractile cardiac tissue with cellular organization, uniformity, and scalability by using three-dimensional (3D) bioprinting strategy. Primary cardiomyocytes were isolated from infant rat hearts and suspended in a fibrin-based bioink to determine the priting capability for cardiac tissue engineering. This cell-laden hydrogel was sequentially printed with a sacrificial hydrogel and a supporting polymeric frame through a 300-μm nozzle by pressured air. Bioprinted cardiac tissue constructs had a spontaneous synchronous contraction in culture, implying in vitro cardiac tissue development and maturation. Progressive cardiac tissue development was confirmed by immunostaining for α-actinin and connexin 43, indicating that cardiac tissues were formed with uniformly aligned, dense, and electromechanically coupled cardiac cells. These constructs exhibited physiologic responses to known cardiac drugs regarding beating frequency and contraction forces. In addition, Notch signaling blockade significantly accelerated development and maturation of bioprinted cardiac tissues. Our results demonstrated the feasibility of bioprinting functional cardiac tissues that could be used for tissue engineering applications and pharmaceutical purposes. PMID:29452273

Functional Aortic Root Parameters and Expression of Aortopathy in Bicuspid Versus Tricuspid Aortic Valve Stenosis.

PubMed

Girdauskas, Evaldas; Rouman, Mina; Disha, Kushtrim; Fey, Beatrix; Dubslaff, Georg; Theis, Bernhard; Petersen, Iver; Gutberlet, Matthias; Borger, Michael A; Kuntze, Thomas

2016-04-19

The correlation between bicuspid aortic valve (BAV) disease and aortopathy is not fully defined. This study aimed to prospectively analyze the correlation between functional parameters of the aortic root and expression of aortopathy in patients undergoing surgery for BAV versus tricuspid aortic valve (TAV) stenosis. From January 1, 2012 through December 31, 2014, 190 consecutive patients (63 ± 8 years, 67% male) underwent aortic valve replacement ± proximal aortic surgery for BAV stenosis (n = 137, BAV group) and TAV stenosis (n = 53, TAV group). All patients underwent pre-operative cardiac magnetic resonance imaging to evaluate morphological/functional parameters of the aortic root. Aortic tissue was sampled during surgery on the basis of the location of eccentric blood flow contact with the aortic wall, as determined by cardiac magnetic resonance (i.e., jet sample and control sample). Aortic wall lesions were graded using a histological sum score (0 to 21). The largest cross-sectional aortic diameters were at the mid-ascending level in both groups and were larger in BAV patients (40.2 ± 7.2 mm vs. 36.6 ± 3.3 mm, respectively, p < 0.001). The histological sum score was 2.9 ± 1.4 in the BAV group versus 3.4 ± 2.6 in the TAV group (p = 0.4). The correlation was linear and comparable between the maximum indexed aortic diameter and the angle between the left ventricular outflow axis and aortic root (left ventricle/aorta angle) in both groups (BAV group: r = 0.6, p < 0.001 vs. TAV group r = 0.45, p = 0.03, z = 1.26, p = 0.2). Logistic regression identified the left ventricle/aorta angle as an indicator of indexed aortic diameter >22 mm/m(2) (odds ratio: 1.2; p < 0.001). Comparable correlation patterns between functional aortic root parameters and expression of aortopathy are found in patients with BAV versus TAV stenosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Differential and Conditional Activation of PKC-Isoforms Dictates Cardiac Adaptation during Physiological to Pathological Hypertrophy

PubMed Central

Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha

2014-01-01

A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID:25116170

The effect of time to defibrillation and targeted temperature management on functional survival after out-of-hospital cardiac arrest.

PubMed

Drennan, Ian R; Lin, Steve; Thorpe, Kevin E; Morrison, Laurie J

2014-11-01

Cardiac arrest physiology has been proposed to occur in three distinct phases: electrical, circulatory and metabolic. There is limited research evaluating the relationship of the 3-phase model of cardiac arrest to functional survival at hospital discharge. Furthermore, the effect of post-cardiac arrest targeted temperature management (TTM) on functional survival during each phase is unknown. To determine the effect of TTM on the relationship between the time of initial defibrillation during each phase of cardiac arrest and functional survival at hospital discharge. This was a retrospective observational study of consecutive adult (≥18 years) out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythms. Included patients obtained a return of spontaneous circulation (ROSC) and were eligible for TTM. Multivariable logistic regression was used to determine predictors of functional survival at hospital discharge. There were 20,165 OHCA treated by EMS and 871 patients were eligible for TTM. Of these patients, 622 (71.4%) survived to hospital discharge and 487 (55.9%) had good functional survival. Good functional survival was associated with younger age (OR 0.94; 95% CI 0.93-0.95), shorter times from collapse to initial defibrillation (OR 0.73; 95% CI 0.65-0.82), and use of post-cardiac arrest TTM (OR 1.49; 95% CI 1.07-2.30). Functional survival decreased during each phase of the model (65.3% vs. 61.7% vs. 50.2%, P<0.001). Functional survival at hospital discharge was associated with shorter times to initial defibrillation and was decreased during each successive phase of the 3-phase model. Post-cardiac arrest TTM was associated with improved functional survival. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis

PubMed Central

Haller, Steven T.; Fan, Xiaoming; Xie, Jeffrey X.; Kennedy, David J.; Liu, Jiang; Yan, Yanling; Hernandez, Dawn-Alita; Mathew, Denzil P.; Cooper, Christopher J.; Shapiro, Joseph I.; Tian, Jiang

2016-01-01

Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0.05) decreased renal and cardiac expression of the antifibrotic microRNA miR-29b-3 and increased expression of molecular fibrosis markers. In terms of cardiac and renal organ structure and function, exposure to cigarette smoke led to significantly increased systolic blood pressure, cardiac hypertrophy, cardiac and renal fibrosis, and decreased renal function. These data indicate that decreased expression of miR-29b-3p is a novel mechanism wherein cigarette smoke promotes accelerated cardiac and renal tissue injury in CKD. (155 words) PMID:27789733

Quantitative computed tomography of pulmonary emphysema and ventricular function in chronic obstructive pulmonary disease patients with pulmonary hypertension.

PubMed

Huang, Yu-Sen; Hsu, Hsao-Hsun; Chen, Jo-Yu; Tai, Mei-Hwa; Jaw, Fu-Shan; Chang, Yeun-Chung

2014-01-01

This study strived to evaluate the relationship between degree of pulmonary emphysema and cardiac ventricular function in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) using electrocardiographic-gated multidetector computed tomography (CT). Lung transplantation candidates with the diagnosis of COPD and PH were chosen for the study population, and a total of 15 patients were included. The extent of emphysema is defined as the percentage of voxels below -910 Hounsfield units in the lung windows in whole lung CT without intravenous contrast. Heart function parameters were measured by electrocardiographic-gated CT angiography. Linear regression analysis was conducted to examine the associations between percent emphysema and heart function indicators. Significant correlations were found between percent emphysema and right ventricular (RV) measurements, including RV end-diastolic volume (R(2) = 0.340, p = 0.023), RV stroke volume (R(2) = 0.406, p = 0.011), and RV cardiac output (R(2) = 0.382, p = 0.014); the correlations between percent emphysema and left ventricular function indicators were not observed. The study revealed that percent emphysema is correlated with RV dysfunction among COPD patients with PH. Based on our findings, percent emphysema can be considered for use as an indicator to predict the severity of right ventricular dysfunction among COPD patients.

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

PubMed

Gori, Mauro; Senni, Michele; Gupta, Deepak K; Charytan, David M; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M; Santos, Angela B S; Zile, Michael R; Voors, Adriaan A; McMurray, John J V; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D

2014-12-21

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Cardiac troponin I for the prediction of functional recovery and left ventricular remodelling following primary percutaneous coronary intervention for ST-elevation myocardial infarction.

PubMed

Hallén, Jonas; Jensen, Jesper K; Fagerland, Morten W; Jaffe, Allan S; Atar, Dan

2010-12-01

To investigate the ability of cardiac troponin I (cTnI) to predict functional recovery and left ventricular remodelling following primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI). Post hoc study extending from randomised controlled trial. 132 patients with STEMI receiving pPCI. Left ventricular ejection fraction (LVEF), end-diastolic and end-systolic volume index (EDVI and ESVI) and changes in these parameters from day 5 to 4 months after the index event. Cardiac magnetic resonance examination performed at 5 days and 4 months for evaluation of LVEF, EDVI and ESVI. cTnI was sampled at 24 and 48 h. In linear regression models adjusted for early (5 days) assessment of LVEF, ESVI and EDVI, single-point cTnI at either 24 or 48 h were independent and strong predictors of changes in LVEF (p<0.01), EDVI (p<0.01) and ESVI (p<0.01) during the follow-up period. In a logistic regression analysis for prediction of an LVEF below 40% at 4 months, single-point cTnI significantly improved the prognostic strength of the model (area under the curve = 0.94, p<0.01) in comparison with the combination of clinical variables and LVEF at 5 days. Single-point sampling of cTnI after pPCI for STEMI provides important prognostic information on the time-dependent evolution of left ventricular function and volumes.

Impact of sickle cell anaemia on cardiac chamber size in the paediatric population.

PubMed

Adjagba, Philippe M; Habib, Gaston; Robitaille, Nancy; Pastore, Yves; Raboisson, Marie-Josée; Curnier, Daniel; Dahdah, Nagib

2017-07-01

Purpose Sickle cell disease is known to cause various degrees of vasculopathy, including impact on heart function. The aims of this single-centre, retrospective study were to assess cardiac chamber size and function and the relationship with haematological indices such as haemoglobin, aspartate aminotransferase, reticulocytosis and bilirubin, lactate dehydrogenase in sickle cell disease. Right ventricle and left ventricle diastolic diameters, left ventricle mass estimate, left ventricle shortening fraction, myocardial performance index, and an index of myocardial relaxation (E/E') were calculated and correlated with haematological parameters. A total of 110 patients (65% haemoglobin SS, 29% haemoglobin SC) were studied at a mean age of 12.14±5.26 years. Right ventricle dilatation and left ventricle dilatation were present in 61.5 and 42.9%, respectively. Left ventricle mass was abnormal in 21.9%; all patients had normal myocardial performance index, 31.4% had abnormal E/E', and left ventricle shortening fraction was low in 38.1%. Cardiac dilatation was best correlated with haemoglobin, aspartate aminotransferase, reticulocytosis and bilirubin. Best subset regression analysis yielded significant additional prediction for right ventricle or left ventricle dilatation with haemoglobin, bilirubin, and lactate dehydrogenase. Abnormal E/E' was solely predictable with haemoglobin level. Hydroxyurea-treated patients had improved diastolic function. Right ventricle dilatation was more prevalent than left ventricle dilatation. The long-term consequences of right ventricular dilatation, clinical consequences, and association with pulmonary vasculopathy need to be further determined.

Hemoadsorption in cardiac shock with biventricular failure and giant-cell myocarditis: A case report.

PubMed

Dogan, Günes; Hanke, Jasmin; Puntigam, Jakob; Haverich, Axel; Schmitto, Jan D

2018-05-01

Giant-cell myocarditis represents a rare and often fatal autoimmune disorder. Despite extracorporeal life support being a valid treatment option, alternatives to control the underlying inflammatory response remain sparse. A new hemoadsorption device (CytoSorb) has recently been introduced to treat patients with an excessive inflammatory response. A 57-year-old patient developed fulminant right heart failure, respiratory insufficiency, hemodynamic instability, and oliguric-anuric renal failure. An extracorporeal life support together with an Impella was implanted for circulatory support. Due to non-pulsatility, acontractility of the left ventricle and a heavily reduced right ventricular function, a left ventricular assist device implantation and change from extracorporeal life support to veno-pulmonary arterial extracorporeal membrane oxygenation was performed. Since adequate hemodynamic stabilization could not be achieved and due to increasing inflammatory mediators and bilirubin levels, the decision was made to additionally integrate a CytoSorb hemoadsorber into the system. The combined treatment resulted in a clear and steady improvement in hemodynamics and the inflammatory condition with marked reductions in all measured parameters throughout the treatment period. Metabolic acidosis resolved and liver function improved. Extracorporeal life support therapy represents a bridging approach to heart transplantation or to cardiac recovery and can be complemented by CytoSorb as an independent therapeutic option. The patient described herein with giant-cell myocarditis and fulminant cardiac failure who received substantial extracorporeal support in combination with CytoSorb hemoadsorption therapy benefited in terms of an improvement of organ function and his inflammatory situation.

Comparative Effect of Levosimendan and Milrinone in Cardiac Surgery Patients With Pulmonary Hypertension and Left Ventricular Dysfunction.

PubMed

Mishra, Abhi; Kumar, Bhupesh; Dutta, Vikas; Arya, V K; Mishra, Anand Kumar

2016-06-01

To compare the effects of levosimendan with milrinone in cardiac surgical patients with pulmonary hypertension and left ventricular dysfunction. A prospective, randomized study. Tertiary care teaching hospital. The study included patients with valvular heart disease and pulmonary artery hypertension undergoing valve surgery. Forty patients were allocated randomly to receive either milrinone, 50 µg/kg bolus followed by infusion at a rate of 0.5 µg/kg/min (group 1), or levosimendan, 10 µg/kg bolus followed by infusion at a rate of 0.1 µg/kg/min (group 2) for 24 hours after surgery. Hemodynamic parameters were measured using a pulmonary artery catheter, and biventricular functions were assessed using echocardiography. Mean pulmonary artery pressures and the pulmonary vascular resistance index were comparable between the 2 groups at several time points in the intensive care unit. Biventricular function was comparable between both groups. Postcardiopulmonary bypass right ventricular systolic and diastolic functions decreased in both groups compared with baseline, whereas 6 hours postbypass left ventricular ejection fraction improved in patients with stenotic valvular lesions. Levosimendan use was associated with higher heart rate, increased cardiac index, decreased systemic vascular resistance index, and increased requirement of norepinephrine infusion compared with milrinone. The results of this study demonstrated that levosimendan was not clinically better than milrinone. Levosimendan therapy resulted in a greater increase in heart rate, decrease in systemic vascular resistance, and a greater need for norepinephrine than in patients who received milrinone. Copyright © 2016 Elsevier Inc. All rights reserved.

Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI.

PubMed

Barton, Gregory P; Vildberg, Lauren; Goss, Kara; Aggarwal, Niti; Eldridge, Marlowe; McMillan, Alan B

2018-05-01

Cardiac metabolic changes in heart disease precede overt contractile dysfunction. However, metabolism and function are not typically assessed together in clinical practice. The purpose of this study was to develop a cardiac positron emission tomography/magnetic resonance (PET/MR) stress test to assess the dynamic relationship between contractile function and metabolism in a preclinical model. Following an overnight fast, healthy pigs (45-50 kg) were anesthetized and mechanically ventilated. 18 F-fluorodeoxyglucose ( 18 F-FDG) solution was administered intravenously at a constant rate of 0.01 mL/s for 60 minutes. A cardiac PET/MR stress test was performed using normoxic gas (F I O 2  = .209) and hypoxic gas (F I O 2  = .12). Simultaneous cardiac imaging was performed on an integrated 3T PET/MR scanner. Hypoxic stress induced a significant increase in heart rate, cardiac output, left ventricular (LV) ejection fraction (EF), and peak torsion. There was a significant decline in arterial SpO 2 , LV end-diastolic and end-systolic volumes in hypoxia. Increased LV systolic function was coupled with an increase in myocardial FDG uptake (Ki) during hypoxic stress. PET/MR with continuous FDG infusion captures dynamic changes in both cardiac metabolism and contractile function. This technique warrants evaluation in human cardiac disease for assessment of subtle functional and metabolic abnormalities.

A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice.

PubMed

Carbone, Salvatore; Mauro, Adolfo G; Mezzaroma, Eleonora; Kraskauskas, Donatas; Marchetti, Carlo; Buzzetti, Raffaella; Van Tassell, Benjamin W; Abbate, Antonio; Toldo, Stefano

2015-11-01

Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, exercise intolerance and cardiac dysfunction. Unhealthy diet has been associated with increased risk of obesity and heart disease, but whether it directly affects cardiac function, and promotes the development and progression of HF is unknown. We fed 8-week old male or female CD-1 mice with a standard diet (SD) or a diet rich in saturated fat and sugar, resembling a "Western" diet (WD). Cardiac systolic and diastolic function was measured at baseline and 4 and 8 weeks by Doppler echocardiography, and left ventricular (LV) end-diastolic pressure (EDP) by cardiac catheterization prior to sacrifice. An additional group of mice received WD for 4 weeks followed by SD (wash-out) for 8 weeks. WD-fed mice experienced a significant decreased in LV ejection fraction (LVEF), reflecting impaired systolic function, and a significant increase in isovolumetric relaxation time (IRT), myocardial performance index (MPI), and LVEDP, showing impaired diastolic function, without any sex-related differences. Switching to a SD after 4 weeks of WD partially reversed the cardiac systolic and diastolic dysfunction. A diet rich in saturated fat and sugars (WD) impairs cardiac systolic and diastolic function in the mouse. Further studies are required to define the mechanism through which diet affects cardiac function, and whether dietary interventions can be used in patients with, or at risk for, HF. Published by Elsevier Ireland Ltd.

Modelling of subarachnoid space width changes in apnoea resulting as a function of blood flow parameters.

PubMed

Kalicka, Renata; Mazur, Kamila; Wolf, Jacek; Frydrychowski, Andrzej F; Narkiewicz, Krzysztof; Winklewski, Pawel J

2017-09-01

During apnoea, the pial artery is subjected to two opposite physiological processes: vasoconstriction due to elevated blood pressure and vasorelaxation driven by rising pH in the brain parenchyma. We hypothesized that the pial artery response to apnoea may vary, depending on which process dominate. Apnoea experiments were performed in a group of 19 healthy, non-smoking volunteers (9 men and 10 women). The following parameters were obtained for further analysis: blood pressure, the cardiac (from 0.5 to 5.0Hz) and slow (<0.5Hz) components of subarachnoid space width, heart rate, mean cerebral blood flow velocity in the internal carotid artery, pulsatility and resistivity index, internal carotid artery diameter, blood oxygen saturation and end-tidal carbon dioxide. The experiment consisted of three apnoeas, sequentially: 30s, 60s and maximal apnoea. The breath-hold was separated for 5minute rest. The control process is sophisticated, involving internal cross-couplings and cross-dependences. The aim of work was to find a mathematical dependence between data. Unexpectedly, the modelling revealed two different reactions, on the same experimental procedure. As a consequence, there are two subsets of cardiac subarachnoid space width responses to breath-hold in humans. A positive cardiac subarachnoid space width change to apnoea depends on changes in heart rate and cerebral blood flow velocity. A negative cardiac subarachnoid space width change to apnoea is driven by heart rate, mean arterial pressure and pulsatility index changes. The described above two different reactions to experimental breath-hold provides new insights into our understanding of the complex mechanisms governing the adaptation to apnoea in humans. We proposed a mathematical methodology that can be used in further clinical research. Copyright © 2017 Elsevier Inc. All rights reserved.

Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

PubMed

Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

2017-08-01

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed in transgenic chronic heart failure mice, evaluated in the critical period between the occurrence of an impairment of cardiac function and the terminal stage of the disease. Exercise training improved exercise performance and cardiac function, but it did not affect the impaired mitochondrial respiration. Factors "upstream" of mitochondria, including an enhanced cardiovascular O 2 delivery, were mainly responsible for the functional improvement. Copyright © 2017 the American Physiological Society.

Beneficial role of tamoxifen in experimentally induced cardiac hypertrophy.

PubMed

Patel, Bhoomika M; Desai, Vishal J

2014-04-01

Protein kinase C (PKC) activation is associated with cardiac hypertrophy (CH), fibrosis, inflammation and cardiac dysfunction. Tamoxifen is a PKC inhibitor. Despite these, reports on effect of tamoxifen on cardiac hypertrophy are not available. Hence, we have investigated effect of tamoxifen (2mg/kg/day, po) on CH. In isoproterenol (ISO) induced CH, ISO (5mg/kg/day, ip) was administered for 10 days in Wistar rats. For partial abdominal aortic constriction (PAAC), abdominal aorta was ligated by 4-0 silk thread around 7.0mm diameter blunt needle. Then the needle was removed to leave the aorta partially constricted for 30 days. Tamoxifen was given for 10 days and 30 days, respectively, in ISO and PAAC models and at end of each studies, animals were sacrificed and biochemical and cardiac parameters were evaluated. ISO and PAAC produced significant dyslipidemia, hypertension, bradycardia, oxidative stress and increase in serum lactate dehydrogenase and creatine kinase-MB, C-reactive protein. Treatment with tamoxifen significantly controlled dyslipidemia, hypertension, bradycardia, oxidative stress and reduced serum cardiac markers. ISO control and PAAC control rats exhibited significantly increased cardiac and left ventricular (LV) hypertrophic index, LV thickness, cardiomyocyte diameter. Treatment with tamoxifen significantly reduced these hypertrophic indices. There was a significant increase in LV collagen level, decrease in Na(+)K(+)ATPase activity, and reduction in the rate of pressure development and decay. Tamoxifen significantly reduced LV collagen, increased Na(+)K(+)ATPase activity and improved hemodynamic function. This was further supported by histopathological studies, in which tamoxifen showed marked decrease in fibrosis and increase in extracellular spaces in the treated animals. Our data suggest that tamoxifen produces beneficial effects on cardiac hypertrophy and hence may be considered as a preventive measure for cardiac hypertrophy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

48-hours administration of fenoterol in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

PubMed

Grzesiak, Mariusz; Hincz, Piotr; Forys, Sebastian; Ahmed, Rehana B; Wilczynski, Jan

2013-01-01

The aims were to investigate whether any changes in placental and fetal circulation were observed during fenoterol tocolysis within the first 48 hours of therapy. Doppler evaluation of placental and fetal circulation was performed prior to fenoterol administration and then after 24 and 48 hours. Maternal heart rate and pulsatility index (PI) in uterine arteries were assessed. FHR, RI and PI of umbilical artery and middle cerebral artery were measured. E/A ratio for A-V valves, the myocardial performance index (MPI) and shortening fraction (SF) were calculated for both ventricles independently. The blood flow pattern in DV was assessed using PI, S/a ratio and peak velocity index for the vein. To determine changes over time in all study variable analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. Uterine and fetal arterial blood flow patterns were not altered significantly during 48 hours of tocolysis. No significant changes were observed in fetal cardiac function parameters as well. The evaluation of Doppler parameters in the DV revealed a significant increase in PVIV after 48 hours. Additionally after 48 hours of successful tocolysis S/a ratio values were significantly lower. Short term intravenous administration of fenoterol seems not to alter uterine and fetal arterial blood flow pattern. Direct fetal cardiac function remained unaffected. However significant changes of selected Doppler parameters in DV may suggest further studies should be performed to assess more precisely fetal venous blood flow.

A computer model of the pediatric circulatory system for testing pediatric assist devices.

PubMed

Giridharan, Guruprasad A; Koenig, Steven C; Mitchell, Michael; Gartner, Mark; Pantalos, George M

2007-01-01

Lumped parameter computer models of the pediatric circulatory systems for 1- and 4-year-olds were developed to predict hemodynamic responses to mechanical circulatory support devices. Model parameters, including resistance, compliance and volume, were adjusted to match hemodynamic pressure and flow waveforms, pressure-volume loops, percent systole, and heart rate of pediatric patients (n = 6) with normal ventricles. Left ventricular failure was modeled by adjusting the time-varying compliance curve of the left heart to produce aortic pressures and cardiac outputs consistent with those observed clinically. Models of pediatric continuous flow (CF) and pulsatile flow (PF) ventricular assist devices (VAD) and intraaortic balloon pump (IABP) were developed and integrated into the heart failure pediatric circulatory system models. Computer simulations were conducted to predict acute hemodynamic responses to PF and CF VAD operating at 50%, 75% and 100% support and 2.5 and 5 ml IABP operating at 1:1 and 1:2 support modes. The computer model of the pediatric circulation matched the human pediatric hemodynamic waveform morphology to within 90% and cardiac function parameters with 95% accuracy. The computer model predicted PF VAD and IABP restore aortic pressure pulsatility and variation in end-systolic and end-diastolic volume, but diminish with increasing CF VAD support.

Cardiac mTOR rescues the detrimental effects of diet-induced obesity in the heart after ischemia-reperfusion.

PubMed

Aoyagi, Toshinori; Higa, Jason K; Aoyagi, Hiroko; Yorichika, Naaiko; Shimada, Briana K; Matsui, Takashi

2015-06-15

Diet-induced obesity deteriorates the recovery of cardiac function after ischemia-reperfusion (I/R) injury. While mechanistic target of rapamycin (mTOR) is a key mediator of energy metabolism, the effects of cardiac mTOR in ischemic injury under metabolic syndrome remains undefined. Using cardiac-specific transgenic mice overexpressing mTOR (mTOR-Tg mice), we studied the effect of mTOR on cardiac function in both ex vivo and in vivo models of I/R injury in high-fat diet (HFD)-induced obese mice. mTOR-Tg and wild-type (WT) mice were fed a HFD (60% fat by calories) for 12 wk. Glucose intolerance and insulin resistance induced by the HFD were comparable between WT HFD-fed and mTOR-Tg HFD-fed mice. Functional recovery after I/R in the ex vivo Langendorff perfusion model was significantly lower in HFD-fed mice than normal chow diet-fed mice. mTOR-Tg mice demonstrated better cardiac function recovery and had less of the necrotic markers creatine kinase and lactate dehydrogenase in both feeding conditions. Additionally, mTOR overexpression suppressed expression of proinflammatory cytokines, including IL-6 and TNF-α, in both feeding conditions after I/R injury. In vivo I/R models showed that at 1 wk after I/R, HFD-fed mice exhibited worse cardiac function and larger myocardial scarring along myofibers compared with normal chow diet-fed mice. In both feeding conditions, mTOR overexpression preserved cardiac function and prevented myocardial scarring. These findings suggest that cardiac mTOR overexpression is sufficient to prevent the detrimental effects of diet-induced obesity on the heart after I/R, by reducing cardiac dysfunction and myocardial scarring. Copyright © 2015 the American Physiological Society.

Effects of changing heart rate on electrophysiological and hemodynamic function in the dog.

PubMed

Hamlin, Robert L; Nakayama, Tomohiro; Nakayama, Hitomi; Carnes, Cynthia A

2003-03-14

Cardiovascular parameters were measured in dogs after RR interval was changed from 0.25 s to 1.2 s with atropine and graded doses of zatebradine, an I(f)-channel blocker. Left ventricular (LV) pre-ejection period (PEP), systemic vascular resistance, tau (an estimate of myocardial stiffness), PQ, QTc, dLVP/dt(max) and dLVP/dt(min), aortic pressure, and right atrial pressure did not change when each parameter was plotted against RR interval (r(2)'s < or = 0.5). LV end-diastolic pressure, stroke volume index, LV ejection time (ET), and QT all increased either linearly or curvilinearly as RR interval prolonged. Cardiac output index and PEP/ET decreased curvilinearly. When heart rate (HR) was fixed by pacing, and graded doses of zatebradine were given, changes in cardiovascular function were minimal. Thus zatebradine affects cardiovascular function principally by changing HR and not by affecting function directly. This study provides data on the effects of changing HR, alone, on cardiovascular parameters measured frequently during pharmacological and toxicological studies. It should prove useful when physiological variables, including HR, change, and there is need to know what change in HR, alone, contributes.

Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: potential role in obesity.

PubMed

Martínez-Martínez, Ernesto; Jurado-López, Raquel; Valero-Muñoz, María; Bartolomé, María Visitación; Ballesteros, Sandra; Luaces, María; Briones, Ana María; López-Andrés, Natalia; Miana, María; Cachofeiro, Victoria

2014-05-01

Leptin acts as a cardiac profibrotic factor. However, the mechanisms underlying this effect are unclear. Therefore, we sought to elucidate the mediators involved in this process and the potential role of leptin in cardiac fibrosis associated with obesity. Male Wistar rats were fed either a high-fat diet (HFD; 33.5% fat), or a standard diet (3.5% fat) for 6 weeks. HFD animals show cardiac hypertrophy, fibrosis and an increase in O2- production as evaluated by dihydroethidium. Echocardiographic parameters of cardiac structure and systolic function were similar in both groups. Cardiac levels of leptin, collagen I, galectin-3 and transforming growth factor β (TGF-β) were higher in HFD than in controls. In cardiac myofibroblasts, leptin (10-100 ng/ml) increased O2-, collagen I, galectin-3, TGF-β and connective tissue growth factor production (CTGF). These effects were prevented by the presence of either melatonin (10 mmol/l) or the inhibitor of mTOR, rapamycin (10 mmol/l). Blockage of galectin-3 activity by N-acetyllactosamine (LacNac 10 mmol/l) reduced both collagen I and O2(*-) production induced by leptin. The p70S6 kinase activation/phosphorylation, the downstream mediator of mTOR, induced by leptin was not modified by melatonin. Leptin reduced the metalloproteinase (MMP) 2 activity and the presence of melatonin, rapamycin or LacNac were unable to prevent it. The data suggest that leptin locally produced in the heart could participate in the fibrosis observed in HFD by affecting collagen turnover. Collagen synthesis induced by leptin seems to be mediated by the production of galectin-3, TGF-β and CTGF through oxidative stress increased by activation of mTOR pathway.

Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension.

PubMed

van Brussel, Peter M; Eeftinck Schattenkerk, Daan W; Dobrowolski, Linn C; de Winter, Robbert J; Reekers, Jim A; Verberne, Hein J; Vogt, Liffert; van den Born, Bert-Jan H

2016-01-01

Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity and cardiovascular parameters. A total of 21 consecutive patients with refractory hypertension (daytime ambulatory blood pressure (BP)≥150/100 mmHg despite the use of 3 or more antihypertensive drugs), no evidence for secondary hypertension and normal renovascular anatomy were included. RSD was performed with the Medtronic Symplicity renal denervation catheter with an average of 4.2 (range 3-6) ablations per renal artery. To assess cardiac sympathetic activity, 123I-mIBG cardiac scintigraphy was performed before and 6 weeks after. In addition, the effect of RSD on peripheral BP and cardiac hemodynamics were assessed non-invasively. 123I-mIBG uptake before and after RSD was 1.7±0.4% vs. 1.7±0.5% at 15 min. and 1.4±0.4% vs. 1.5±0.5% after 4 h. As a consequence, washout rate was similar before (33.7±11.7%) and after RSD (30.1±12.6%, p=0.27). In line with earlier RSD studies, a significant drop in systolic office BP (-12.2 mmHg, p=0.04) was detected, whereas the decrease in ambulatory BP was not significant. No changes were seen in heart rate, stroke volume or left ventricular contractility, both in supine position and after standing. In concert with previous reports, RSD leads to a significant drop in office BP. However, a reduction in sympathetic activity could not be demonstrated on a cardiac level. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of Obesity on Cardiovascular Hemodynamics, Cardiac Morphology, and Ventricular Function.

PubMed

Alpert, Martin A; Omran, Jad; Bostick, Brian P

2016-12-01

Obesity produces a variety of hemodynamic alterations that may cause changes in cardiac morphology which predispose to left and right ventricular dysfunction. Various neurohormonal and metabolic alterations commonly associated with obesity may contribute to these abnormalities of cardiac structure and function. These changes in cardiovascular hemodynamics, cardiac morphology, and ventricular function may, in severely obese patients, predispose to heart failure, even in the absence of other forms of heart disease (obesity cardiomyopathy). In normotensive obese patients, cardiac involvement is commonly characterized by elevated cardiac output, low peripheral vascular resistance, and increased left ventricular (LV) end-diastolic pressure. Sleep-disordered breathing may lead to pulmonary arterial hypertension and, in association with left heart failure, may contribute to elevation of right heart pressures. These alterations, in association with various neurohormonal and metabolic abnormalities, may produce LV hypertrophy; impaired LV diastolic function; and less commonly, LV systolic dysfunction. Many of these alterations are reversible with substantial voluntary weight loss.

Self-Efficacy as a Marker of Cardiac Function and Predictor of Heart Failure Hospitalization and Mortality in Patients With Stable Coronary Heart Disease: Findings From the Heart and Soul Study

PubMed Central

Sarkar, Urmimala; Ali, Sadia; Whooley, Mary A.

2009-01-01

Objective The authors sought to evaluate the association of self-efficacy with objective measures of cardiac function, subsequent hospitalization for heart failure (HF), and all-cause mortality. Design Observational cohort of ambulatory patients with stable CHD. The authors measured self-efficacy using a published, validated, 5-item summative scale, the Sullivan Self-Efficacy to Maintain Function Scale. The authors also performed a cardiac assessment, including an exercise treadmill test with stress echocardiography. Main Outcome Measures Hospitalizations for HF, as determined by blinded review of medical records, and all-cause mortality, with adjustment for demographics, medical history, medication use, depressive symptoms, and social support. Results Of the 1,024 predominately male, older CHD patients, 1013 (99%) were available for follow-up, 124 (12%) were hospitalized for HF, and 235 (23%) died during 4.3 years of follow-up. Mean cardiac self-efficacy score was 9.7 (SD 4.5, range 0–20), corresponding to responses between “not at all confident” and “somewhat confident” for ability to maintain function. Lower self-efficacy predicted subsequent HF hospitalization (OR per SD decrease = 1.4, p = 0006), and all-cause mortality (OR per SD decrease = 1.4, p < .0001). After adjustment, the association of cardiac self-efficacy with both HF hospitalization and mortality was explained by worse baseline cardiac function. Conclusion Among patients with CHD, self-efficacy was a reasonable proxy for predicting HF hospitalizations. The increased risk of HF associated with lower baseline self-efficacy was explained by worse cardiac function. These findings indicate that measuring cardiac self-efficacy provides a rapid and potentially useful assessment of cardiac function among outpatients with CHD. PMID:19290708

Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

PubMed

Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

2014-11-01

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

PubMed

Meana, Clara; Rubín, José Manuel; Bordallo, Carmen; Suárez, Lorena; Bordallo, Javier; Sánchez, Manuel

2016-02-01

Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of polyamines in different stages of heart failure. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Use of radiotelemetry to assess perinatal cardiac function in the ovine fetus and newborn.

PubMed

Antolic, A; Wood, C E; Keller-Wood, M

2017-12-01

The late gestation fetal ECG (fECG) has traditionally been difficult to characterize due to the low fECG signal relative to high maternal noise. Although new technologies have improved the feasibility of its acquisition and separation, little is known about its development in late gestation, a period in which the fetal heart undergoes extensive maturational changes. Here, we describe a method for the chronic implantation of radiotelemetry devices into late gestation ovine fetuses to characterize parameters of the fECG following surgery, throughout late gestation, and in the perinatal period. We found no significant changes in mean aortic pressure (MAP), heart rate (HR), or ECG in the 5 days following implantation; however, HR decreased in the first 24 h following the end of surgery, with associated increases in RR, PR, and QRS intervals. Over the last 14 days of fetal life, fetal MAP significantly increased, and HR significantly decreased, as expected. MAP and HR increased as labor progressed. Although there were no significant changes over time in the ECG during late gestation, the duration of the PR interval initially decreased and then increased as birth approached. These results indicate that although critical maturational changes occur in the late gestation fetal myocardium, the mechanisms that control the cardiac conduction are relatively mature in late gestation. The study demonstrates that radiotelemetry can be successfully used to assess fetal cardiac function, in particular conduction, through the process of labor and delivery, and may therefore be a useful tool for study of peripartum cardiac events. Copyright © 2017 the American Physiological Society.

Exercise Physiology and Pulmonary Hemodynamic Abnormality in PH Patients with Exercise Induced Venous-To-Systemic Shunt.

PubMed

Guo, Jian; Shi, Xue; Yang, Wenlan; Gong, Sugang; Zhao, Qinhua; Wang, Lan; He, Jing; Shi, Xiaofang; Sun, Xingguo; Liu, Jinming

2014-01-01

To identify the pulmonary hypertension (PH) patients who develop an exercise induced venous-to-systemic shunt (EIS) by performing the cardiopulmonary exercise test (CPET), analyse the changes of CPET measurements during exercise and compare the exercise physiology and resting pulmonary hemodynamics between shunt-PH and no-shunt-PH patients. Retrospectively, resting pulmonary function test (PFT), right heart catheterization (RHC), and CPET for clinical evaluation of 104 PH patients were studied. Considering all 104 PH patients by three investigators, 37 were early EIS+, 61 were EIS-, 3 were late EIS+, and 3 others were placed in the discordant group. PeakVO2, AT and OUES were all reduced in the shunt-PH patients compared with the no-shunt-PH subjects, whereas VE/VCO2 slope and the lowest VE/VCO2 increased. Besides, the changes and the response characteristics of the key CPET parameters at the beginning of exercise in the shunt group were notably different from those of the no shunt one. At cardiac catheterization, the shunt patients had significantly increased mean pulmonary artery pressure (mPAP), mean right atrial pressure (mRAP) and pulmonary vascular resistance (PVR), reduced cardiac output (CO) and cardiac index (CI) compared with the no shunt ones (P<0.05). Resting CO was significantly correlated with exercise parameters of AT (r = 0.527, P<0.001), OUES (r = 0.410, P<0.001) and Peak VO2 (r = 0.405, P<0.001). PVR was significantly, but weakly, correlated with the above mentioned CPET parameters. CPET may allow a non-invasive method for detecting an EIS and assessing the severity of the disease in PH patients.

Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies.

PubMed

Morcos, Peter N; Bogman, Katrijn; Hubeaux, Stanislas; Sturm-Pellanda, Carolina; Ruf, Thorsten; Bordogna, Walter; Golding, Sophie; Zeaiter, Ali; Abt, Markus; Balas, Bogdana

2017-03-01

Alectinib, a central nervous system (CNS)-active ALK inhibitor, has demonstrated efficacy and safety in ALK+ non-small-cell lung cancer that has progressed following crizotinib treatment. Other ALK inhibitors have shown concentration-dependent QTc prolongation and treatment-related bradycardia. Therefore, this analysis evaluated alectinib safety in terms of electrophysiologic parameters. Intensive triplicate centrally read electrocardiogram (ECG) and matched pharmacokinetic data were collected across two alectinib single-arm trials. Analysis of QTcF included central tendency analysis [mean changes from baseline with one-sided upper 95% confidence intervals (CIs)], categorical analyses, and relationship between change in QTcF and alectinib plasma concentrations. Alectinib effects on other ECG parameters (heart rate, PR interval and QRS duration) were also evaluated. Alectinib did not cause a clinically relevant change in QTcF. The maximum mean QTcF change from baseline was 5.3 ms observed pre-dose at week 2. The upper one-sided 95% CI was <10 ms at all time points. There was no relevant relationship between change in QTcF and alectinib plasma concentrations. Alectinib treatment resulted in a generally asymptomatic exposure-dependent decrease in mean heart rate of ~11 to 13 beats per minute at week 2. No clinically relevant effects were seen on other ECG parameters. Approximately 5% of patients reported cardiac adverse events of bradycardia or sinus bradycardia; however, these were all grade 1-2. Alectinib does not prolong the QTc interval or cause changes in cardiac function to a clinically relevant extent, with the exception of a decrease in heart rate which was generally asymptomatic.

[Cardiac failure in endocrine diseases].

PubMed

Hashizume, K

1993-05-01

Several endocrine diseases show the symptoms of cardiac failure. Among them, patients with acromegaly show a specific cardiomyopathy which results in a severe left-sided cardiac failure. Hypoparathyroidism also induces cardiac failure, which is resulted from hypocalcemia and low levels of serum parathyroid hormone. In the cases of hypothyroidism, the patients with myxedemal coma show a severe cardiac failure, which is characterized by disturbance of central nervous system, renal function, and cardiac function. In the patients with thyroid crisis (storm), the cardiac failure comes from the great reduction of cardiac output with dehydration. The reduction of circulation volume, observed in the patients with pheochromocytoma easily induces cardiac failure (shock) just after the removal of adrenal tumor. In patients with malignant carcinoid syndrome, right-sided ventricular failure which may be occurred through the actions of biogenic amines is observed.

Cardiac Fibroblast: The Renaissance Cell

PubMed Central

Souders, Colby A.; Bowers, Stephanie L.K.; Baudino, Troy A.

2012-01-01

The permanent cellular constituents of the heart include cardiac fibroblasts, myocytes, endothelial cells and vascular smooth muscle cells. Previous studies have demonstrated that there are undulating changes in cardiac cell populations during embryonic development, through neonatal development and into the adult. Transient cell populations include lymphocytes, mast cells and macrophages, which can interact with these permanent cell types to affect cardiac function. It has also been observed that there are marked differences in the makeup of the cardiac cell populations depending on the species, which may be important when examining myocardial remodeling. Current dogma states that the fibroblast makes up the largest cell population of the heart; however, this appears to vary for different species, especially mice. Cardiac fibroblasts play a critical role in maintaining normal cardiac function, as well as in cardiac remodeling during pathological conditions such as myocardial infarct and hypertension. These cells have numerous functions, including synthesis and deposition of extracellular matrix, cell-cell communication with myocytes, cell-cell signaling with other fibroblasts, as well as with endothelial cells. These contacts affect the electrophysiological properties, secretion of growth factors and cytokines, as well as potentiating blood vessel formation. While a plethora of information is known about several of these processes, relatively little is understood about fibroblasts and their role in angiogenesis during development or cardiac remodeling. In this review we provide insight into the various properties of cardiac fibroblasts that helps illustrate their importance in maintaining proper cardiac function, as well as their critical role in the remodeling heart. PMID:19959782

Interoception across Modalities: On the Relationship between Cardiac Awareness and the Sensitivity for Gastric Functions

PubMed Central

Herbert, Beate M.; Muth, Eric R.; Pollatos, Olga; Herbert, Cornelia

2012-01-01

The individual sensitivity for ones internal bodily signals (“interoceptive awareness”) has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals (“cardiac awareness”) which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG) and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality. PMID:22606278

An automatic alignment tool to improve repeatability of left ventricular function and dyssynchrony parameters in serial gated myocardial perfusion SPECT studies

PubMed Central

Zhou, Yanli; Faber, Tracy L.; Patel, Zenic; Folks, Russell D.; Cheung, Alice A.; Garcia, Ernest V.; Soman, Prem; Li, Dianfu; Cao, Kejiang; Chen, Ji

2013-01-01

Objective Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI. Methods Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters. Results The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing. Conclusion The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI. PMID:23211996

Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms

PubMed Central

Iorga, Bogdan; Schwanke, Kristin; Weber, Natalie; Wendland, Meike; Greten, Stephan; Piep, Birgit; dos Remedios, Cristobal G.; Martin, Ulrich; Zweigerdt, Robert; Kraft, Theresia; Brenner, Bernhard

2018-01-01

Characterizing the contractile function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is key for advancing their utility for cellular disease models, promoting cell based heart repair, or developing novel pharmacological interventions targeting cardiac diseases. The aim of the present study was to understand whether steady-state and kinetic force parameters of β-myosin heavy chain (βMyHC) isoform-expressing myofibrils within human embryonic stem cell-derived cardiomyocytes (hESC-CMs) differentiated in vitro resemble those of human ventricular myofibrils (hvMFs) isolated from adult donor hearts. Contractile parameters were determined using the same micromechanical method and experimental conditions for both types of myofibrils. We identified isoforms and phosphorylation of main sarcomeric proteins involved in the modulation of force generation of both, chemically demembranated hESC-CMs (d-hESC-CMs) and hvMFs. Our results indicate that at saturating Ca2+ concentration, both human-derived contractile systems developed forces with similar rate constants (0.66 and 0.68 s−1), reaching maximum isometric force that was significantly smaller for d-hESC-CMs (42 kPa) than for hvMFs (94 kPa). At submaximal Ca2+-activation, where intact cardiomyocytes normally operate, contractile parameters of d-hESC-CMs and hvMFs exhibited differences. Ca2+ sensitivity of force was higher for d-hESC-CMs (pCa50 = 6.04) than for hvMFs (pCa50 = 5.80). At half-maximum activation, the rate constant for force redevelopment was significantly faster for d-hESC-CMs (0.51 s−1) than for hvMFs (0.28 s−1). During myofibril relaxation, kinetics of the slow force decay phase were significantly faster for d-hESC-CMs (0.26 s−1) than for hvMFs (0.21 s−1), while kinetics of the fast force decay were similar and ~20x faster. Protein analysis revealed that hESC-CMs had essentially no cardiac troponin-I, and partially non-ventricular isoforms of some other sarcomeric proteins, explaining the functional discrepancies. The sarcomeric protein isoform pattern of hESC-CMs had features of human cardiomyocytes at an early developmental stage. The study indicates that morphological and ultrastructural maturation of βMyHC isoform-expressing hESC-CMs is not necessarily accompanied by ventricular-like expression of all sarcomeric proteins. Our data suggest that hPSC-CMs could provide useful tools for investigating inherited cardiac diseases affecting contractile function during early developmental stages. PMID:29403388

Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies.

PubMed

Kanaan, Georges N; Ichim, Bianca; Gharibeh, Lara; Maharsy, Wael; Patten, David A; Xuan, Jian Ying; Reunov, Arkadiy; Marshall, Philip; Veinot, John; Menzies, Keir; Nemer, Mona; Harper, Mary-Ellen

2018-04-01

Glutaredoxin 2 (GRX2), a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC) to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.

PubMed

Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng

2016-05-01

Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.

AMP-Activated Protein Kinase Deficiency Rescues Paraquat-Induced Cardiac Contractile Dysfunction Through an Autophagy-Dependent Mechanism

PubMed Central

Wang, Qiurong; Yang, Lifang; Hua, Yinan; Nair, Sreejayan; Xu, Xihui; Ren, Jun

2014-01-01

Aim: Paraquat, a quaternary nitrogen herbicide, is a highly toxic prooxidant resulting in multi-organ failure including the heart although the underlying mechanism still remains elusive. This study was designed to examine the role of the cellular fuel sensor AMP-activated protein kinase (AMPK) in paraquat-induced cardiac contractile and mitochondrial injury. Results: Wild-type and transgenic mice with overexpression of a mutant AMPK α2 subunit (kinase dead, KD), with reduced activity in both α1 and α2 subunits, were administered with paraquat (45 mg/kg) for 48 h. Paraquat elicited cardiac mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic diameter and reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca2+ handling, reduced cell survival, and overt mitochondrial damage (loss in mitochondrial membrane potential). In addition, paraquat treatment promoted phosphorylation of AMPK and autophagy. Interestingly, deficiency in AMPK attenuated paraquat-induced cardiac contractile and intracellular Ca2+ derangement. The beneficial effect of AMPK inhibition was associated with inhibition of the AMPK-TSC-mTOR-ULK1 signaling cascade. In vitro study revealed that inhibitors for AMPK and autophagy attenuated paraquat-induced cardiomyocyte contractile dysfunction. Conclusion: Taken together, our findings revealed that AMPK may mediate paraquat-induced myocardial anomalies possibly by regulating the AMPK/mTOR-dependent autophagy. PMID:25092649

The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults.

PubMed

Shah, A S; Khoury, P R; Dolan, L M; Ippisch, H M; Urbina, E M; Daniels, S R; Kimball, T R

2011-04-01

We sought to evaluate the effects of obesity and obesity-related type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and diastolic function in adolescents and young adults. Cardiac structure and function were compared by echocardiography in participants who were lean, obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study. Group differences were assessed using ANOVA. Independent determinants of cardiac outcome measures were evaluated with general linear models. Adolescents with obesity and obesity-related type 2 diabetes were found to have abnormal cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05). These two groups also had increased systolic function. Diastolic function decreased from the lean to obese to obese diabetic groups with the lowest diastolic function observed in the obese diabetic group (p < 0.05). Regression analysis showed that group, BMI z score (BMIz), group × BMIz interaction and systolic BP z score (BPz) were significant determinants of cardiac structure, while group, BMIz, systolic BPz, age and fasting glucose were significant determinants of the diastolic function (all p < 0.05). Adolescents with obesity and obesity-related type 2 diabetes demonstrate changes in cardiac geometry consistent with cardiac remodelling. These two groups also demonstrate decreased diastolic function compared with lean controls, with the greatest decrease observed in those with type 2 diabetes. Adults with diastolic dysfunction are known to be at increased risk of progressing to heart failure. Therefore, our findings suggest that adolescents with obesity-related type 2 diabetes may be at increased risk of progressing to early heart failure compared with their obese and lean counterparts.

Transgenic Analysis of the Role of FKBP12.6 in Cardiac Function and Intracellular Calcium Release

PubMed Central

Liu, Ying; Chen, Hanying; Ji, Guangju; Li, Baiyan; Mohler, Peter J.; Zhu, Zhiming; Yong, Weidong; Chen, Zhuang; Xu, Xuehong

2011-01-01

Abstract FK506 binding protein12.6 (FKBP12.6) binds to the Ca2+ release channel ryanodine receptor (RyR2) in cardiomyocytes and stabilizes RyR2 to prevent premature sarcoplasmic reticulum Ca2+ release. Previously, two different mouse strains deficient in FKBP12.6 were reported to have different abnormal cardiac phenotypes. The first mutant strain displayed sex-dependent cardiac hypertrophy, while the second displayed exercise-induced cardiac arrhythmia and sudden death. In this study, we tested whether FKBP12.6-deficient mice that display hypertrophic hearts can develop exercise-induced cardiac sudden death and whether the hypertrophic heart is a direct consequence of abnormal calcium handling in mutant cardiomyocytes. Our data show that FKBP12.6-deficient mice with cardiac hypertrophy do not display exercise-induced arrhythmia and/or sudden cardiac death. To investigate the role of FKBP12.6 overexpression for cardiac function and cardiomyocyte calcium release, we generated a transgenic mouse line with cardiac specific overexpression of FKBP12.6 using α-myosin heavy chain (αMHC) promoter. MHC-FKBP12.6 mice displayed normal cardiac development and function. We demonstrated that MHC-FKBP12.6 mice are able to rescue abnormal cardiac hypertrophy and abnormal calcium release in FKBP12.6-deficient mice. PMID:22087651

Quantification of left ventricular functional parameter values using 3D spiral bSSFP and through-time non-Cartesian GRAPPA.

PubMed

Barkauskas, Kestutis J; Rajiah, Prabhakar; Ashwath, Ravi; Hamilton, Jesse I; Chen, Yong; Ma, Dan; Wright, Katherine L; Gulani, Vikas; Griswold, Mark A; Seiberlich, Nicole

2014-09-11

The standard clinical acquisition for left ventricular functional parameter analysis with cardiovascular magnetic resonance (CMR) uses a multi-breathhold multi-slice segmented balanced SSFP sequence. Performing multiple long breathholds in quick succession for ventricular coverage in the short-axis orientation can lead to fatigue and is challenging in patients with severe cardiac or respiratory disorders. This study combines the encoding efficiency of a six-fold undersampled 3D stack of spirals balanced SSFP sequence with 3D through-time spiral GRAPPA parallel imaging reconstruction. This 3D spiral method requires only one breathhold to collect the dynamic data. Ten healthy volunteers were recruited for imaging at 3 T. The 3D spiral technique was compared against 2D imaging in terms of systolic left ventricular functional parameter values (Bland-Altman plots), total scan time (Welch's t-test) and qualitative image rating scores (Wilcoxon signed-rank test). Systolic left ventricular functional values were not significantly different (i.e. 3D-2D) between the methods. The 95% confidence interval for ejection fraction was -0.1 ± 1.6% (mean ± 1.96*SD). The total scan time for the 3D spiral technique was 48 s, which included one breathhold with an average duration of 14 s for the dynamic scan, plus 34 s to collect the calibration data under free-breathing conditions. The 2D method required an average of 5 min 40s for the same coverage of the left ventricle. The difference between 3D and 2D image rating scores was significantly different from zero (Wilcoxon signed-rank test, p < 0.05); however, the scores were at least 3 (i.e. average) or higher for 3D spiral imaging. The 3D through-time spiral GRAPPA method demonstrated equivalent systolic left ventricular functional parameter values, required significantly less total scan time and yielded acceptable image quality with respect to the 2D segmented multi-breathhold standard in this study. Moreover, the 3D spiral technique used just one breathhold for dynamic imaging, which is anticipated to reduce patient fatigue as part of the complete cardiac examination in future studies that include patients.

Probabilistic-driven oriented Speckle reducing anisotropic diffusion with application to cardiac ultrasonic images.

PubMed

Vegas-Sanchez-Ferrero, G; Aja-Fernandez, S; Martin-Fernandez, M; Frangi, A F; Palencia, C

2010-01-01

A novel anisotropic diffusion filter is proposed in this work with application to cardiac ultrasonic images. It includes probabilistic models which describe the probability density function (PDF) of tissues and adapts the diffusion tensor to the image iteratively. For this purpose, a preliminary study is performed in order to select the probability models that best fit the stastitical behavior of each tissue class in cardiac ultrasonic images. Then, the parameters of the diffusion tensor are defined taking into account the statistical properties of the image at each voxel. When the structure tensor of the probability of belonging to each tissue is included in the diffusion tensor definition, a better boundaries estimates can be obtained instead of calculating directly the boundaries from the image. This is the main contribution of this work. Additionally, the proposed method follows the statistical properties of the image in each iteration. This is considered as a second contribution since state-of-the-art methods suppose that noise or statistical properties of the image do not change during the filter process.

The cardioprotective effect of thymoquinone on ischemia-reperfusion injury in isolated rat heart via regulation of apoptosis and autophagy.

PubMed

Xiao, Junhui; Ke, Zun-Ping; Shi, Yan; Zeng, Qiutang; Cao, Zhe

2018-06-22

Thymoquinone (TQ), as the active constituents of black cumin (Nigella sativa) seed oil, has been reported to have potential protective effects on the cardiovascular system. This study aimed to investigate the effects and the underlying mechanisms of TQ on myocardial ischemia-reperfusion (I/R) injury in Langendorff-perfused rat hearts. Wister rat hearts were subjected to I/R and the experimental group were pretreated with TQ prior to I/R. Hemodynamic parameters, myocardial infarct size, cardiac marker enzymes, superoxide dismutase (SOD), malondialdehyde (MDA) content, and cardiomyocyte apoptosis were assayed. Compared with the untreated group, TQ preconditioning significantly improved cardiac function, reduced infarct size, decreased cardiac lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) levels, suppressed enedoxidative stress, and apoptosis. In addition, TQ treatment promoted autophagy, which was partially reversed by chloroquine (CQ), a kind of autophagy blocker. Our study suggests that TQ can protect heart against I/R injury, which is associated with anti-oxidative and anti-apoptotic effects through activation of autophagy. © 2018 Wiley Periodicals, Inc.

Automatic segmentation of 4D cardiac MR images for extraction of ventricular chambers using a spatio-temporal approach

NASA Astrophysics Data System (ADS)

Atehortúa, Angélica; Zuluaga, Maria A.; Ourselin, Sébastien; Giraldo, Diana; Romero, Eduardo

2016-03-01

An accurate ventricular function quantification is important to support evaluation, diagnosis and prognosis of several cardiac pathologies. However, expert heart delineation, specifically for the right ventricle, is a time consuming task with high inter-and-intra observer variability. A fully automatic 3D+time heart segmentation framework is herein proposed for short-axis-cardiac MRI sequences. This approach estimates the heart using exclusively information from the sequence itself without tuning any parameters. The proposed framework uses a coarse-to-fine approach, which starts by localizing the heart via spatio-temporal analysis, followed by a segmentation of the basal heart that is then propagated to the apex by using a non-rigid-registration strategy. The obtained volume is then refined by estimating the ventricular muscle by locally searching a prior endocardium- pericardium intensity pattern. The proposed framework was applied to 48 patients datasets supplied by the organizers of the MICCAI 2012 Right Ventricle segmentation challenge. Results show the robustness, efficiency and competitiveness of the proposed method both in terms of accuracy and computational load.

An infrared optical pacing system for high-throughput screening of cardiac electrophysiology in human cardiomyocytes (Conference Presentation)

NASA Astrophysics Data System (ADS)

McPheeters, Matt T.; Wang, Yves T.; Laurita, Kenneth R.; Jenkins, Michael W.

2017-02-01

Cardiomyocytes derived from human induced pluripotent stem cells (hiPS-HCM) have the potential to provide individualized therapies for patients and to test drug candidates for cardiac toxicity. In order for hiPS-CM to be useful for such applications, there is a need for high-throughput technology to rapidly assess cardiac electrophysiology parameters. Here, we designed and tested a fully contactless optical mapping (OM) and optical pacing (OP) system capable of imaging and point stimulation of hiPS-CM in small wells. OM allowed us to characterize cardiac electrophysiological parameters (conduction velocity, action potential duration, etc.) using voltage-sensitive dyes with high temporal and spatial resolution over the entire well. To improve OM signal-to-noise ratio, we tested a new voltage-sensitive dye (Fluovolt) for accuracy and phototoxicity. Stimulation is essential because most electrophysiological parameters are rate dependent; however, traditional methods utilizing electrical stimulation is difficult in small wells. To overcome this limitation, we utilized OP (λ = 1464 nm) to precisely control heart rate with spatial precision without the addition of exogenous agents. We optimized OP parameters (e.g., well size, pulse width, spot size) to achieve robust pacing and minimize the threshold radiant exposure. Finally, we tested system sensitivity using Flecainide, a drug with well described action on multiple electrophysiological properties.

Simultaneous measurement of cerebral and muscle tissue parameters during cardiac arrest and cardiopulmonary resuscitation

NASA Astrophysics Data System (ADS)

Nosrati, Reyhaneh; Ramadeen, Andrew; Hu, Xudong; Woldemichael, Ermias; Kim, Siwook; Dorian, Paul; Toronov, Vladislav

2015-03-01

In this series of animal experiments on resuscitation after cardiac arrest we had a unique opportunity to measure hyperspectral near-infrared spectroscopy (hNIRS) parameters directly on the brain dura, or on the brain through the intact pig skull, and simultaneously the muscle hNIRS parameters. Simultaneously the arterial blood pressure and carotid and femoral blood flow were recorded in real time using invasive sensors. We used a novel hyperspectral signalprocessing algorithm to extract time-dependent concentrations of water, hemoglobin, and redox state of cytochrome c oxidase during cardiac arrest and resuscitation. In addition in order to assess the validity of the non-invasive brain measurements the obtained results from the open brain was compared to the results acquired through the skull. The comparison of hNIRS data acquired on brain surface and through the adult pig skull shows that in both cases the hemoglobin and the redox state cytochrome c oxidase changed in similar ways in similar situations and in agreement with blood pressure and flow changes. The comparison of simultaneously measured brain and muscle changes showed expected differences. Overall the results show feasibility of transcranial hNIRS measurements cerebral parameters including the redox state of cytochrome oxidase in human cardiac arrest patients.

Effects of testosterone and nandrolone on cardiac function: a randomized, placebo-controlled study.

PubMed

Chung, T; Kelleher, S; Liu, P Y; Conway, A J; Kritharides, L; Handelsman, D J

2007-02-01

Androgens have striking effects on skeletal muscle, but the effects on human cardiac muscle function are not well defined, neither has the role of metabolic activation (aromatization, 5alpha reduction) of testosterone on cardiac muscle been directly studied. To assess the effects of testosterone and nandrolone, a non-amplifiable and non-aromatizable pure androgen, on cardiac muscle function in healthy young men. Double-blind, randomized, placebo-controlled, three-arm parallel group clinical trial. Ambulatory care research centre. Healthy young men randomized into three groups of 10 men. Weekly intramuscular injections of testosterone (200 mg mixed esters), nandrolone (200 mg nandrolone decanoate) or matching (2 ml arachis oil vehicle) placebo for 4 weeks. Comprehensive measures of cardiac muscle function involving transthoracic cardiac echocardiography measuring myocardial tissue velocity, peak systolic strain and strain rates, and bioimpedance measurement of cardiac output and systematic vascular resistance. Left ventricular (LV) function (LV ejection fraction, LV modified TEI index), right ventricular (RV) function (ejection area, tricuspid annular systolic planar motion, RV modified TEI index) as well as cardiac afterload (mean arterial pressure, systemic vascular resistance) and overall cardiac contractility (stroke volume, cardiac output) were within age- and gender-specific reference ranges and were not significantly (P < 0.05) altered by either androgen or placebo over 4 weeks of treatment. Minor changes remaining within normal range were observed solely within the testosterone group for: increased LV end-systolic diameter (30 +/- 7 vs. 33 +/- 5 mm, P = 0.04) and RV end-systolic area (12.8 +/- 1.3 vs. 14.6 +/- 3.3 cm(2), P = 0.04), reduced LV diastolic septal velocity (Em, 9.5 +/- 2.6 vs. 8.7 +/- 2.0 cm/s, P = 0.006), increased LV filling pressure (E/Em ratio, 7.1 +/- 1.6 vs. 8.3 +/- 1.8, P = 0.02) and shortened PR interval on the electrocardiogram (167 +/- 13 vs. 154 +/- 12, P = 0.03). Four weeks of treatment with testosterone or nandrolone had no beneficial or adverse effects compared with placebo on cardiac function in healthy young men.

Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation

PubMed Central

Bartels, Emil D.; Nielsen, Jan M.; Hellgren, Lars I.; Ploug, Thorkil; Nielsen, Lars B.

2009-01-01

Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease. PMID:19390571

Pharmacologic counter measures minimizing post-space flight orthostatic intolerance. [bed rest, drug disposition, and physiological function

NASA Technical Reports Server (NTRS)

Harrison, D. C.; Kates, R.

1982-01-01

The effect of bed rest on drug disposition and physiological function was investigated as part of a project to determine the cardiovascular effects of space flight. One group of subjects was given doses of lidocane, penicillin-G, and ICG during a control period and following seven days of bed rest. Cardiac function was evaluated by echo-cardiography. Renal function was evaluated in a second group before and after several days of bed rest. Inulin, para-aminohippurate, and dextran clearances were studied. In the first group, the post-bed rest parameters were not statistically different from the pre-bed rest valves. In the second study, renal function did not change significantly after seven days of bed rest. Plans for future research are reviewed.

Cardiac risk index as a simple geometric indicator to select patients for the heart-sparing radiotherapy of left-sided breast cancer.

PubMed

Sung, KiHoon; Choi, Young Eun; Lee, Kyu Chan

2017-06-01

This is a dosimetric study to identify a simple geometric indicator to discriminate patients who meet the selection criterion for heart-sparing radiotherapy (RT). The authors proposed a cardiac risk index (CRI), directly measurable from the CT images at the time of scanning. Treatment plans were regenerated using the CT data of 312 consecutive patients with left-sided breast cancer. Dosimetric analysis was performed to estimate the risk of cardiac mortality using cardiac dosimetric parameters, such as the relative heart volumes receiving ≥25 Gy (heart V 25 ). For each CT data set, in-field heart depth (HD) and in-field heart width (HW) were measured to generate the geometric parameters, including maximum HW (HW max ) and maximum HD (HD max ). Seven geometric parameters were evaluated as candidates for CRI. Receiver operating characteristic (ROC) curve analyses were used to examine the overall discriminatory power of the geometric parameters to select high-risk patients (heart V 25  ≥ 10%). Seventy-one high-risk (22.8%) and 241 low-risk patients (77.2%) were identified by dosimetric analysis. The geometric and dosimetric parameters were significantly higher in the high-risk group. Heart V 25 showed the strong positive correlations with all geometric parameters examined (r > 0.8, p < 0.001). The product of HD max and HW max (CRI) revealed the largest area under the curve (AUC) value (0.969) and maintained 100% sensitivity and 88% specificity at the optimal cut-off value of 14.58 cm 2 . Cardiac risk index proposed as a simple geometric indicator to select high-risk patients provides useful guidance for clinicians considering optimal implementation of heart-sparing RT. © 2016 The Royal Australian and New Zealand College of Radiologists.

Evolution of cardiorespiratory interactions with age

PubMed Central

Iatsenko, D.; Bernjak, A.; Stankovski, T.; Shiogai, Y.; Owen-Lynch, P. J.; Clarkson, P. B. M.; McClintock, P. V. E.; Stefanovska, A.

2013-01-01

We describe an analysis of cardiac and respiratory time series recorded from 189 subjects of both genders aged 16–90. By application of the synchrosqueezed wavelet transform, we extract the respiratory and cardiac frequencies and phases with better time resolution than is possible with the marked events procedure. By treating the heart and respiration as coupled oscillators, we then apply a method based on Bayesian inference to find the underlying coupling parameters and their time dependence, deriving from them measures such as synchronization, coupling directionality and the relative contributions of different mechanisms. We report a detailed analysis of the reconstructed cardiorespiratory coupling function, its time evolution and age dependence. We show that the direct and indirect respiratory modulations of the heart rate both decrease with age, and that the cardiorespiratory coupling becomes less stable and more time-variable. PMID:23858485

Evolution of cardiorespiratory interactions with age.

PubMed

Iatsenko, D; Bernjak, A; Stankovski, T; Shiogai, Y; Owen-Lynch, P J; Clarkson, P B M; McClintock, P V E; Stefanovska, A

2013-08-28

We describe an analysis of cardiac and respiratory time series recorded from 189 subjects of both genders aged 16-90. By application of the synchrosqueezed wavelet transform, we extract the respiratory and cardiac frequencies and phases with better time resolution than is possible with the marked events procedure. By treating the heart and respiration as coupled oscillators, we then apply a method based on Bayesian inference to find the underlying coupling parameters and their time dependence, deriving from them measures such as synchronization, coupling directionality and the relative contributions of different mechanisms. We report a detailed analysis of the reconstructed cardiorespiratory coupling function, its time evolution and age dependence. We show that the direct and indirect respiratory modulations of the heart rate both decrease with age, and that the cardiorespiratory coupling becomes less stable and more time-variable.

Cardiac response to whole-body heating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frey, M.A.B.; Kenney, R.A.

1979-04-01

Systolic time interval analysis was used to assess changes in ventricular function during heat stress. Seven subjects (4 M + 3 F, 22-35 yr) participated in the experiments. The heating procedure was the following: both legs of seated subjects were immersed to the knees in stirred water maintained at 42-45 C. The subjects' upper legs and trunks were enclosed in nonpermeable plastic and covered with a sheet blanket to reduce heat loss. After 30 min of heating, the water and plastic were removed. The parameters measured were HR and R-R interval, LVET, and PEP. Results were compared by t testmore » at the 0.05 significance level. The results pointed to a two-stage cardiac response to heat-vagal withdrawal followed by a strong sympathetic outflow to the heart affecting both inotropic and chronotropic characteristics.« less

Techniques for efficient, real-time, 3D visualization of multi-modality cardiac data using consumer graphics hardware.

PubMed

Levin, David; Aladl, Usaf; Germano, Guido; Slomka, Piotr

2005-09-01

We exploit consumer graphics hardware to perform real-time processing and visualization of high-resolution, 4D cardiac data. We have implemented real-time, realistic volume rendering, interactive 4D motion segmentation of cardiac data, visualization of multi-modality cardiac data and 3D display of multiple series cardiac MRI. We show that an ATI Radeon 9700 Pro can render a 512x512x128 cardiac Computed Tomography (CT) study at 0.9 to 60 frames per second (fps) depending on rendering parameters and that 4D motion based segmentation can be performed in real-time. We conclude that real-time rendering and processing of cardiac data can be implemented on consumer graphics cards.

Reversible preoperative renal dysfunction does not add to the risk of postoperative acute kidney injury after cardiac valve surgery

PubMed Central

Xu, Jia-Rui; Zhuang, Ya-Min; Liu, Lan; Shen, Bo; Wang, Yi-Mei; Luo, Zhe; Teng, Jie; Wang, Chun-Sheng; Ding, Xiao-Qiang

2017-01-01

Objective To evaluate the impact of the renal dysfunction (RD) type and change of postoperative cardiac function on the risk of developing acute kidney injury (AKI) in patients who underwent cardiac valve surgery. Method Reversible renal dysfunction (RRD) was defined as preoperative RD in patients who had not been initially diagnosed with chronic kidney disease (CKD). Cardiac function improvement (CFI) was defined as postoperative left ventricular ejection function – preoperative left ventricular ejection function (ΔEF) >0%, and cardiac function not improved (CFNI) as ΔEF ≤0%. Results Of the 4,805 (94%) cardiac valve surgery patients, 301 (6%) were RD cases. The AKI incidence in the RRD group (n=252) was significantly lower than in the CKD group (n=49) (36.5% vs 63.3%, P=0.018). The AKI and renal replacement therapy incidences in the CFI group (n=174) were significantly lower than in the CFNI group (n=127) (33.9% vs 50.4%, P=0.004; 6.3% vs 13.4%, P=0.037). After adjustment for age, gender, and other confounding factors, CKD and CKD + CFNI were identified as independent risk factors for AKI in all patients after cardiac valve surgery. Multivariate logistic regression analysis showed that the risk factors for postoperative AKI in preoperative RD patients were age, gender (male), hypertension, diabetes, chronic heart failure, cardiopulmonary bypass time (every 1 min added), and intraoperative hypotension, while CFI after surgery could reduce the risk. Conclusion For cardiac valve surgery patients, preoperative CKD was an independent risk factor for postoperative AKI, but RRD did not add to the risk. Improved postoperative cardiac function can significantly reduce the risk of postoperative AKI. PMID:29184415

Hypothyroidism and its rapid correction alter cardiac remodeling.

PubMed

Hajje, Georges; Saliba, Youakim; Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim

2014-01-01

The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

Hypothyroidism and Its Rapid Correction Alter Cardiac Remodeling

PubMed Central

Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim

2014-01-01

The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease. PMID:25333636

Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

PubMed Central

Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

2015-01-01

Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

Small interfering RNA targeting focal adhesion kinase prevents cardiac dysfunction in endotoxemia.

PubMed

Guido, Maria C; Clemente, Carolina F; Moretti, Ana I; Barbeiro, Hermes V; Debbas, Victor; Caldini, Elia G; Franchini, Kleber G; Soriano, Francisco G

2012-01-01

Sepsis and septic shock are associated with cardiac depression. Cardiovascular instability is a major cause of death in patients with sepsis. Focal adhesion kinase (FAK) is a potential mediator of cardiomyocyte responses to oxidative and mechanical stress. Myocardial collagen deposition can affect cardiac compliance and contractility. The aim of the present study was to determine whether the silencing of FAK is protective against endotoxemia-induced alterations of cardiac structure and function. In male Wistar rats, endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Cardiac morphometry and function were studied in vivo by left ventricular catheterization and histology. Intravenous injection of small interfering RNA targeting FAK was used to silence myocardial expression of the kinase. The hearts of lipopolysaccharide-injected rats showed collagen deposition, increased matrix metalloproteinase 2 activity, and myocyte hypertrophy, as well as reduced 24-h +dP/dt and -dP/dt, together with hypotension, increased left ventricular end-diastolic pressure, and elevated levels of FAK (phosphorylated and unphosphorylated). Focal adhesion kinase silencing reduced the expression and activation of the kinase in cardiac tissue, as well as protecting against the increased collagen deposition, greater matrix metalloproteinase 2 activity, and reduced cardiac contractility that occur during endotoxemia. In conclusion, FAK is activated in endotoxemia, playing a role in cardiac remodeling and in the impairment of cardiac function. This kinase represents a potential therapeutic target for the protection of cardiac function in patients with sepsis.

Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

PubMed Central

O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

2014-01-01

Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

Effect of dietary calcium deficiency on the cardiac function of broiler chickens based on electro- and echocardiography.

PubMed

Zamani Moghaddam, Abdol Karim; Hassanpour, Hossein; Soroori, Sarang; Yadegari, Mehrdad; Tajeri, Ghodsieh

2010-06-01

To determine the effects of dietary calcium deficiency on the heart function of broiler chickens based on electro- and echocardiography, chicks were reared for 42 days and fed rations with different amounts of calcium. At 28 and 42 days of age, electrocardiographic and echocardiographic parameters were assessed. There were significant reductions of R wave amplitude (leads II and aVR) in the Ca-deficient group II at 42 day of age as compared to the control. S wave amplitudes were decreased in most leads but the decrease was significant (P < 0.05) only at 28 days (lead aVL, Ca-deficient group I) and 42 days (leads III, aVR, aVF, Ca-deficient groups I and II). T wave amplitudes were significantly (P < 0.05) decreased at 42 days (leads II, aVR and aVF) in the Ca-deficient group II compared to the control group. Variations in QT, ST and RR intervals were insignificant in the Ca-deficient groups compared with the control. There was a significant (P < 0.05) increase in left ventricular diameter at end-systole and a reduction of left ventricular fractional shortening in the Ca-deficient group II at 28 and 42 days as compared to the controls. Right ventricular fractional shortening was significantly (P < 0.05) decreased only in the Ca-deficient group II at 42 days of age. These results suggest that dose-dependent dietary calcium deficiency alters variations in electro- and echocardiographic parameters which could reflect decreased cardiac function in growing broiler chickens.

Repeatability, variability and reference values of pulsed wave Doppler echocardiographic measurements in healthy Saanen goats

PubMed Central

2012-01-01

Background Pulsed wave (PW) Doppler echocardiography has become a routine non invasive cardiac diagnostic tool in most species. However, evaluation of intracardiac blood flow requires reference values, which are poorly documented in goats. The aim of this study was to test the repeatability, the variability, and to establish the reference values of PW measurements in healthy adult Saanen goats. Using a standardised PW Doppler echocardiographic protocol, 10 healthy adult unsedated female Saanen goats were investigated three times at one day intervals by the same observer. Mitral, tricuspid, aortic and pulmonary flows were measured from a right parasternal view, and mitral and aortic flows were also measured from a left parasternal view. The difference between left and right side measurements and the intra-observer inter-day repeatability were tested and then the reference values of PW Doppler echocardiographic parameters in healthy adult female Saanen goats were established. Results As documented in other species, all caprine PW Doppler parameters demonstrated a poor inter-day repeatability and a moderate variability. Tricuspid and pulmonary flows were best evaluated on the right side whereas mitral and aortic flows were best obtained on the left side, and reference values are reported for healthy adult Saanen goats. Conclusions PW Doppler echocardiography allows the measurement of intracardiac blood flow indices in goats. The reference values establishment will help interpreting these indices of cardiac function in clinical cardiac cases and developing animal models for human cardiology research. PMID:23067875

Central fat influences cardiac autonomic function in obese and overweight girls.

PubMed

Soares-Miranda, Luisa; Alves, Alberto J; Vale, Susana; Aires, Luisa; Santos, Rute; Oliveira, José; Mota, Jorge

2011-10-01

It has been suggested that upper-body fat compared with lower-body fat is more closely associated with cardiovascular abnormalities. Our objective was to analyze the relationship between central fat (CF) and cardiac autonomic (cANS) function in obese and overweight girls. Children were classified in two groups based on CF: those above (CFa(50)) and those below the 50th percentile (CFb(50)) of the entire sample. This study included 16 female children who were diagnosed as being overweight or obese (age: 14.3 ± 2.8 years; weight: 75.0 ± 15.8 kg; height: 157.1 ± 8.9 cm; body mass index: 30.1 ± 5.4; and total body fat: 40.5 ± 5.0%; Tanner stage: 4). cANS function was assessed through heart rate variability (HRV) and CF parameters by dual-energy X-ray absorptiometry. Female children with higher CF exhibited significantly higher sympathetic and lower parasympathetic modulation than those with lower CF, independently of total body fat. The data of the present study indicate that CF is associated with less favorable indexes of HRV. In addition, our findings suggest that CF might be an important measure to assess the effect of obesity on cANS function in female children.

Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations.

PubMed

Abdurrachim, Desiree; Nabben, Miranda; Hoerr, Verena; Kuhlmann, Michael T; Bovenkamp, Philipp; Ciapaite, Jolita; Geraets, Ilvy M E; Coumans, Will; Luiken, Joost J F P; Glatz, Jan F C; Schäfers, Michael; Nicolay, Klaas; Faber, Cornelius; Hermann, Sven; Prompers, Jeanine J

2017-08-01

Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Transverse aortic constriction (TAC) was performed in non-diabetic (db/+) and diabetic (db/db) mice to induce pressure overload. Magnetic resonance imaging, 31P magnetic resonance spectroscopy (MRS), 1H MRS, and 18F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. In vivo measurements were complemented with ex vivo techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status. The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Modelling the heart with the atrioventricular plane as a piston unit.

PubMed

Maksuti, Elira; Bjällmark, Anna; Broomé, Michael

2015-01-01

Medical imaging and clinical studies have proven that the heart pumps by means of minor outer volume changes and back-and-forth longitudinal movements in the atrioventricular (AV) region. The magnitude of AV-plane displacement has also shown to be a reliable index for diagnosis of heart failure. Despite this, AV-plane displacement is usually omitted from cardiovascular modelling. We present a lumped-parameter cardiac model in which the heart is described as a displacement pump with the AV plane functioning as a piston unit (AV piston). This unit is constructed of different upper and lower areas analogous with the difference in the atrial and ventricular cross-sections. The model output reproduces normal physiology, with a left ventricular pressure in the range of 8-130 mmHg, an atrial pressure of approximatly 9 mmHg, and an arterial pressure change between 75 mmHg and 130 mmHg. In addition, the model reproduces the direction of the main systolic and diastolic movements of the AV piston with realistic velocity magnitude (∼10 cm/s). Moreover, changes in the simulated systolic ventricular-contraction force influence diastolic filling, emphasizing the coupling between cardiac systolic and diastolic functions. The agreement between the simulation and normal physiology highlights the importance of myocardial longitudinal movements and of atrioventricular interactions in cardiac pumping. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Left ventricular function by echocardiogram in children with sickle cell anaemia in Mumbai, Western India.

PubMed

Tidake, Abhay; Gangurde, Pranil; Taksande, Anup; Mahajan, Ajay; Nathani, Pratap

2015-10-01

Cardiovascular events and complications are the leading cause of mortality and morbidity in patients with sickle cell disease. Cardiac abnormalities occur frequently and at an early stage in sickle cell anaemia patients, despite being more evident in adulthood. Sickle cell anaemia patients are increasingly able to reach adulthood owing to improved healthcare, and may, therefore, suffer the consequences of chronic cardiac injury. Thus, the study of cardiac abnormalities is essential in children The aim of this study was to determine the echocardiographic changes in left ventricular function in children suffering from sickle cell disease in Mumbai, Western India. The study comprised of 48 cases of sickle cell anaemia and 30 non-anaemic controls with normal haemoglobin and electrophoresis pattern. M-mode, two-dimensional, and Doppler echocardiographic measurements of patients and controls were performed according to the criteria of the American Echocardiography Society. On Doppler study, the A wave height was increased and the E/A ratio was decreased, whereas the deceleration and isovolumetric relaxation times were prolonged, which is typically seen in slowed or impaired myocardial relaxation (p<0.001). Although chamber dilatations were present, echocardiographic parameters showed no statistically significant correlation with severity of anaemia and age among the sickle cell patients. We conclude that the increased left ventricular stiffness, compared with controls, might be due to fibrosis related to ischaemia caused by SS disease in addition to wall hypertrophy.

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

PubMed

Osman, Faizel; Franklyn, Jayne A; Daykin, Jacqueline; Chowdhary, Saqib; Holder, Roger L; Sheppard, Michael C; Gammage, Michael D

2004-08-15

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

High-Resolution Tissue Doppler Imaging of the Zebrafish Heart During Its Regeneration

PubMed Central

Su, Ta-Han; Shih, Cho-Chiang

2015-01-01

Abstract The human heart cannot regenerate after injury, whereas the adult zebrafish can fully regenerate its heart even after 20% of the ventricle is amputated. Many studies have begun to reveal the cellular and molecular mechanisms underlying this regenerative process, which have exciting implications for human cardiac diseases. However, the dynamic functions of the zebrafish heart during regeneration are not yet understood. This study established a high-resolution echocardiography for tissue Doppler imaging (TDI) of the zebrafish heart to explore the cardiac functions during different regeneration phases. Experiments were performed on AB-line adult zebrafish (n=40) in which 15% of the ventricle was surgically removed. An 80-MHz ultrasound TDI based on color M-mode imaging technology was employed. The cardiac flow velocities and patterns from both the ventricular chamber and myocardium were measured at different regeneration phases relative to the day of amputation. The peak velocities of early diastolic inflow, early diastolic myocardial motion, late diastolic myocardial motion, early diastolic deceleration slope, and heart rate were increased at 3 days after the myocardium amputation, but these parameters gradually returned to close to their baseline values for the normal heart at 7 days after amputation. The peak velocities of late diastolic inflow, ventricular systolic outflow, and systolic myocardial motion did not significantly differ during the heart regeneration. PMID:25517185

Assessment of Fetal Myocardial Performance Index in Women with Placenta Previa

PubMed Central

Zhang, Na; Sun, Lijuan; Zhang, Lina; Li, Zhen; Han, Jijing; Wu, Qingqing

2017-01-01

Background This study investigated whether fetuses of placenta previa pregnancies have cardiac dysfunction by use of a modified myocardial performance index (Mod-MPI). Material/Methods A prospective cross-sectional study was conducted including 178 fetuses at 28–40 weeks of gestation. Eighty-nine fetuses of mothers with placenta previa and without pregnancy complications were recruited (placenta previa group) and matched with 89 fetuses of mothers with normal pregnancies (control group). Fetal cardiac function parameters and perinatal outcomes as well as the Mod-MPI were compared between the 2 groups. Results The median Mod-MPI was significantly increased in fetuses of mothers with placenta previa compared with controls (0.47±0.05 vs. 0.45±0.05; P<0.01). Among fetuses of mothers with or without placenta previa, the Mod-MPI was significantly higher in the incomplete placenta previa group compared with the complete placenta previa group and control group (P<0.01). An increased Mod-MPI in placenta previa pregnancies was independently associated with fetal cord pH <7.2 (odds ratio, 4.8; 95% confidence interval, 0.98–23.54; P=0.003). Conclusions There is impairment of fetal cardiac function in pregnancies with placenta previa. An increased MPI was independently associated with adverse perinatal outcomes to some extent in the placenta previa pregnancies. PMID:29242496

Hemodynamic effect and safety of intermittent sequential pneumatic compression leg sleeves in patients with congestive heart failure.

PubMed

Bickel, Amitai; Shturman, Alexander; Sergeiev, Michael; Ivry, Shimon; Eitan, Arieh; Atar, Shaul

2014-10-01

Pneumatic leg sleeves are widely used after prolonged operations for prevention of venous stasis. In healthy volunteers they increase cardiac function. We evaluated the hemodynamic effects and safety of intermittent sequential pneumatic compression (ISPC) leg sleeves in patients with chronic congestive heart failure (CHF). We studied 19 patients with systolic left ventricular dysfunction and CHF. ISPC leg sleeves, each with 10 air cells, were operated by a computerized compressor, exerting 2 cycles/min. Hemodynamic and echocardiographic parameters were measured before, during, and after ISPC activation. The baseline mean left ventricular ejection fraction was 29 ± 9.2%, median 32%, range 10%-40%. Cardiac output (from 4.26 to 4.83 L/min; P = .008) and stroke volume (from 56.1 to 63.5 mL; P = .029) increased significantly after ISPC activation, without a reciprocal increase in heart rate, and declined after sleeve deactivation. Systemic vascular resistance (SVR) decreased significantly (from 1,520 to 1,216 dyne-s/cm5; P = .0005), and remained lower than the baseline level throughout the study. There was no detrimental effect on diastolic function and no adverse clinical events, despite increased pulmonary venous return. ISPC leg sleeves in patients with chronic CHF do not exacerbate symptoms and transiently improve cardiac output through an increase in stroke volume and a reduction in SVR. Copyright © 2014 Elsevier Inc. All rights reserved.

Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial.

PubMed

Nalos, Marek; Leverve, Xavier; Huang, Stephen; Weisbrodt, Leonie; Parkin, Ray; Seppelt, Ian; Ting, Iris; Mclean, Anthony

2014-03-25

Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF. We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and (3) currently receiving vasopressor and/or inotropic support. Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The control group received only a 3 ml/kg bolus of Hartmann's solution without continuous infusion. The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation. Secondary outcomes included a measure of right ventricular systolic function (tricuspid annular plane systolic excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters, along with length of stay and mortality. The infusion of half-molar sodium lactate increased (mean ± SD) CO from 4.05 ± 1.37 L/min to 5.49 ± 1.9 L/min (P < 0.01) and TAPSE from 14.7 ± 5.5 mm to 18.3 ± 7 mm (P = 0.02). Plasma sodium and pH increased (136 ± 4 to 146 ± 6 and 7.40 ± 0.06 to 7.53 ± 0.03, respectively; both P < 0.01), but potassium, chloride and phosphate levels decreased. There were no significant differences in the need for vasoactive therapy, respiratory support, renal or liver function tests, duration of ICU and hospital stay or 28- and 90-day mortality. Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function. Clinicaltrials.gov NCT01981655. Registered 13 August 2013.

Inhaled hydrogen sulfide: a rapidly reversible inhibitor of cardiac and metabolic function in the mouse.

PubMed

Volpato, Gian Paolo; Searles, Robert; Yu, Binglan; Scherrer-Crosbie, Marielle; Bloch, Kenneth D; Ichinose, Fumito; Zapol, Warren M

2008-04-01

Breathing hydrogen sulfide (H2S) has been reported to induce a suspended animation-like state with hypothermia and a concomitant metabolic reduction in rodents. However, the impact of H2S breathing on cardiovascular function remains incompletely understood. In this study, the authors investigated the cardiovascular and metabolic effects of inhaled H2S in a murine model. The impact of breathing H2S on cardiovascular function was examined using telemetry and echocardiography in awake mice. The effects of breathing H2S on carbon dioxide production and oxygen consumption were measured at room temperature and in a warmed environment. Breathing H2S at 80 parts per million by volume at 27 degrees C ambient temperature for 6 h markedly reduced heart rate, core body temperature, respiratory rate, and physical activity, whereas blood pressure remained unchanged. Echocardiography demonstrated that H2S exposure decreased both heart rate and cardiac output but preserved stroke volume. Breathing H2S for 6 h at 35 degrees C ambient temperature (to prevent hypothermia) decreased heart rate, physical activity, respiratory rate, and cardiac output without altering stroke volume or body temperature. H2S breathing seems to induce bradycardia by depressing sinus node activity. Breathing H2S for 30 min decreased whole body oxygen consumption and carbon dioxide production at either 27 degrees or 35 degrees C ambient temperature. Both parameters returned to baseline levels within 10 min after the cessation of H2S breathing. Inhalation of H2S at either 27 degrees or 35 degrees C reversibly depresses cardiovascular function without changing blood pressure in mice. Breathing H2S also induces a rapidly reversible reduction of metabolic rate at either body temperature.

TRIIODOTHYRONINE INCREASES MYOCARDIAL FUNCTION AND PYRUVATE ENTRY INTO THE CITRIC ACID CYCLE AFTER REPERFUSION IN A MODEL OF INFANT CARDIOPULMONARY BYPASS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olson, Aaron; Bouchard, Bertrand; Ning, Xue-Han

We utilized a translational model of infant CPB to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC) thereby providing the energy support for improved cardiac function after ischemia-reperfusion. Methods and Results: Neonatal piglets received intracoronary [2-13Carbon(13C)]-pyruvate for 40 minutes (8 mM) during control aerobic conditions (Cont) or immediately after reperfusion (IR) from global hypothermic ischemia. A third group (IR-Tr) received T3 (1.2 ug/kg) during reperfusion. We assessed absolute CAC intermediate levels (aCAC) and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC ) and anaplerotic carboxylation (PC; ) using 13C-labeled pyruvate and isotopomermore » analysis by gas and liquid chromatography-mass spectrometry and 13C NMR. Neither IR nor IR-Tr modified aCAC. However, compared to IR, T3 (group IR-Tr) increased cardiac power and oxygen consumption after CPB while elevating both PDC and PC (~ four-fold). T3 inhibited IR induced reductions in CAC intermediate molar percent enrichment (MPE) and oxaloacetate(citrate)/malate MPE ratio; an index of aspartate entry into the CAC. Conclusions: T3 markedly enhances PC and PDC thereby providing substrate for elevated cardiac function and work after reperfusion. The increases in pyruvate flux occur with preservation of the CAC intermediate pool. Additionally, T3 inhibition of reductions in CAC intermediate MPEs indicates that T3 reduces the reliance on amino acids (AA) for anaplerosis after reperfusion. Thus, AA should be more available for other functions such as protein synthesis.« less

Detection of Early Right Ventricular Dysfunction in Young Patients With Thalassemia Major Using Tissue Doppler Imaging

PubMed Central

Bornaun, Helen; Dedeoglu, Reyhan; Oztarhan, Kazim; Dedeoglu, Savas; Erfidan, Erkan; Gundogdu, Muge; Aydogan, Gonul; Cengiz, Dicle

2016-01-01

Background Myocardial iron overload is the most common cause of mortality in patients with thalassemia major (TM), also known as beta-thalassemia. T2* cardiovascular magnetic resonance imaging (MRI) is the best way of monitoring cardiac iron, and new echocardiographic techniques can be used to assess cardiac function. Objectives The aim of this study was to assess the systolic and diastolic right ventricular (RV) function of patients with TM using tissue Doppler imaging (TDI) and to determine whether this echocardiographic technique is an adequate diagnostic tool for the screening and detection of subclinical cardiac dysfunction. Patients and Methods Eighty-four patients with TM were evaluated by conventional echocardiography and pulse-wave TDI. The data of the TM group (Group 1) were compared with that of 85 age- and sex-matched healthy controls (Group 2). Cardiovascular T2* MRI examinations were performed in 49 of the 85 patients. Results The patients with TM had significantly lower values for weight, height, body mass index, systolic arterial pressure, deceleration time, E’/A’, and ejection time (ET) than the controls. Group 1 also had significantly higher values for peak early diastolic velocity (E) over peak late diastolic velocity (A), peak early diastolic velocity of TDI (E’), peak late diastolic velocity of TDI (A’), E/E’, isovolumetric relaxation time, isovolumetric contraction time, and RV magnetic perfusion imaging (MPI) than Group 2. Conclusions RV diastolic dysfunction occurs before systolic deterioration in patients with TM and cannot be screened with conventional echocardiographic techniques. In routine practice, TDI measurements, MPI (for global function) and the E/E’ parameter (for diastolic function) can be used to screen and detect early RV dysfunction. PMID:27617076

Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

PubMed

Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

2018-02-14

Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

Clinical Profile of Cardiac Arrhythmias in Children Attending the Out Patient Department of a Tertiary Paediatric Care Centre in Chennai

PubMed Central

Sundararajan, Premkumar; Sangaralingam, Thangavelu

2016-01-01

Introduction The presentation of symptoms of paediatric arrhythmias vary depending on the age and underlying heart disease. Physical examination of children with important arrhythmias may be entirely normal. Aim Aim is to study the characteristics of cardiac arrhythmias in paediatric patients in a tertiary paediatric care centre in Chennai, India. Materials and Methods The participants (n=60) were from birth to 12 years of age. Patients with sinus arrhythmias, sinus tachycardia and sinus bradycardia were excluded. Proportions of various parameters of interest like clinical features, age and sex distribution and underlying heart disease of children presenting with cardiac arrhythmias were arrived. Statistical analysis was performed using SPSS version 16.0. Results Ventricular ectopics were the most common type of arrhythmias observed in the present study followed by Sinus Node Dysfunction (SND). The most common type of SND was sino atrial arrest. Supra ventricular tachycardia was the most frequently sustained tachyarrhythmia in the present study. An increased association of WPW (Wolf Parkinson White Syndrome) with specific congenital cardiac defects was noted. Conclusion Cardiac arrhythmias in children can present at anytime from fetal life to adolescence and their recognition requires high index of suspicion. While majority of children with arrhythmias have structurally normal heart, they are frequently encountered in children with underlying heart disease. Treatment of paediatric arrhythmias should be guided by the severity of the patient, the structure and function of the heart. PMID:28208963

A comparison study of atlas-based 3D cardiac MRI segmentation: global versus global and local transformations

NASA Astrophysics Data System (ADS)

Daryanani, Aditya; Dangi, Shusil; Ben-Zikri, Yehuda Kfir; Linte, Cristian A.

2016-03-01

Magnetic Resonance Imaging (MRI) is a standard-of-care imaging modality for cardiac function assessment and guidance of cardiac interventions thanks to its high image quality and lack of exposure to ionizing radiation. Cardiac health parameters such as left ventricular volume, ejection fraction, myocardial mass, thickness, and strain can be assessed by segmenting the heart from cardiac MRI images. Furthermore, the segmented pre-operative anatomical heart models can be used to precisely identify regions of interest to be treated during minimally invasive therapy. Hence, the use of accurate and computationally efficient segmentation techniques is critical, especially for intra-procedural guidance applications that rely on the peri-operative segmentation of subject-specific datasets without delaying the procedure workflow. Atlas-based segmentation incorporates prior knowledge of the anatomy of interest from expertly annotated image datasets. Typically, the ground truth atlas label is propagated to a test image using a combination of global and local registration. The high computational cost of non-rigid registration motivated us to obtain an initial segmentation using global transformations based on an atlas of the left ventricle from a population of patient MRI images and refine it using well developed technique based on graph cuts. Here we quantitatively compare the segmentations obtained from the global and global plus local atlases and refined using graph cut-based techniques with the expert segmentations according to several similarity metrics, including Dice correlation coefficient, Jaccard coefficient, Hausdorff distance, and Mean absolute distance error.

High-fat diet induces protein kinase A and G-protein receptor kinase phosphorylation of β2 -adrenergic receptor and impairs cardiac adrenergic reserve in animal hearts.

PubMed

Fu, Qin; Hu, Yuting; Wang, Qingtong; Liu, Yongming; Li, Ning; Xu, Bing; Kim, Sungjin; Chiamvimonvat, Nipavan; Xiang, Yang K

2017-03-15

Patients with diabetes show a blunted cardiac inotropic response to β-adrenergic stimulation despite normal cardiac contractile reserve. Acute insulin stimulation impairs β-adrenergically induced contractile function in isolated cardiomyocytes and Langendorff-perfused hearts. In this study, we aimed to examine the potential effects of hyperinsulinaemia associated with high-fat diet (HFD) feeding on the cardiac β 2 -adrenergic receptor signalling and the impacts on cardiac contractile function. We showed that 8 weeks of HFD feeding leads to reductions in cardiac functional reserve in response to β-adrenergic stimulation without significant alteration of cardiac structure and function, which is associated with significant changes in β 2 -adrenergic receptor phosphorylation at protein kinase A and G-protein receptor kinase sites in the myocardium. The results suggest that clinical intervention might be applied to subjects in early diabetes without cardiac symptoms to prevent further cardiac complications. Patients with diabetes display reduced exercise capability and impaired cardiac contractile reserve in response to adrenergic stimulation. We have recently uncovered an insulin receptor and adrenergic receptor signal network in the heart. The aim of this study was to understand the impacts of high-fat diet (HFD) on the insulin-adrenergic receptor signal network in hearts. After 8 weeks of HFD feeding, mice exhibited diabetes, with elevated insulin and glucose concentrations associated with body weight gain. Mice fed an HFD had normal cardiac structure and function. However, the HFD-fed mice displayed a significant elevation of phosphorylation of the β 2 -adrenergic receptor (β 2 AR) at both the protein kinase A site serine 261/262 and the G-protein-coupled receptor kinase site serine 355/356 and impaired adrenergic reserve when compared with mice fed on normal chow. Isolated myocytes from HFD-fed mice also displayed a reduced contractile response to adrenergic stimulation when compared with those of control mice fed normal chow. Genetic deletion of the β 2 AR led to a normalized adrenergic response and preserved cardiac contractile reserve in HFD-fed mice. Together, these data indicate that HFD promotes phosphorylation of the β 2 AR, contributing to impairment of cardiac contractile reserve before cardiac structural and functional remodelling, suggesting that early intervention in the insulin-adrenergic signalling network might be effective in prevention of cardiac complications in diabetes. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

High‐fat diet induces protein kinase A and G‐protein receptor kinase phosphorylation of β2‐adrenergic receptor and impairs cardiac adrenergic reserve in animal hearts

PubMed Central

Hu, Yuting; Wang, Qingtong; Liu, Yongming; Li, Ning; Xu, Bing; Kim, Sungjin; Chiamvimonvat, Nipavan

2017-01-01

Key points Patients with diabetes show a blunted cardiac inotropic response to β‐adrenergic stimulation despite normal cardiac contractile reserve.Acute insulin stimulation impairs β‐adrenergically induced contractile function in isolated cardiomyocytes and Langendorff‐perfused hearts.In this study, we aimed to examine the potential effects of hyperinsulinaemia associated with high‐fat diet (HFD) feeding on the cardiac β2‐adrenergic receptor signalling and the impacts on cardiac contractile function.We showed that 8 weeks of HFD feeding leads to reductions in cardiac functional reserve in response to β‐adrenergic stimulation without significant alteration of cardiac structure and function, which is associated with significant changes in β2‐adrenergic receptor phosphorylation at protein kinase A and G‐protein receptor kinase sites in the myocardium.The results suggest that clinical intervention might be applied to subjects in early diabetes without cardiac symptoms to prevent further cardiac complications. Abstract Patients with diabetes display reduced exercise capability and impaired cardiac contractile reserve in response to adrenergic stimulation. We have recently uncovered an insulin receptor and adrenergic receptor signal network in the heart. The aim of this study was to understand the impacts of high‐fat diet (HFD) on the insulin–adrenergic receptor signal network in hearts. After 8 weeks of HFD feeding, mice exhibited diabetes, with elevated insulin and glucose concentrations associated with body weight gain. Mice fed an HFD had normal cardiac structure and function. However, the HFD‐fed mice displayed a significant elevation of phosphorylation of the β2‐adrenergic receptor (β2AR) at both the protein kinase A site serine 261/262 and the G‐protein‐coupled receptor kinase site serine 355/356 and impaired adrenergic reserve when compared with mice fed on normal chow. Isolated myocytes from HFD‐fed mice also displayed a reduced contractile response to adrenergic stimulation when compared with those of control mice fed normal chow. Genetic deletion of the β2AR led to a normalized adrenergic response and preserved cardiac contractile reserve in HFD‐fed mice. Together, these data indicate that HFD promotes phosphorylation of the β2AR, contributing to impairment of cardiac contractile reserve before cardiac structural and functional remodelling, suggesting that early intervention in the insulin–adrenergic signalling network might be effective in prevention of cardiac complications in diabetes. PMID:27983752

Diastolic dysfunction characterizes cirrhotic cardiomyopathy

PubMed Central

Somani, Piyush O.; contractor, Qais; Chaurasia, Ajay S.; Rathi, Pravin M.

2014-01-01

Aim Present study aims to study the occurrence of cirrhotic cardiomyopathy and its correlation to hepatorenal syndrome by assessing the cardiac status in patients with cirrhosis of liver and healthy controls. Methods Thirty alcoholic cirrhotic, thirty non-alcoholic cirrhotic and thirty controls were enrolled for the study. Cardiac parameters were assessed by color doppler echocardiography. Patients were followed up for twelve months period for development of hepatorenal syndrome. Results Mild diastolic dysfunction was present in 18 cirrhotic patients (30%): grade I in fifteen patients and grade II in three. Diastolic dysfunction was unrelated to age; sex and etiology of cirrhosis. Among all the echocardiographic parameters, only deceleration time was found to be statistically significant. Echocardiographic parameters in systolic and diastolic function were not different in compensated vs decompensated patients in different Child-Pugh classes or cirrhosis aetiologies. At one year follow-up, no significant differences were found in survival between patients with or without diastolic dysfunction. Hepatorenal syndrome developed in only two patients and its correlation with diastolic dysfunction was not statistically significant. Conclusions Present study shows that although diastolic dysfunction is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There are no significant differences in echocardiographic parameters between alcoholic and non-alcoholic cirrhosis. HRS is not correlated to diastolic dysfunction in cirrhotic patients. There is no difference in survival at one year between patients with or without diastolic dysfunction. Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS. PMID:25634400

The influence of pericardial fat upon left ventricular function in obese females: evidence of a site-specific effect

PubMed Central

2014-01-01

Background Although increased volume of pericardial fat has been associated with decreased cardiac function, it is unclear whether this association is mediated by systemic overall obesity or direct regional fat interactions. We hypothesized that if local effects dominate, left ventricular (LV) function would be most strongly associated with pericardial fat that surrounds the left rather than the right ventricle (RV). Methods Female obese subjects (n = 60) had cardiovascular magnetic resonance (CMR) scans to obtain measures of LV function and pericardial fat volumes. LV function was obtained using the cine steady state free precession imaging in short axis orientation. The amount of pericardial fat was determined volumetrically by the cardiac gated T1 black blood imaging and normalized to body surface area. Results In this study cohort, LV fat correlated with several LV hemodynamic measurements including cardiac output (r = -0.41, p = 0.001) and stroke volume (r = -0.26, p = 0.05), as well as diastolic functional parameters including peak-early-filling rate (r = -0.38, p = 0.01), early late filling ratio (r = -0.34, p = 0.03), and time to peak-early-filling (r = 0.34, p = 0.03). These correlations remained significant even after adjusting for the body mass index and the blood pressure. However, similar correlations became weakened or even disappeared between RV fat and LV function. LV function was not correlated with systemic plasma factors, such as C-reactive protein (CRP), B-type natriuretic peptide (BNP), Interleukin-6 (IL-6), resistin and adiponectin (all p > 0.05). Conclusions LV hemodynamic and diastolic function was associated more with LV fat as compared to RV or total pericardial fat, but not with systemic inflammatory markers or adipokines. The correlations between LV function and pericardial fat remained significant even after adjusting for systemic factors. These findings suggest a site-specific influence of pericardial fat on LV function, which could imply local secretion of molecules into the underlying tissue or an anatomic effect, both mechanisms meriting future evaluation. PMID:24884541

Correlation between increased urinary sodium excretion and decreased left ventricular diastolic function in patients with type 2 diabetes mellitus.

PubMed

Kagiyama, Shuntaro; Koga, Tokushi; Kaseda, Shigeru; Ishihara, Shiro; Kawazoe, Nobuyuki; Sadoshima, Seizo; Matsumura, Kiyoshi; Takata, Yutaka; Tsuchihashi, Takuya; Iida, Mitsuo

2009-10-01

Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U-Na) in patients with DM. We measured 24-hour U-Na; cardiac function was evaluated directly during coronary catheterization in type 2 DM (n = 46) or non-DM (n = 55) patients with preserved cardiac systolic function (ejection fraction > or = 60%). Cardiac diastolic and systolic function was evaluated as - dp/dt and + dp/dt, respectively. The average of U-Na was 166.6 +/- 61.2 mEq/24 hour (mean +/- SD). In all patients, stepwise multivariate regression analysis revealed that - dp/dt had a negative correlation with serum B-type natriuretic peptide (BNP; beta = - 0.23, P = .021) and U-Na (beta = - 0.24, P = .013). On the other hand, + dp/dt negatively correlated with BNP (beta = - 0.30, P < .001), but did not relate to U-Na. In the DM-patients, stepwise multivariate regression analysis showed that - dp/dt still had a negative correlation with U-Na (beta = - 0.33, P = .025). The results indicated that increased urinary sodium excretion is associated with an impairment of cardiac diastolic function, especially in patients with DM, suggesting that a reduction of salt intake may improve cardiac diastolic function.

Fitting membrane resistance along with action potential shape in cardiac myocytes improves convergence: application of a multi-objective parallel genetic algorithm.

PubMed

Kaur, Jaspreet; Nygren, Anders; Vigmond, Edward J

2014-01-01

Fitting parameter sets of non-linear equations in cardiac single cell ionic models to reproduce experimental behavior is a time consuming process. The standard procedure is to adjust maximum channel conductances in ionic models to reproduce action potentials (APs) recorded in isolated cells. However, vastly different sets of parameters can produce similar APs. Furthermore, even with an excellent AP match in case of single cell, tissue behaviour may be very different. We hypothesize that this uncertainty can be reduced by additionally fitting membrane resistance (Rm). To investigate the importance of Rm, we developed a genetic algorithm approach which incorporated Rm data calculated at a few points in the cycle, in addition to AP morphology. Performance was compared to a genetic algorithm using only AP morphology data. The optimal parameter sets and goodness of fit as computed by the different methods were compared. First, we fit an ionic model to itself, starting from a random parameter set. Next, we fit the AP of one ionic model to that of another. Finally, we fit an ionic model to experimentally recorded rabbit action potentials. Adding the extra objective (Rm, at a few voltages) to the AP fit, lead to much better convergence. Typically, a smaller MSE (mean square error, defined as the average of the squared error between the target AP and AP that is to be fitted) was achieved in one fifth of the number of generations compared to using only AP data. Importantly, the variability in fit parameters was also greatly reduced, with many parameters showing an order of magnitude decrease in variability. Adding Rm to the objective function improves the robustness of fitting, better preserving tissue level behavior, and should be incorporated.

Systematic Characterization of the Murine Mitochondrial Proteome Using Functionally Validated Cardiac Mitochondria

PubMed Central

Zhang, Jun; Li, Xiaohai; Mueller, Michael; Wang, Yueju; Zong, Chenggong; Deng, Ning; Vondriska, Thomas M.; Liem, David A.; Yang, Jeong-In; Korge, Paavo; Honda, Henry; Weiss, James N.; Apweiler, Rolf; Ping, Peipei

2009-01-01

Mitochondria play essential roles in cardiac pathophysiology and the murine model has been extensively used to investigate cardiovascular diseases. In the present study, we characterized murine cardiac mitochondria using an LC/MS/MS approach. We extracted and purified cardiac mitochondria; validated their functionality to ensure the final preparation contains necessary components to sustain their normal function; and subjected these validated organelles to LC/MS/MS-based protein identification. A total of 940 distinct proteins were identified from murine cardiac mitochondria, among which, 480 proteins were not previously identified by major proteomic profiling studies. The 940 proteins consist of functional clusters known to support oxidative phosphorylation, metabolism and biogenesis. In addition, there are several other clusters--including proteolysis, protein folding, and reduction/oxidation signaling-which ostensibly represent previously under-appreciated tasks of cardiac mitochondria. Moreover, many identified proteins were found to occupy other subcellular locations, including cytoplasm, ER, and golgi, in addition to their presence in the mitochondria. These results provide a comprehensive picture of the murine cardiac mitochondrial proteome and underscore tissue- and species-specification. Moreover, the use of functionally intact mitochondria insures that the proteomic observations in this organelle are relevant to its normal biology and facilitates decoding the interplay between mitochondria and other organelles. PMID:18348319

Effects of Kaempferia parviflora Wall. Ex. Baker and sildenafil citrate on cGMP level, cardiac function, and intracellular Ca2+ regulation in rat hearts.

PubMed

Weerateerangkul, Punate; Palee, Siripong; Chinda, Kroekkiat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2012-09-01

Although Kaempferia parviflora extract (KPE) and its flavonoids have positive effects on the nitric oxide (NO) signaling pathway, its mechanisms on the heart are still unclear. Because our previous studies demonstrated that KPE decreased defibrillation efficacy in swine similar to that of sildenafil citrate, the phosphodiesterase-5 inhibitor, it is possible that KPE may affect the cardiac NO signaling pathway. In the present study, the effects of KPE and sildenafil citrate on cyclic guanosine monophosphate (cGMP) level, modulation of cardiac function, and Ca transients in ventricular myocytes were investigated. In a rat model, cardiac cGMP level, cardiac function, and Ca transients were measured before and after treatment with KPE and sildenafil citrate. KPE significantly increased the cGMP level and decreased cardiac function and Ca transient. These effects were similar to those found in the sildenafil citrate-treated group. Furthermore, the nonspecific NOS inhibitor could abolish the effects of KPE and sildenafil citrate on Ca transient. KPE has positive effect on NO signaling in the heart, resulting in an increased cGMP level, similar to that of sildenafil citrate. This effect was found to influence the physiology of normal heart via the attenuation of cardiac function and the reduction of Ca transient in ventricular myocytes.

Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression.

PubMed

Byrne, Nikole J; Levasseur, Jody; Sung, Miranda M; Masson, Grant; Boisvenue, Jamie; Young, Martin E; Dyck, Jason R B

2016-05-15

Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes. Male C57Bl/6 mice were subjected to either Sham or transverse aortic constriction (TAC) surgery to induce HF. After HF development, mice with severe HF (% ejection fraction < 30) underwent a second surgery to remove the aortic constriction (debanding, DB). Three weeks following DB, there was a near complete recovery of systolic and diastolic function, and gene expression of several markers for hypertrophy/HF were returned to values observed in healthy controls. Interestingly, pressure-overload-induced left ventricular hypertrophy (LVH) and cardiac substrate metabolism were restored at 1-week post-DB, which preceded functional recovery. The regression of severe HF is associated with early and dramatic improvements in cardiac energy metabolism and LVH normalization that precede restored cardiac function, suggesting that metabolic and structural improvements may be critical determinants for functional recovery. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Evaluation of cardiovascular risks of spaceflight does not support the NASA bioastronautics critical path roadmap.

PubMed

Convertino, Victor A; Cooke, William H

2005-09-01

Occurrence of serious cardiac dysrhythmias and diminished cardiac and vascular function are the primary cardiovascular risks of spaceflight identified in the 2005 NASA Bioastronautics Critical Path Roadmap. A review of the literature was conducted on experimental results and observational data obtained from spaceflight and relevant ground simulation studies that addressed occurrence of cardiac dysrhythmias, cardiac contractile and vascular function, manifestation of asymptomatic cardiovascular disease, orthostatic intolerance, and response to exercise stress. Based on data from astronauts who have flown in space, there is no compelling experimental evidence to support significant occurrence of cardiac dysrhythmias, manifestation of asymptomatic cardiovascular disease, or reduction in myocardial contractile function. Although there are post-spaceflight data that demonstrate lower peripheral resistance in astronauts who become presyncopal compared with non-presyncopal astronauts, it is not clear that these differences are the result of decreased vascular function. However, the evidence of postflight orthostatic intolerance and reduced exercise capacity is well substantiated by both spaceflight and ground experiments. Although attenuation of baroreflex function(s) may contribute to postflight orthostatic instability, a primary mechanism of orthostatic intolerance and reduced exercise capacity is reduced end-diastolic and stroke volume associated with lower blood volumes and consequent cardiac remodeling. Data from the literature on the current population of astronauts support the notion that the primary cardiovascular risks of spaceflight are compromised hemodynamic responses to central hypovolemia resulting in reduced orthostatic tolerance and exercise capacity rather than occurrence of cardiac dysrhythmias, reduced cardiac contractile and vascular function, or manifestation of asymptomatic cardiovascular disease. These observations warrant a critical review and revision of the 2005 Bioastronautics Critical Path Roadmap.

Abnormal cardiac autonomic regulation in mice lacking ASIC3.

PubMed

Cheng, Ching-Feng; Kuo, Terry B J; Chen, Wei-Nan; Lin, Chao-Chieh; Chen, Chih-Cheng

2014-01-01

Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3) is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3(-/-) mice. Asic3(-/-) mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3(-/-) mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3(-/-) mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

Mathematical Models of Cardiac Pacemaking Function

NASA Astrophysics Data System (ADS)

Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

2013-10-01

Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

Echocardiographic examinations of 60 African grey parrots and 30 other psittacine birds.

PubMed

Pees, M; Straub, J; Krautwald-Junghanns, M-E

2004-07-17

The aim of this study was to establish reference values for the assessment of cardiac function in birds by measuring structures in the heart of healthy psittacine birds; 60 grey parrots, 10 Amazon parrots, 10 cockatoos and 10 Senegal parrots were anaesthetised with isoflurane and examined echocardiographically. The heart was visualised in two planes (vertical and horizontal views). Depending on the quality of the images, several dimensions of the heart could be measured and various parameters calculated. On the basis of these values, it was possible to establish reference values for each parrot genus. Some relative parameters showed no significant difference between the genera, independent of the bird's size.

Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

NASA Astrophysics Data System (ADS)

Rogozhnikov, Dmitry; O'Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.

2016-12-01

There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

Balancing tissue perfusion demands: cardiovascular dynamics of Cancer magister during exposure to low salinity and hypoxia.

PubMed

McGaw, Iain J; McMahon, Brian R

2003-01-01

Decapod crustaceans inhabit aquatic environments that are frequently subjected to changes in salinity and oxygen content. The physiological responses of decapod crustaceans to either salinity or hypoxia are well documented; however, there are many fewer reports on the physiological responses during exposure to these parameters in combination. We investigated the effects of simultaneous and sequential combinations of low salinity and hypoxia on the cardiovascular physiology of the Dungeness crab, Cancer magister. Heart rate, as well as haemolymph flow rates through the anterolateral, hepatic, sternal and posterior arteries were measured using a pulsed-Doppler flowmeter. Summation of flows allowed calculation of cardiac output and division of this by heart rate yielded stroke volume. When hypoxia and low salinity were encountered simultaneously, the observed changes in cardiac properties tended to be a mix of both factors. Hypoxia caused a bradycardia, whereas exposure to low salinity was associated with a tachycardia. However, the hypoxic conditions had the dominant effect on heart rate. Although hypoxia caused an increase in stroke volume of the heart, the low salinity had a more pronounced effect, causing an overall decrease in stroke volume. The patterns of haemolymph flow through the arterial system also varied when hypoxia and low salinity were offered together. The resulting responses were a mix of those resulting from exposure to either parameter alone. When low salinity and hypoxia were offered sequentially, the parameter experienced first tended to have the dominant effect on cardiac function and haemolymph flows. Low salinity exposure was associated with an increase in heart rate, a decrease in stroke volume and cardiac output, and a concomitant decrease in haemolymph flow rates. Subsequent exposure to hypoxic conditions caused a slight decrease in rate, but other cardiovascular variables were largely unaffected. In contrast, when low salinity followed acclimation to hypoxic conditions, apart from an increased heart rate, there were no other cardiovascular changes associated with the low salinity episode. The implications of these changes in cardiovascular dynamics are discussed in relation to physiological mechanisms and the ecology of decapod crustaceans, in hypoxic or low salinity environments. Copyright 2003, Wiley-Liss, Inc.

HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation.

PubMed

Lin, Shenglan; Wang, Yana; Zhang, Xiaojin; Kong, Qiuyue; Li, Chuanfu; Li, Yuehua; Ding, Zhengnian; Liu, Li

2016-01-01

Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation.

The Role of Focused Echocardiography in Pediatric Intensive Care: A Critical Appraisal

PubMed Central

Gaspar, Heloisa Amaral; Morhy, Samira Saady

2015-01-01

Echocardiography is a key tool for hemodynamic assessment in Intensive Care Units (ICU). Focused echocardiography performed by nonspecialist physicians has a limited scope, and the most relevant parameters assessed by focused echocardiography in Pediatric ICU are left ventricular systolic function, fluid responsiveness, cardiac tamponade and pulmonary hypertension. Proper ability building of pediatric emergency care physicians and intensivists to perform focused echocardiography is feasible and provides improved care of severely ill children and thus should be encouraged. PMID:26605333

High-fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss.

PubMed

Zeng, Heng; Vaka, Venkata Ramana; He, Xiaochen; Booz, George W; Chen, Jian-Xiong

2015-08-01

Mitochondrial dysfunction plays an important role in obesity-induced cardiac impairment. SIRT3 is a mitochondrial protein associated with increased human life span and metabolism. This study investigated the functional role of SIRT3 in obesity-induced cardiac dysfunction. Wild-type (WT) and SIRT3 knockout (KO) mice were fed a normal diet (ND) or high-fat diet (HFD) for 16 weeks. Body weight, fasting glucose levels, reactive oxygen species (ROS) levels, myocardial capillary density, cardiac function and expression of hypoxia-inducible factor (HIF)-1α/-2α were assessed. HFD resulted in a significant reduction in SIRT3 expression in the heart. Both HFD and SIRT3 KO mice showed increased ROS formation, impaired HIF signalling and reduced capillary density in the heart. HFD induced cardiac hypertrophy and impaired cardiac function. SIRT3 KO mice fed HFD showed greater ROS production and a further reduction in cardiac function compared to SIRT3 KO mice on ND. Thus, the adverse effects of HFD on cardiac function were not attributable to SIRT3 loss alone. However, HFD did not further reduce capillary density in SIRT3 KO hearts, implicating SIRT3 loss in HFD-induced capillary rarefaction. Our study demonstrates the importance of SIRT3 in preserving heart function and capillary density in the setting of obesity. Thus, SIRT3 may be a potential therapeutic target for obesity-induced heart failure. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Cardiac mechanics: Physiological, clinical, and mathematical considerations

NASA Technical Reports Server (NTRS)

Mirsky, I. (Editor); Ghista, D. N.; Sandler, H.

1974-01-01

Recent studies concerning the basic physiological and biochemical principles underlying cardiac muscle contraction, methods for the assessment of cardiac function in the clinical situation, and mathematical approaches to cardiac mechanics are presented. Some of the topics covered include: cardiac ultrastructure and function in the normal and failing heart, myocardial energetics, clinical applications of angiocardiography, use of echocardiography for evaluating cardiac performance, systolic time intervals in the noninvasive assessment of left ventricular performance in man, evaluation of passive elastic stiffness for the left ventricle and isolated heart muscle, a conceptual model of myocardial infarction and cardiogenic shock, application of Huxley's sliding-filament theory to the mechanics of normal and hypertrophied cardiac muscle, and a rheological modeling of the intact left ventricle. Individual items are announced in this issue.

PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction

PubMed Central

Knight, Walter E.; Chen, Si; Zhang, Yishuai; Oikawa, Masayoshi; Wu, Meiping; Zhou, Qian; Miller, Clint L.; Cai, Yujun; Mickelsen, Deanne M.; Moravec, Christine; Small, Eric M.; Abe, Junichi; Yan, Chen

2016-01-01

Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β–stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance. PMID:27791092

Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

PubMed Central

Dietrich, Johannes W.; Müller, Patrick; Schiedat, Fabian; Schlömicher, Markus; Strauch, Justus; Chatzitomaris, Apostolos; Klein, Harald H.; Mügge, Andreas; Köhrle, Josef; Rijntjes, Eddy; Lehmphul, Ina

2015-01-01

Background Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. Methods Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5-diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. Results Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5-T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. Conclusion This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5-T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms. PMID:26279999

Similar efficacy from specific and non-specific mineralocorticoid receptor antagonist treatment of muscular dystrophy mice.

PubMed

Lowe, Jeovanna; Floyd, Kyle T; Rastogi, Neha; Schultz, Eric J; Chadwick, Jessica A; Swager, Sarah A; Zins, Jonathan G; Kadakia, Feni K; Smart, Suzanne; Gomez-Sanchez, Elise P; Gomez-Sanchez, Celso E; Raman, Subha V; Janssen, Paul M L; Rafael-Fortney, Jill A

2016-01-01

Combined treatment with an angiotensin-converting enzyme inhibitor and a mineralocorticoid receptor (MR) antagonist improved cardiac and skeletal muscle function and pathology in a mouse model of Duchenne muscular dystrophy. MR is present in limb and respiratory skeletal muscles and functions as a steroid hormone receptor. The goals of the current study were to compare the efficacy of the specific MR antagonist eplerenone with the non-specific MR antagonist spironolactone, both in combination with the angiotensin-converting enzyme inhibitor lisinopril. Three groups of n=18 dystrophin-deficient, utrophin-haploinsufficient male mice were given chow containing: lisinopril plus spironolactone, lisinopril plus eplerenone, or no drug, from four to 20 weeks-of-age. Eighteen C57BL/10 male mice were used as wild-type controls. In vivo measurements included cardiac magnetic resonance imaging, conscious electrocardiography, and grip strength. From each mouse in the study, diaphragm, extensor digitorum longus , and cardiac papillary muscle force was measured ex vivo , followed by histological quantification of muscle damage in heart, diaphragm, quadriceps, and abdominal muscles. MR protein levels were also verified in treated muscles. Treatment with specific and non-specific MR antagonists did not result in any adverse effects to dystrophic skeletal muscles or heart. Both treatments resulted in similar functional and pathological improvements across a wide array of parameters. MR protein levels were not reduced by treatment. These data suggest that spironolactone and eplerenone show similar effects in dystrophic mice and support the clinical development of MR antagonists for treating skeletal muscles in Duchenne muscular dystrophy.

Effect of Neurohormonal Blockade Drug Therapy on Outcomes and Left Ventricular Function and Structure After Left Ventricular Assist Device Implantation.

PubMed

Grupper, Avishay; Zhao, Yanjun M; Sajgalik, Pavol; Joyce, Lyle D; Park, Soon J; Pereira, Naveen L; Stulak, John M; Burnett, John C; Edwards, Brooks S; Daly, Richard C; Kushwaha, Sudhir S; Schirger, John A

2016-06-01

Neurohormonal blockade drug therapy (NHBDT) is the cornerstone therapy in heart failure (HF) management for promoting reverse cardiac remodeling and improving outcomes. It's utility in left ventricular assist device (LVAD) supported patients remains undefined. Sixty-four patients who received continuous flow LVAD at our institution were retrospectively reviewed and divided into 2 groups: no-NHBDT group (n = 33) received LVAD support only and NHBDT group (n = 31) received concurrent NHBDT based on the clinical judgment of the attending physicians. Cardiac remodeling (echocardiographic parameters and biomarkers) and clinical outcome (functional status, HF-related hospital readmissions, and mortality) data were collected. A statistically significant increase in ejection fraction, decrease in LV end-diastolic diameter index and LV mass index, and a sustained reduction in N-terminal pro B-type natriuretic peptide (NTproBNP) were observed in the NHBDT group at 6 months after LVAD implant (p <0.05). NHBDT-treated patients experienced significantly greater improvement in New York Heart Association functional classification and 6-minute-walk distance throughout the study. The combined end point of cardiovascular death or HF hospitalization was significantly reduced in patients receiving NHBDT (p = 0.013) associated primarily with a 12.1% absolute reduction in HF-related hospitalizations (p = 0.046). In conclusion, NHBDT in LVAD-supported patients is associated with a significant reversal in adverse cardiac remodeling and a reduction in morbidity and mortality compared with LVAD support alone. Copyright © 2016 Elsevier Inc. All rights reserved.

β-Arrestin2 Improves Post-Myocardial Infarction Heart Failure via Sarco(endo)plasmic Reticulum Ca2+-ATPase-Dependent Positive Inotropy in Cardiomyocytes.

PubMed

McCrink, Katie A; Maning, Jennifer; Vu, Angela; Jafferjee, Malika; Marrero, Christine; Brill, Ava; Bathgate-Siryk, Ashley; Dabul, Samalia; Koch, Walter J; Lymperopoulos, Anastasios

2017-11-01

Heart failure is the leading cause of death in the Western world, and new and innovative treatments are needed. The GPCR (G protein-coupled receptor) adapter proteins βarr (β-arrestin)-1 and βarr-2 are functionally distinct in the heart. βarr1 is cardiotoxic, decreasing contractility by opposing β 1 AR (adrenergic receptor) signaling and promoting apoptosis/inflammation post-myocardial infarction (MI). Conversely, βarr2 inhibits apoptosis/inflammation post-MI but its effects on cardiac function are not well understood. Herein, we sought to investigate whether βarr2 actually increases cardiac contractility. Via proteomic investigations in transgenic mouse hearts and in H9c2 rat cardiomyocytes, we have uncovered that βarr2 directly interacts with SERCA2a (sarco[endo]plasmic reticulum Ca 2+ -ATPase) in vivo and in vitro in a β 1 AR-dependent manner. This interaction causes acute SERCA2a SUMO (small ubiquitin-like modifier)-ylation, increasing SERCA2a activity and thus, cardiac contractility. βarr1 lacks this effect. Moreover, βarr2 does not desensitize β 1 AR cAMP-dependent procontractile signaling in cardiomyocytes, again contrary to βarr1. In vivo, post-MI heart failure mice overexpressing cardiac βarr2 have markedly improved cardiac function, apoptosis, inflammation, and adverse remodeling markers, as well as increased SERCA2a SUMOylation, levels, and activity, compared with control animals. Notably, βarr2 is capable of ameliorating cardiac function and remodeling post-MI despite not increasing cardiac βAR number or cAMP levels in vivo. In conclusion, enhancement of cardiac βarr2 levels/signaling via cardiac-specific gene transfer augments cardiac function safely, that is, while attenuating post-MI remodeling. Thus, cardiac βarr2 gene transfer might be a novel, safe positive inotropic therapy for both acute and chronic post-MI heart failure. © 2017 American Heart Association, Inc.

Yoga respiratory training improves respiratory function and cardiac sympathovagal balance in elderly subjects: a randomised controlled trial

PubMed Central

Santaella, Danilo F; Devesa, Cesar R S; Rojo, Marcos R; Amato, Marcelo B P; Drager, Luciano F; Casali, Karina R; Montano, Nicola

2011-01-01

Objectives Since ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects. Design 76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68±6 years, 34% males, body mass index 25±3 kg/m2). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months. Results Subjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PEmax (34%, p<0.0001) and PImax (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group. Conclusion Respiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance. Trial Registration CinicalTrials.gov identifier: NCT00969345; trial registry name: Effects of respiratory yoga training (Bhastrika) on heart rate variability and baroreflex, and quality of life of healthy elderly subjects. PMID:22021757

Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

PubMed

Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

2015-04-01

Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

Morpho-functional assessment of interatrial septum: a transesophageal echocardiographic study.

PubMed

Galzerano, D; Tuccillo, B; Lama, D; Paolisso, G; Mirra, G; Giasi, M

1995-08-01

Despite the increasing number of reports on lipomatous hypertrophy of interatrial septum, a standardization of measurement of the dimensions of the interatrial septum (IAS) in the different phases of cardiac cycle has not been reported. Moreover, no data on modification of thickness with age and in specific cardiac diseases are available. Our purpose was to study whether the changes of thickness and thinning of IAS may be related to age, left atrial dimension, cardiac cycle and different cardiac diseases. 248 patients (mean age 52.7 +/- 19.9 years) underwent transthoracic (TTE) and transesophageal (TEE) echocardiography. IAS was measured at the constant regions anterior and posterior to the fossa ovalis. IAS thickness (tk), thinning (th) and % thinning (% th) were measured. IAS thickness ranged from 4 to 13 mm at the time of ventricular end-systolic phase (mean 6.7 +/- 1.9 mm) and from 6 to 16 mm at the time of atrial systole (mean 9.9 +/- 1.8 mm); significant statistical difference between these values was found (P < 0.01). IAS thinning ranged from 1 to 7 mm (mean 3.42 +/- 1.8) while % IAS thinning from 18 to 76% (mean 36.53 +/- 16.36%). Statistical analysis showed a significant positive correlation between age and ventricular end-systolic thickness and atrial systolic thickness and thinning. An insignificant correlation was found between age and % IAS thinning and between left atrial dimension and IAS tk and th. Our results demonstrate that IAS thickness increases by age; no correlation exists between IAS thinning and age. There is no difference between IAS thickness and thinning in patients with or without cardiac disease. We believe that the thickness of IAS can be considered hypertrophic only if it exceeds the value of 15 mm during both ventricular end-systolic and atrial systolic phases of the cardiac cycle. IAS thickness and thinning might be an additional parameter to evaluate systolic atrial function particularly with regard to maintenance of synus rhythm after conversion from atrial fibrillation as well as to better understand its role in determining the filling of ventricles in different clinical conditions.

The Oscillating Component of the Internal Jugular Vein Flow: The Overlooked Element of Cerebral Circulation

PubMed Central

Sisini, Francesco; Toro, Eleuterio; Gambaccini, Mauro; Zamboni, Paolo

2015-01-01

The jugular venous pulse (JVP) provides valuable information about cardiac haemodynamics and filling pressures and is an indirect estimate of the central venous pressure (CVP). Recently it has been proven that JVP can be obtained by measuring the cross-sectional area (CSA) of the IJV on each sonogram of an ultrasound B-mode sonogram sequence. It has also been proven that during its pulsation the IJV is distended and hence that the pressure gradient drives the IJV haemodynamics. If this is true, then it will imply the following: (i) the blood velocity in the IJV is a periodic function of the time with period equal to the cardiac period and (ii) the instantaneous blood velocity is given by a time function that can be derived from a flow-dynamics theory that uses the instantaneous pressure gradient as a parameter. The aim of the present study is to confirm the hypothesis that JVP regulates the IJV blood flow and that pressure waves are transmitted from the heart toward the brain through the IJV wall. PMID:26783380

MitoQ administration prevents endotoxin-induced cardiac dysfunction

PubMed Central

Murphy, M. P.; Callahan, L. A.

2009-01-01

Sepsis elicits severe alterations in cardiac function, impairing cardiac mitochondrial and pressure-generating capacity. Currently, there are no therapies to prevent sepsis-induced cardiac dysfunction. We tested the hypothesis that administration of a mitochondrially targeted antioxidant, 10-(6′-ubiquinonyl)-decyltriphenylphosphonium (MitoQ), would prevent endotoxin-induced reductions in cardiac mitochondrial and contractile function. Studies were performed on adult rodents (n = 52) given either saline, endotoxin (8 mg·kg−1·day−1), saline + MitoQ (500 μM), or both endotoxin and MitoQ. At 48 h animals were killed and hearts were removed for determination of either cardiac mitochondrial function (using polarography) or cardiac pressure generation (using the Langendorf technique). We found that endotoxin induced reductions in mitochondrial state 3 respiration rates, the respiratory control ratio, and ATP generation. Moreover, MitoQ administration prevented each of these endotoxin-induced abnormalities, P < 0.001. We also found that endotoxin produced reductions in cardiac pressure-generating capacity, reducing the systolic pressure-diastolic relationship. MitoQ also prevented endotoxin-induced reductions in cardiac pressure generation, P < 0.01. One potential link between mitochondrial and contractile dysfunction is caspase activation; we found that endotoxin increased cardiac levels of active caspases 9 and 3 (P < 0.001), while MitoQ prevented this increase (P < 0.01). These data demonstrate that MitoQ is a potent inhibitor of endotoxin-induced mitochondrial and cardiac abnormalities. We speculate that this agent may prove a novel therapy for sepsis-induced cardiac dysfunction. PMID:19657095

MitoQ administration prevents endotoxin-induced cardiac dysfunction.

PubMed

Supinski, G S; Murphy, M P; Callahan, L A

2009-10-01

Sepsis elicits severe alterations in cardiac function, impairing cardiac mitochondrial and pressure-generating capacity. Currently, there are no therapies to prevent sepsis-induced cardiac dysfunction. We tested the hypothesis that administration of a mitochondrially targeted antioxidant, 10-(6'-ubiquinonyl)-decyltriphenylphosphonium (MitoQ), would prevent endotoxin-induced reductions in cardiac mitochondrial and contractile function. Studies were performed on adult rodents (n = 52) given either saline, endotoxin (8 mg x kg(-1) x day(-1)), saline + MitoQ (500 microM), or both endotoxin and MitoQ. At 48 h animals were killed and hearts were removed for determination of either cardiac mitochondrial function (using polarography) or cardiac pressure generation (using the Langendorf technique). We found that endotoxin induced reductions in mitochondrial state 3 respiration rates, the respiratory control ratio, and ATP generation. Moreover, MitoQ administration prevented each of these endotoxin-induced abnormalities, P < 0.001. We also found that endotoxin produced reductions in cardiac pressure-generating capacity, reducing the systolic pressure-diastolic relationship. MitoQ also prevented endotoxin-induced reductions in cardiac pressure generation, P < 0.01. One potential link between mitochondrial and contractile dysfunction is caspase activation; we found that endotoxin increased cardiac levels of active caspases 9 and 3 (P < 0.001), while MitoQ prevented this increase (P < 0.01). These data demonstrate that MitoQ is a potent inhibitor of endotoxin-induced mitochondrial and cardiac abnormalities. We speculate that this agent may prove a novel therapy for sepsis-induced cardiac dysfunction.

SCN5A (NaV1.5) Variant Functional Perturbation and Clinical Presentation: Variants of a Certain Significance.

PubMed

Kroncke, Brett M; Glazer, Andrew M; Smith, Derek K; Blume, Jeffrey D; Roden, Dan M

2018-05-01

Accurately predicting the impact of rare nonsynonymous variants on disease risk is an important goal in precision medicine. Variants in the cardiac sodium channel SCN5A (protein Na V 1.5; voltage-dependent cardiac Na+ channel) are associated with multiple arrhythmia disorders, including Brugada syndrome and long QT syndrome. Rare SCN5A variants also occur in ≈1% of unaffected individuals. We hypothesized that in vitro electrophysiological functional parameters explain a statistically significant portion of the variability in disease penetrance. From a comprehensive literature review, we quantified the number of carriers presenting with and without disease for 1712 reported SCN5A variants. For 356 variants, data were also available for 5 Na V 1.5 electrophysiological parameters: peak current, late/persistent current, steady-state V1/2 of activation and inactivation, and recovery from inactivation. We found that peak and late current significantly associate with Brugada syndrome ( P <0.001; ρ=-0.44; Spearman rank test) and long QT syndrome disease penetrance ( P <0.001; ρ=0.37). Steady-state V1/2 activation and recovery from inactivation associate significantly with Brugada syndrome and long QT syndrome penetrance, respectively. Continuous estimates of disease penetrance align with the current American College of Medical Genetics classification paradigm. Na V 1.5 in vitro electrophysiological parameters are correlated with Brugada syndrome and long QT syndrome disease risk. Our data emphasize the value of in vitro electrophysiological characterization and incorporating counts of affected and unaffected carriers to aid variant classification. This quantitative analysis of the electrophysiological literature should aid the interpretation of Na V 1.5 variant electrophysiological abnormalities and help improve Na V 1.5 variant classification. © 2018 American Heart Association, Inc.

Effects of a one-week vacation with various activity programs on cardiovascular parameters.

PubMed

Neumayr, Günther; Lechleitner, Peter

2018-03-01

A vacation is considered essential to achieve recovery from the stress of work. Knowledge about the potential health effects of holidays is scarce. The East Tyrolean Health Tourism Study is an open comparative study to investigate the cardiovascular effects of a one- week vacation with different activities on healthy vacationers. Fifty-two healthy vacationers spending one week in East Tyrol participated in two types of vacation activities (golf vs. Nordic walking or e-biking [nw&eb]). In the former group 30 subjects played golf for 33.5 hours per week, and in the nw&eb group 22 engaged in Nordic walking or e-biking for 14.2 hours per week. Cardiovascular parameters such as performance capacity, blood pressure, heart rate profiles and cardiac diastolic function were measured by a cardiopulmonary exercise test, holter ECG and echocardiography performed one day before and after the stay. There was a significant decrease in body weight of 1.0 kg in the nw&eb-group but not in the golf group. In both groups we noted a reduction of blood pressure and heart rate, which was marked and significant only in the golf group. We observed no significant changes in performance capacity, but did note an improvement of cardiac diastolic function in both groups; the improvement was more pronounced in the nw&eb group. A one-week vacation with an activity program for several hours per week is well tolerated by healthy vacationers and improves cardiovascular parameters. The cardiovascular benefits were homogeneous but differed in their magnitude, depending on the activity group. The benefits were probably due to the enhanced physical activity rather than purely a holiday effect.

Induced hypothermia does not impair coagulation system in a swine multiple trauma model.

PubMed

Mohr, Juliane; Ruchholtz, Steffen; Hildebrand, Frank; Flohé, Sascha; Frink, Michael; Witte, Ingo; Weuster, Matthias; Fröhlich, Matthias; van Griensven, Martijn; Keibl, Claudia; Mommsen, Philipp

2013-04-01

Accidental hypothermia, acidosis, and coagulopathy represent the lethal triad in severely injured patients. Therapeutic hypothermia however is commonly used in transplantations, cardiac and neurosurgical surgery, or after cardiac arrest. However, the effects of therapeutic hypothermia on the coagulation system following multiple trauma need to be elucidated. In a porcine model of multiple trauma including blunt chest injury, liver laceration, and hemorrhagic shock followed by fluid resuscitation, the influence of therapeutic hypothermia on coagulation was evaluated. A total of 40 pigs were randomly assigned to sham (only anesthesia) or trauma groups receiving either hypothermia or normothermia. Each group consisted of 10 pigs. Analyzed parameters were cell count (red blood cells, platelets), pH, prothrombin time (PT), fibrinogen concentration, and analysis with ROTEM and Multiplate. Trauma and consecutive fluid resuscitation resulted in impaired coagulation parameters (cell count, pH, PT, fibrinogen, ROTEM, and platelet function). During hypothermia, coagulation parameters measured at 37°C, such as PT, fibrinogen, thrombelastometry measurements, and platelet function, showed no significant differences between normothermic and hypothermic animals in both trauma groups. Additional analyses of thrombelastometry at 34°C during hypothermia showed significant differences for clotting time and clot formation time but not for maximum clot firmness. We were not able to detect macroscopic or petechial bleeding in both trauma groups. Based on the results of the present study we suggest that mild hypothermia can be safely performed after stabilization following major trauma. Mild hypothermia has effects on the coagulation system but does not aggravate trauma-induced coagulopathy in our model. Before hypothermic treatment can be performed in the clinical setting, additional experiments with prolonged and deeper hypothermia to exclude detrimental effects are required.

Functional role of AMP-activated protein kinase in the heart during exercise.

PubMed

Musi, Nicolas; Hirshman, Michael F; Arad, Michael; Xing, Yanqiu; Fujii, Nobuharu; Pomerleau, Jason; Ahmad, Ferhaan; Berul, Charles I; Seidman, Jon G; Tian, Rong; Goodyear, Laurie J

2005-04-11

AMP-activated protein kinase (AMPK) plays a critical role in maintaining energy homeostasis and cardiac function during ischemia in the heart. However, the functional role of AMPK in the heart during exercise is unknown. We examined whether acute exercise increases AMPK activity in mouse hearts and determined the significance of these increases by studying transgenic (TG) mice expressing a cardiac-specific dominant-negative (inactivating) AMPKalpha2 subunit. Exercise increased cardiac AMPKalpha2 activity in the wild type mice but not in TG. We found that inactivation of AMPK did not result in abnormal ATP and glycogen consumption during exercise, cardiac function assessed by heart rhythm telemetry and stress echocardiography, or in maximal exercise capacity.

Cardiac and autonomic nerve function after reduced-intensity stem cell transplantation for hematologic malignancy in patients with pre-transplant cardiac dysfunction.

PubMed

Nakane, Takahiko; Nakamae, Hirohisa; Muro, Takashi; Yamagishi, Hiroyuki; Kobayashi, Yoshiki; Aimoto, Mizuki; Sakamoto, Erina; Terada, Yoshiki; Nakamae, Mika; Koh, Ki-Ryang; Yamane, Takahisa; Yoshiyama, Minoru; Hino, Masayuki

2009-09-01

Recent reports have shown that cardiomyopathy caused by hemochromatosis in severe aplastic anemia is reversible after reduced-intensity allogeneic stem-cell transplantation (RIST). We comprehensively evaluated cardiac and autonomic nerve function to determine whether cardiac dysfunction due to causes other than hemochromatosis is attenuated after RIST. In five patients with cardiac dysfunction before transplant, we analyzed the changes in cardiac and autonomic nerve function after transplant, using electrocardiography (ECG), echocardiography, radionuclide angiography (RNA), serum markers, and heart rate variability (HRV), before and up to 100 days after transplant. There was no significant improvement in cardiac function in any patient and no significant alteration in ECG, echocardiogram, RNA, or serum markers. However, on time-domain analysis of HRV, the SD of normal-to-normal RR intervals (SDNN) and the coefficient of variation of the RR interval (CVRR) decreased significantly 30 and 60 days after transplant (P = 0.04 and 0.01, respectively). Similarly, on frequency-domain analysis of HRV, low and high frequency power (LF and HF) significantly and temporarily decreased (P = 0.003 and 0.03, respectively). Notably, in one patient who had acute heart failure after transplantation, the values of SDNN, CVRR, r-MSSD, LF, and HF at 30 and 60 days after transplantation were the lowest of all the patients. In conclusion, this study suggests that (a) RIST is well-tolerated in patients with cardiac dysfunction, but we cannot expect improvement in cardiac dysfunction due to causes other than hemochromatosis; and (b) monitoring HRV may be useful in predicting cardiac events after RIST.

Association of segmental wall motion abnormalities occurring during hemodialysis with post-dialysis fatigue.

PubMed

Dubin, Ruth F; Teerlink, John R; Schiller, Nelson B; Alokozai, Dean; Peralta, Carmen A; Johansen, Kirsten L

2013-10-01

Post-dialysis fatigue (PDF) is a common, debilitating symptom that remains poorly understood. Cardiac wall motion abnormalities (WMAs) may worsen during dialysis, but it is unknown whether WMA are associated with PDF. Forty patients were recruited from University of California San Francisco-affiliated dialysis units between January 2010 and February 2011. Participants underwent echocardiograms before and during the last hour of 79 dialysis sessions. Myocardial segments were graded 1-4 by a blinded reviewer, with four representing the worst WMA, and the segmental scores were summed for each echocardiogram. Patients completed questionnaires about their symptoms. Severe PDF (defined as lasting >2 h after dialysis) was analysed using a generalized linear model with candidate predictors including anemia, intradialytic hemodynamics and cardiac function. Forty-four percent of patients with worsened WMA (n=9) had severe PDF, compared with 13% of patients with improved or unchanged WMA (P = 0.04). A one-point increase in the WMA score during dialysis was associated with a 10% higher RR of severe PDF [RR: 1.1, 95% CI (1.1, 1.2), P < 0.001]. After multivariable adjustment, every point increase in the WMA score was associated with a 2-fold higher risk of severe PDF [RR: 1.9, 95% CI (1.4, 2.6), P < 0.001]. History of depression was associated with severe PDF after adjustment for demographics and comorbidities [RR: 3.4, 95% CI (1.3, 9), P = 0.01], but anemia, hemodynamics and other parameters of cardiac function were not. Although cross-sectional, these results suggest that some patients may experience severe PDF as a symptom of cardiac ischemia occurring during dialysis.