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.

Cardiac Impairment Evaluated by Transesophageal Echocardiography and Invasive Measurements in Rats Undergoing Sinoaortic Denervation

PubMed Central

Sirvente, Raquel A.; Irigoyen, Maria C.; Souza, Leandro E.; Mostarda, Cristiano; La Fuente, Raquel N.; Candido, Georgia O.; Souza, Pamella R. M.; Medeiros, Alessandra; Mady, Charles; Salemi, Vera M. C.

2014-01-01

Background Sympathetic hyperactivity may be related to left ventricular (LV) dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE) using intracardiac echocardiographic catheter. Methods and Results We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD). The rats (n = 32) were divided into 4 groups: 16 Wistar (W) with (n = 8) or without SAD (n = 8) and 16 spontaneously hypertensive rats (SHR) with (n = 8) or without SAD (SHRSAD) (n = 8). Blood pressure (BP) and heart rate (HR) did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV) concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV) pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. Conclusions Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease. PMID:24828834

Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

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

Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Talbert, Dominique R.; Trusk, Patricia B.

Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks.more » Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in-depth insight towards mechanism of cardiac toxicity. • Testing functional and structural endpoints enhances early cardiac risk assessment.« less

Adenosine triphosphate postconditioning is associated with better preserved global and regional cardiac function during myocardial ischemia and reperfusion: a speckle tracking imaging-based echocardiologic study.

PubMed

Ren, Min; Liu, Yujie; Zhao, Huiya; Dong, Shixia; Jiang, Zhonghui; Li, Keting; Tian, Jiawei

2016-10-01

Effects of ischemic postconditioning (IPostC) and adenosine triphosphate (ATP)-mediated pharmacologic postconditioning (ATP-PPostC) on cardiac function were evaluated by speckle tracking imaging (STI)-based echocardiography. A myocardial I/R model was induced in rabbits by reversible ligation of the left ventricular branch of coronary artery. Rabbits were randomized into three groups: ischemia and reperfusion (IR) (no further intervention), IPostC, and ATP-PPostC groups. Cardiac function was evaluated by conventional and STI-based echocardiography. Myocardial necrosis, apoptosis, and myocardial mRNAs of apoptosis-related proteins (Bcl-2 and Bax) were evaluated. Speckle tracking imaging (STI)-based echocardiography revealed that IPostC and ATP-PPostC were associated with better preserved global and regional cardiac function, as indicated by significantly increased GLSrsys, GLSrd, GLSsys, SrLsys, SrLd, and SLsys in both groups (all P<.5). Subsequent pathologic studies indicate that the percentage of necrotic myocardium and permillage of apoptotic cells were significantly lower in the IPostC and ATP-PPostC groups than in the IR group (all P<.05). Moreover, both IPostC and ATP-PPostC were associated with increased Bcl-2 mRNA levels and reduced Bax mRNA levels. IPostC and ATP-PPostC may exert cardioprotective functions by better preservation of cardiac function during the I/R process and at least partly via attenuation of myocardial apoptosis. © 2016 John Wiley & Sons Ltd.

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.

A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

EPA Science Inventory

Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

Cardiac fluid dynamics meets deformation imaging.

PubMed

Dal Ferro, Matteo; Stolfo, Davide; De Paris, Valerio; Lesizza, Pierluigi; Korcova, Renata; Collia, Dario; Tonti, Giovanni; Sinagra, Gianfranco; Pedrizzetti, Gianni

2018-02-20

Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.

Sympathetic- and Parasympathetic-Linked Cardiac Function and Prediction of Externalizing Behavior, Emotion Regulation, and Prosocial Behavior among Preschoolers Treated for ADHD

ERIC Educational Resources Information Center

Beauchaine, Theodore P.; Gatzke-Kopp, Lisa; Neuhaus, Emily; Chipman, Jane; Reid, M. Jamila; Webster-Stratton, Carolyn

2013-01-01

Objective: To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). Method: Cardiac preejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia…

Nuclear cardiac

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

Slutsky, R.; Ashburn, W.L.

1982-01-01

The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques. (KRM)

Inhibition of Oct 3/4 mitigates the cardiac progenitor-derived myocardial repair in infarcted myocardium.

PubMed

Zhao, Yu Tina; Du, Jianfeng; Chen, Youfang; Tang, Yaoliang; Qin, Gangjian; Lv, Guorong; Zhuang, Shougang; Zhao, Ting C

2015-12-24

Recent evidence has demonstrated that cardiac progenitor cells play an essential role in the induction of angiomyogenesis in infarcted myocardium. We and others have shown that engraftment of c-kit(+) cardiac stem cells (CSCs) into infarcted hearts led to myocardium regeneration and neovascularization, which was associated with an improvement of ventricular function. The purpose of this study is aimed at investigating the functional role of transcription factor (TF) Oct3/4 in facilitating CSCs to promote myocardium regeneration and preserve cardiac performance in the post-MI heart. c-kit(+) CSCs were isolated from adult hearts and re-introduced into the infarcted myocardium in which the mouse MI model was created by permanent ligation of the left anterior descending artery (LAD). The Oct3/4 of CSCs was inhibited by transfection of Oct3/4 siRNA, and transfection of CSCs with control siRNA serves as control groups. Myocardial functions were evaluated by echocardiographic measurement. Histological analysis was employed to assess newly formed cardiogenesis, neovascularization, and cell proliferations. Terminal deoxynucleotidyltransferase (TdT) nick-end labeling (TUNEL) was carried out to assess apoptotic cardiomyocytes. Real time polymerase chain reaction and Western blot were carried out to evaluate the level of Oct 3/4 in CSCs. Two weeks after engraftment, CSCs increased ventricular functional recovery as shown by a serial echocardiographic measurement, which is concomitant with the suppression of cardiac hypertrophy and attenuation of myocardial interstitial fibrosis. Suppression of Oct 3/4 of CSCs abrogated functional improvements and mitigated the hypertrophic response and cardiac remodeling. Transplantation of c-kit(+) CSCs into MI hearts promoted cardiac regeneration and neovascularization, which were abolished with the knockdown of Oct3/4. Additionally, suppression of Oct3/4 abrogated myocyte proliferation in the CSC-engrafted myocardium. Our results indicate that CSCs-derived cardiac regeneration improves the restoration of cardiac function and is mediated through Oct 3/4.

Evaluation of platelet function in dogs with cardiac disease using the PFA-100 platelet function analyzer.

PubMed

Clancey, Noel; Burton, Shelley; Horney, Barbara; Mackenzie, Allan; Nicastro, Andrea; Côté, Etienne

2009-09-01

Cardiac disease has the potential to alter platelet function in dogs. Evaluation of platelet function using the PFA-100 analyzer in dogs of multiple breeds and with a broad range of cardiac conditions would help clarify the effect of cardiac disease on platelets. The objective of this study was to assess differences in closure time (CT) in dogs with cardiac disease associated with murmurs, when compared with that of healthy dogs. Thirty-nine dogs with cardiac murmurs and turbulent blood flow as determined echocardiographically were included in the study. The dogs represented 23 different breeds. Dogs with murmurs were further divided into those with atrioventricular valvular insufficiency (n=23) and subaortic stenosis (n=9). Fifty-eight clinically healthy dogs were used as controls. CTs were determined in duplicate on a PFA-100 analyzer using collagen/ADP cartridges. Compared with CTs in the control group (mean+/-SD, 57.6+/-5.9 seconds; median, 56.5 seconds; reference interval, 48.0-77.0 seconds), dogs with valvular insufficiency (mean+/-SD, 81.9+/-26.3 seconds; median, 78.0 seconds; range, 52.5-187 seconds), subaortic stenosis (71.4+/-16.5 seconds; median, 66.0 seconds; range, 51.5-95.0 seconds), and all dogs with murmurs combined (79.6+/-24.1 seconds; median, 74.0 seconds; range, 48.0-187 seconds) had significantly prolonged CTs (P<.01). The PFA-100 analyzer is useful in detecting platelet function defects in dogs with cardiac murmurs, most notably those caused by mitral and/or tricuspid valvular insufficiency or subaortic stenosis. The form of turbulent blood flow does not appear to be an important factor in platelet hypofunction in these forms of cardiac disease.

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.

Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy.

PubMed

Beer, Meinrad; Weidemann, Frank; Breunig, Frank; Knoll, Anita; Koeppe, Sabrina; Machann, Wolfram; Hahn, Dietbert; Wanner, Christoph; Strotmann, Jörg; Sandstede, Jörn

2006-05-15

The present study evaluated the evolution of cardiac morphology, function, and late enhancement as a noninvasive marker of myocardial fibrosis, and their inter-relation during enzyme replacement therapy in patients with Fabry's disease using magnetic resonance imaging and color Doppler myocardial imaging. Late enhancement, which was present in up to 50% of patients, was associated with increased left ventricular mass, the failure of a significant regression of hypertrophy during enzyme replacement therapy, and worse segmental myocardial function. Late enhancement may predict the effect of enzyme replacement therapy on left ventricular mass and cardiac function.

Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase.

PubMed

Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

2016-01-01

To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery.

Hammersmith cardiology workshop series. Volume 2

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

Maseri, A.

1985-01-01

This book contains over 30 selections. Some of the titles are: Digital Subtraction Angiography: The Optimal Radiologic Technique for Cardiac Diagnosis; NMR Imaging of the Heart; Radioisotopes in the Evaluation of Right and Left Ventricular Function; Role of Membrane Abnormalities in the Pathogenesis of Heart Disease; and Influence of Arrhythmias on Cardiac Function.

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.

Cardiac dysfunction in the diabetic rat: quantitative evaluation using high resolution magnetic resonance imaging.

PubMed

Loganathan, Rajprasad; Bilgen, Mehmet; Al-Hafez, Baraa; Alenezy, Mohammed D; Smirnova, Irina V

2006-04-04

Diabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy. In this study, we used high field magnetic resonance imaging (MRI) to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched controls. Our analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively) compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats. Thus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes.

Pain-related somatosensory evoked potentials and functional brain magnetic resonance in the evaluation of neurologic recovery after cardiac arrest: a case study of three patients.

PubMed

Zanatta, Paolo; Messerotti Benvenuti, Simone; Baldanzi, Fabrizio; Bendini, Matteo; Saccavini, Marsilio; Tamari, Wadih; Palomba, Daniela; Bosco, Enrico

2012-03-31

This case series investigates whether painful electrical stimulation increases the early prognostic value of both somatosensory-evoked potentials and functional magnetic resonance imaging in comatose patients after cardiac arrest. Three single cases with hypoxic-ischemic encephalopathy were considered. A neurophysiological evaluation with an electroencephalogram and somatosensory-evoked potentials during increased electrical stimulation in both median nerves was performed within five days of cardiac arrest. Each patient also underwent a functional magnetic resonance imaging evaluation with the same neurophysiological protocol one month after cardiac arrest. One patient, who completely recovered, showed a middle latency component at a high intensity of stimulation and the activation of all brain areas involved in cerebral pain processing. One patient in a minimally conscious state only showed the cortical somatosensory response and the activation of the primary somatosensory cortex. The last patient, who was in a vegetative state, did not show primary somatosensory evoked potentials; only the activation of subcortical brain areas occurred. These preliminary findings suggest that the pain-related somatosensory evoked potentials performed to increase the prognosis of comatose patients after cardiac arrest are associated with regional brain activity showed by functional magnetic resonance imaging during median nerves electrical stimulation. More importantly, this cases report also suggests that somatosensory evoked potentials and functional magnetic resonance imaging during painful electrical stimulation may be sensitive and complementary methods to predict the neurological outcome in the acute phase of coma. Thus, pain-related somatosensory-evoked potentials may be a reliable and a cost-effective tool for planning the early diagnostic evaluation of comatose patients.

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.

Hypothyroidism-induced myocardial damage and heart failure: an overlooked entity.

PubMed

Shuvy, Mony; Shifman, Oshrat E Tayer; Nusair, Samir; Pappo, Orit; Lotan, Chaim

2009-01-01

Hypothyroid state may induce cardiac muscle impairment such as diastolic dysfunction and abnormal relaxation time. Advanced heart failure in hypothyroid patients has been described only in severe symptomatic cases, mostly during myxedematous coma. We describe an unusual case of asymptomatic patient with hypothyroidism who presented with severely reduced cardiac function with elevated cardiac enzymes reflecting significant myocardial injury. Comprehensive evaluation for heart failure was suggestive only for long-standing untreated hypothyroidism. Endomyocadial biopsy demonstrated unique histological findings of mucopolysaccharide accumulation attributed to hypothyroid state. Asymptomatic hypothyroidism may cause severe reduction in cardiac function accompanied with elevated cardiac enzymes. To our knowledge, this is the first description of human myocardial biopsy revealing mucopolysaccharide accumulation attributed to hypothyroid state.

Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study.

PubMed

Danias, Peter G; Tritos, Nicholas A; Stuber, Matthias; Kissinger, Kraig V; Salton, Carol J; Manning, Warren J

2003-07-01

Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidities. In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL, p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese.

Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

PubMed

Al-Wakeel, Nadya; O h-Ici, Darach; Schmitt, Katharina R; Messroghli, Daniel R; Riesenkampff, Eugénie; Berger, Felix; Kuehne, Titus; Peters, Bjoern

2016-02-01

In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

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.

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.

Positron Emission Tomography of the Heart

DOE R&D Accomplishments Database

Schelbert, H. R.; Phelps, M. E.; Kuhl, D. E.

1979-01-01

Positron emission computed tomography (PCT) represents an important new tool for the noninvasive evaluation and, more importantly, quantification of myocardial performance. Most currently available techniques permit assessment of only one aspect of cardiac function, i.e., myocardial perfusion by gamma scintillation camera imaging with Thallium-201 or left ventricular function by echocardiography or radionuclide angiocardiography. With PCT it may become possible to study all three major segments of myocardial performance, i.e., regional blood flow, mechanical function and, most importantly, myocardial metabolism. Each of these segments can either be evaluated separately or in combination. This report briefly describes the principles and technological advantages of the imaging device, reviews currently available radioactive tracers and how they can be employed for the assessment of flow, function and metabolism; and, lastly, discusses possible applications of PCT for the study of cardiac physiology or its potential role in the diagnosis of cardiac disease.

Evaluation of cardiac function in a group of small for gestational age school-age children treated with growth hormone.

PubMed

Aurensanz Clemente, Esther; Ayerza Casas, Ariadna; Samper Villagrasa, Pilar; Ruiz Frontera, Pablo; Bueno Lozano, Gloria

2017-02-09

Small for gestational age (SGA) patients have an increased risk of developing a cardiovascular pathology, as well as a metabolic syndrome. Our objective is to evaluate the cardiac morphology and function of SGA children treated with growth hormone (GH), identifying changes that could potentially have long-term consequences. We selected 23 SGA school-age patients and 23 healthy children. We measured their weight, height, blood pressure and heart rate. Using transthoracic echocardiography, we evaluated cardiac chamber size, ascending and abdominal aortic diameter as well as the systolic and diastolic function of both ventricles. SGA children have a higher systolic and diastolic blood pressure (P<.05) without significant changes in their heart rate. They also have a thicker interventricular septum (SGA Z-score 1.57 vs. 0.89; P=.026) and a worse right ventricular systolic function, with a lower TAPSE (SGA Z-score -0.98 vs. 0.95; P=.000), as well as a lower blood flow rate in the pulmonary artery (SGA 0.85m/s vs. 0.97m/s; P=.045). No significant difference was observed in the patients' left ventricular function. SGA patients' ascending aortic diameter was greater (SGA Z-score -1.09 vs. -1.93; P=.026), whereas the systolic abdominal aortic diameter was smaller (SGA Z-score-0.89 vs. -0.19; P=.015). We found functional and morphological cardiac changes in SGA school-age patients treated with GH. It is important to follow-up this patient group in order to determine if these changes contribute to an increased cardiac morbidity in adulthood. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Gravito-inertial sensitivity of the spider - Araneus sericatus

NASA Technical Reports Server (NTRS)

Finck, A.

1982-01-01

The gravito-inertial transfer function of the orb-weaving spider was evaluated by changes in the cardiac reflex. A non-intrusive method, using a laser system recorded the cardiac pulse. Between 1.001 and 1.5 Gz the data are 'best-fit' by a log function (r-squared 0.92). The response of the neurogenic heart is seen to be a good dependent variable for invetebrate research. The arachnid lyriform organ has those qualities which complement the obtained gravity function. It is hypothesized that the cardiac pump maintains the spiders equilibrium in the gravito-inertial field.

Bridging the gap: Hybrid cardiac echo in the critically ill.

PubMed

Glaser, Jacob J; Cardarelli, Cassandra; Galvagno, Samuel; Scalea, Thomas M; Murthi, Sarah B

2016-11-01

Point-of-care ultrasound often includes cardiac ultrasound. It is commonly used to evaluate cardiac function in critically ill patients but lacks the specific quantitative anatomic assessment afforded by standard transthoracic echocardiography (TTE). We developed the Focused Rapid Echocardiographic Examination (FREE), a hybrid between a cardiac ultrasound and TTE that places an emphasis on cardiac function rather than anatomy. We hypothesized that data obtained from FREE correlate well with TTE while providing actionable information for clinical decision making. FREE examinations evaluating cardiac function (left ventricular ejection fraction), diastolic dysfunction (including early mitral Doppler flow [E] and early mitral tissue Doppler [E']), right ventricular function, cardiac output, preload (left ventricular internal dimension end diastole), stroke volume, stroke volume variation, inferior vena cava diameter, and inferior vena cava collapse were performed. Patients who underwent both a TTE and FREE on the same day were identified as the cohort, and quantitative measurements were compared. Correlation analyses were performed to assess levels of agreement. A total of 462 FREE examinations were performed, in which 69 patients had both a FREE and TTE. FREE ejection fraction was strongly correlated with TTE (r = 0.89, 95% confidence interval). Left ventricular outflow tract, left ventricular internal dimension end diastole, E, and lateral E' derived from FREE were also strongly correlated with TTE measurements (r = 0.83, r = 0.94, r = 0.77, and r = 0.88, respectively). In 82% of the patients, right ventricular function for FREE was the same as that reported for TTE; pericardial effusion was detected on both examinations in 94% of the cases. No significant valvular anatomy was missed with the FREE examination. Functionally rather than anatomically based hybrid ultrasound examinations, like the FREE, facilitate decision making for critically ill patients. The FREE's functional assessment correlates well with TTE measurements and may be of significant clinical value in critically ill patients, especially when used in remote operating environments where resources are limited. Diagnostic test, level III.

Dynamic and quantitative evaluation of degenerative mitral valve disease: a dedicated framework based on cardiac magnetic resonance imaging.

PubMed

Sturla, Francesco; Onorati, Francesco; Puppini, Giovanni; Pappalardo, Omar A; Selmi, Matteo; Votta, Emiliano; Faggian, Giuseppe; Redaelli, Alberto

2017-04-01

Accurate quantification of mitral valve (MV) morphology and dynamic behavior over the cardiac cycle is crucial to understand the mechanisms of degenerative MV dysfunction and to guide the surgical intervention. Cardiac magnetic resonance (CMR) imaging has progressively been adopted to evaluate MV pathophysiology, although a dedicated framework is required to perform a quantitative assessment of the functional MV anatomy. We investigated MV dynamic behavior in subjects with normal MV anatomy (n=10) and patients referred to surgery due to degenerative MV prolapse, classified as fibro-elastic deficiency (FED, n=9) and Barlow's disease (BD, n=10). A CMR-dedicated framework was adopted to evaluate prolapse height and volume and quantitatively assess valvular morphology and papillary muscles (PAPs) function over the cardiac cycle. Multiple comparison was used to investigate the hallmarks associated to MV degenerative prolapse and evaluate the feasibility of anatomical and functional distinction between FED and BD phenotypes. On average, annular dimensions were significantly (P<0.05) larger in BD than in FED and normal subjects while no significant differences were noticed between FED and normal. MV eccentricity progressively decreased passing from normal to FED and BD, with the latter exhibiting a rounder annulus shape. Over the cardiac cycle, we noticed significant differences for BD during systole with an abnormal annular enlargement between mid and late systole (LS) (P<0.001 vs. normal); the PAPs dynamics remained comparable in the three groups. Prolapse height and volume highlighted significant differences among normal, FED and BD valves. Our CMR-dedicated framework allows for the quantitative and dynamic evaluation of MV apparatus, with quantifiable annular alterations representing the primary hallmark of severe MV degeneration. This may aid surgeons in the evaluation of the severity of MV dysfunction and the selection of the appropriate MV treatment.

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.

Performance of Automated Software in the Assessment of Segmental Left Ventricular Function in Cardiac CT: Comparison with Cardiac Magnetic Resonance.

PubMed

Wang, Rui; Meinel, Felix G; Schoepf, U Joseph; Canstein, Christian; Spearman, James V; De Cecco, Carlo N

2015-12-01

To evaluate the accuracy, reliability and time saving potential of a novel cardiac CT (CCT)-based, automated software for the assessment of segmental left ventricular function compared to visual and manual quantitative assessment of CCT and cardiac magnetic resonance (CMR). Forty-seven patients with suspected or known coronary artery disease (CAD) were enrolled in the study. Wall thickening was calculated. Segmental LV wall motion was automatically calculated and shown as a colour-coded polar map. Processing time for each method was recorded. Mean wall thickness in both systolic and diastolic phases on polar map, CCT, and CMR was 9.2 ± 0.1 mm and 14.9 ± 0.2 mm, 8.9 ± 0.1 mm and 14.5 ± 0.1 mm, 8.3 ± 0.1 mm and 13.6 ± 0.1 mm, respectively. Mean wall thickening was 68.4 ± 1.5 %, 64.8 ± 1.4 % and 67.1 ± 1.4 %, respectively. Agreement for the assessment of LV wall motion between CCT, CMR and polar maps was good. Bland-Altman plots and ICC indicated good agreement between CCT, CMR and automated polar maps of the diastolic and systolic segmental wall thickness and thickening. The processing time using polar map was significantly decreased compared with CCT and CMR. Automated evaluation of segmental LV function with polar maps provides similar measurements to manual CCT and CMR evaluation, albeit with substantially reduced analysis time. • Cardiac computed tomography (CCT) can accurately assess segmental left ventricular wall function. • A novel automated software permits accurate and fast evaluation of wall function. • The software may improve the clinical implementation of segmental functional analysis.

Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

ERIC Educational Resources Information Center

Junqueira, Luiz Fernando, Jr.

2008-01-01

In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

Relationship of cardiac structure and function to cardiorespiratory fitness and lean body mass in adolescents and young adults with Type 2 Diabetes

USDA-ARS?s Scientific Manuscript database

To investigate the relationships of cardiac structure and function with body composition and cardiorespiratory fitness (CRF) among adolescents with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study Group. Cross-sectional evaluation of 233 participant...

The six-minute walk test in patients with AL amyloidosis: a single centre case series.

PubMed

Pulido, Vina; Doros, Gheorghe; Berk, John L; Sanchorawala, Vaishali

2017-05-01

The six-minute walk test (6MWT) has been widely used as an objective evaluation of functional exercise capacity and response to medical intervention in cardiopulmonary diseases. However, little is known about the 6MWT in evaluating patients with AL amyloidosis. We performed a retrospective study of 120 adults with systemic AL amyloidosis (60 with cardiac involvement and 60 without cardiac involvement) who had their initial evaluation at the Amyloidosis Center between 2013 and 2015 and had undergone 6MWT as a measure of functional exercise capacity. Forty-seven patients with cardiac involvement and 41 patients without cardiac involvement were included in the final analysis. The six-minute walk distances (6MWD) were 368 ± 105 m and 420 ± 116 m (mean ± SD), respectively (P = 0·03). Among AL amyloidosis patients with cardiac involvement, the 6MWD was associated with New York Heart Association class (P < 0·001), B-type natriuretic peptide (P = 0·003) and overall survival (hazard ratio 0·381, 95% confidence interval 0·215-0·676, P = 0·001). In conclusion, the 6MWT is a valuable tool in assessing functional exercise capacity in patients with AL amyloidosis. © 2017 John Wiley & Sons Ltd.

Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

PubMed

Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

2016-11-25

In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

Evaluation of child and parent outcomes after a pediatric cardiac camp experience.

PubMed

Bultas, Margaret W; Budhathoki, Chakra; Balakas, Karen

2013-10-01

This study evaluated the effects of a cardiac camp experience on children with heart disease and their parents. A repeated measures design was used with 49 parent-child dyads. Repeated measures evaluated the effects of camp on anxiety, attitude toward illness, and psychosocial functioning of the children. Parental anxiety was also evaluated. Results demonstrated decreases in parent anxiety, decreases in child trait anxiety, and positive psychosocial outcomes in the areas of self-esteem, social, physical, and emotional functioning. Findings can be used to support decisions for those contemplating a camping experience for the child with heart disease. © 2013, Wiley Periodicals, Inc.

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

Focused cardiac ultrasound using a pocket-size device in the emergency room.

PubMed

Mancuso, Frederico José Neves; Siqueira, Vicente Nicoliello; Moisés, Valdir Ambrósio; Gois, Aécio Flavio Teixeira; Paola, Angelo Amato Vincenzo de; Carvalho, Antonio Carlos Camargo; Campos, Orlando

2014-12-01

Cardiovascular urgencies are frequent reasons for seeking medical care. Prompt and accurate medical diagnosis is critical to reduce the morbidity and mortality of these conditions. To evaluate the use of a pocket-size echocardiography in addition to clinical history and physical exam in a tertiary medical emergency care. One hundred adult patients without known cardiac or lung diseases who sought emergency care with cardiac complaints were included. Patients with ischemic changes in the electrocardiography or fever were excluded. A focused echocardiography with GE Vscan equipment was performed after the initial evaluation in the emergency room. Cardiac chambers dimensions, left and right ventricular systolic function, intracardiac flows with color, pericardium, and aorta were evaluated. The mean age was 61 ± 17 years old. The patient complaint was chest pain in 51 patients, dyspnea in 32 patients, arrhythmia to evaluate the left ventricular function in ten patients, hypotension/dizziness in five patients and edema in one patient. In 28 patients, the focused echocardiography allowed to confirm the initial diagnosis: 19 patients with heart failure, five with acute coronary syndrome, two with pulmonary embolism and two patients with cardiac tamponade. In 17 patients, the echocardiography changed the diagnosis: ten with suspicious of heart failure, two with pulmonary embolism suspicious, two with hypotension without cause, one suspicious of acute coronary syndrome, one of cardiac tamponade and one of aortic dissection. The focused echocardiography with pocket-size equipment in the emergency care may allow a prompt diagnosis and, consequently, an earlier initiation of the therapy.

[Preliminary study of rabbit experiment modality for evaluating cardiac fatigue].

PubMed

Yan, Xiaobo; Luo, Linmei; Liu, Leichu; Xiao, Shouzhong; Deng, Suyuan; Xiang, Lingli; Zhang, Cong

2013-04-01

This paper presents a preliminary study of rabbit experiment modality incorporating a new indicator for evaluating cardiac function changes, providing a basis for subsequent study of cardiac fatigue. Using only biochemical indicators, such as troponins, is difficult to make a distinction between exercise-induced cardiac fatigue (EICF) and exercise-induced cardiac damage (EICD). Therefore, some new indicators are needed to evaluate cardiac fatigue synthetically. In our study, we used New Zealand white rabbits to conduct a multi-step swimming experiments with load. We made the rabbits reach an exhaustive state to evaluate whether the amplitude ratio of the first to second heart sound (S1/S2) and heart rate (HR) during the exhaustive exercise would be decreased and whether they would be able to recover after the exhaustive exercise for 24 hours. During the first phase of swimming, S1/S2 and HR were increased, and then decreased at exhaustive state. They were recovered after the exhaustive exercise for 24 hours. Overloading led to deaths of three rabbis, and new phenomena from overloading and related to this kind of death were observed. The experiments proved that Multi-steps swimming experiments with loads by using New Zealand white rabbit is useful for studying cardiac fatigue and premonition of sudden cardiac death.

Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure.

PubMed

Manchini, Martha T; Antônio, Ednei L; Silva Junior, José Antônio; de Carvalho, Paulo de Tarso C; Albertini, Regiane; Pereira, Fernando C; Feliciano, Regiane; Montemor, Jairo; Vieira, Stella S; Grandinetti, Vanessa; Yoshizaki, Amanda; Chaves, Marcio; da Silva, Móises P; de Lima, Rafael do Nascimento; Bocalini, Danilo S; de Melo, Bruno L; Tucci, Paulo J F; Serra, Andrey J

2017-01-01

Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and -dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt 1 /VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.

High prevalence of cardiac hypertophy without detectable signs of fibrosis in patients with untreated active acromegaly: an in vivo study using magnetic resonance imaging.

PubMed

Bogazzi, Fausto; Lombardi, Massimo; Strata, Elisabetta; Aquaro, Giovanni; Di Bello, Vitantonio; Cosci, Chiara; Sardella, Chiara; Talini, Enrica; Martino, Enio

2008-03-01

Left ventricular (LV) hypertrophy and myocardial fibrosis are considered the main pathological features of acromegalic cardiomyopathy. The aim of the study was to evaluate the proportion of LV hypertrophy and the presence of fibrosis in acromegalic cardiomyopathy in vivo using cardiac magnetic resonance (CMR). Fourteen consecutive patients (eight women, mean age 46 +/- 10 years) with untreated active acromegaly were submitted to two-dimensional (2D) colour Doppler and integrated backscatter (IBS) echocardiography and CMR. LV volume, mass and wall thickness and myocardial tissue characterization (IBS and CMR). On echocardiography: mean LV mass (LVM) and LVM index (LVMi) were 209 +/- 48 g and 110 +/- 24 g/m(2), respectively; hypertrophy was revealed in five patients (36%); abnormal diastolic function [evaluated by isovolumic relaxation time (IVRT) or early (E) to late or atrial (A) peak velocities (E/A ratio)] was found in four patients (29%). Systolic function evaluated by measuring LV ejection fraction (LVEF) was normal (mean 72 +/- 12%) in all patients. Six patients (43%) had increased IBS (mean 57.4 +/- 6.2%). On CMR: mean LVM and LVMi were 151 +/- 17 g and 76 +/- 9 g/m(2), respectively; 10 patients (72%) had LV hypertrophy. Contrastographic delayed hyperenhancement was absent in all patients; on the contrary, mild enhancement was revealed in one patient. Systolic function was normal in all patients (LVEF 67 +/- 11%). LVMi was not related to serum IGF-1 concentrations or the estimated duration of disease. CMR is considered to be the gold standard for evaluating cardiac hypertrophy, fibrosis and systolic function. Using CMR, 72% patients with untreated active acromegaly had LV hypertrophy, which was only detected in 36% patients by echocardiography. However, cardiac fibrosis was absent in all patients irrespective of the estimated duration of disease. Although a very small increase in collagen content (as suggested by increased cardiac reflectivity at IBS), not detectable by CMR, could not be ruled out, it is unlikely that it would significantly affect cardiac function.

Cardiac and Metabolic Variables in Obese Dogs.

PubMed

Tropf, M; Nelson, O L; Lee, P M; Weng, H Y

2017-07-01

The etiology of obesity-related cardiac dysfunction (ORCD) is linked to metabolic syndrome in people. Studies have indicated that obese dogs have components of metabolic syndrome, warranting evaluation for ORCD in obese dogs. To evaluate cardiac structure and function and metabolic variables in obese dogs compared to ideal weight dogs. Forty-six healthy, small-breed (<25 pounds), obese dogs (n = 29) compared to ideal weight dogs (n = 17). A cross-sectional study of cardiac structure and function by standard and strain echocardiographic measurements and quantification of serum metabolic variables (insulin:glucose ratios, lipid analysis, adiponectin, inflammatory markers). Compared to the ideal weight controls, obese dogs had cardiac changes characterized by an increased interventricular septal width in diastole to left ventricular internal dimension in diastole ratio, decreased ratios of peak early to peak late left ventricular inflow velocities, and ratios of peak early to peak late mitral annular tissue velocities, and increased fractional shortening and ejection fraction percentages. The left ventricular posterior wall width in diastole to left ventricular internal dimension in diastole ratios were not significantly different between groups. Systolic blood pressure was not significantly different between groups. Obese dogs had metabolic derangements characterized by increased insulin:glucose ratios, dyslipidemias with increased cholesterol, triglyceride, and high-density lipoprotein concentrations, decreased adiponectin concentrations, and increased concentrations of interleukin 8 and keratinocyte-derived chemokine-like inflammatory cytokines. Compared to ideal weight controls, obese dogs have alterations in cardiac structure and function as well as insulin resistance, dyslipidemia, hypoadiponectinemia, and increased concentrations of inflammatory markers. These findings warrant additional studies to investigate inflammation, dyslipidemia, and possibly systemic hypertension as potential contributing factors for altered cardiac function. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine-16 without affecting calcium handling.

PubMed

Lima-Leopoldo, Ana Paula; Leopoldo, André S; da Silva, Danielle C T; do Nascimento, André F; de Campos, Dijon H S; Luvizotto, Renata A M; de Deus, Adriana F; Freire, Paula P; Medeiros, Alessandra; Okoshi, Katashi; Cicogna, Antonio C

2014-09-15

Few studies have evaluated the relationship between the duration of obesity, cardiac function, and the proteins involved in myocardial calcium (Ca(2+)) handling. We hypothesized that long-term obesity promotes cardiac dysfunction due to a reduction of expression and/or phosphorylation of myocardial Ca(2+)-handling proteins. Thirty-day-old male Wistar rats were distributed into two groups (n = 10 each): control (C; standard diet) and obese (Ob; high-fat diet) for 30 wk. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle. Cardiac protein expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), calsequestrin, L-type Ca(2+) channel, and phospholamban (PLB), as well as PLB serine-16 phosphorylation (pPLB Ser(16)) and PLB threonine-17 phosphorylation (pPLB Thr(17)) were determined by Western blot. The adiposity index was higher (82%) in Ob rats than in C rats. Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C. The Ob muscles developed similar baseline data and myocardial responsiveness to increased extracellular Ca(2+). Obesity caused a reduction in cardiac pPLB Ser(16) and the pPLB Ser(16)/PLB ratio in Ob rats. Long-term obesity promotes alterations in diastolic function, most likely due to the reduction of pPLB Ser(16), but does not impair the myocardial Ca(2+) entry and recapture to SR. Copyright © 2014 the American Physiological Society.

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

Inhalation of Photochemically Altered Urban Mixtures Depresses Cardiac Function in Mice

EPA Science Inventory

Rationale: Epidemiological studies have indicated an association between urban air pollution exposure and cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of inhaled photochemical products in urban mixtures in a murine model. ...

The treatment with pyridostigmine improves the cardiocirculatory function in rats with chronic heart failure.

PubMed

Sabino, João Paulo J; da Silva, Carlos Alberto Aguiar; de Melo, Rubens Fernando; Fazan, Rubens; Salgado, Helio C

2013-01-01

Sympathetic hyperactivity and its outcome in heart failure have been thoroughly investigated to determine the focus of pharmacologic approaches targeting the sympathetic nervous system in the treatment of this pathophysiological condition. On the other hand, therapeutic approaches aiming to protect the reduced cardiac parasympathetic function have not received much attention. The present study evaluated rats with chronic heart failure (six to seven weeks after coronary artery ligation) and the effects of an increased parasympathetic function by pyridostigmine (an acetylcholinesterase inhibitor) on the following aspects: arterial pressure (AP), heart rate (HR), baroreceptor and Bezold-Jarisch reflex, pulse interval (PI) and AP variability, cardiac sympathetic and parasympathetic tonus, intrinsic heart rate (i-HR) and cardiac function. Conscious rats with heart failure exhibited no change in HR, Bezold-Jarisch reflex, PI variability and cardiac sympathetic tonus. On the other hand, these animals presented hypotension and reduced baroreflex sensitivity, power in the low frequency (LF) band of the systolic AP spectrum, cardiac parasympathetic tonus and i-HR, while anesthetized rats exhibited reduced cardiac performance. Pyridostigmine prevented the attenuation of all the parameters examined, except basal AP and cardiac performance. In conclusion, the blockade of acetylcholinesterase with pyridostigmine was revealed to be an important pharmacological approach, which could be used to increase parasympathetic function and to improve a number of cardiocirculatory parameters in rats with heart failure. Copyright © 2012 Elsevier B.V. All rights reserved.

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

The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

PubMed

Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

2014-04-01

The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

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.

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.

Inhalation of Simulated Smog Atmospheres Affects Cardiac Function in Mice

EPA Science Inventory

The health effects of individual criteria air pollutants have been well investigated. However, little is known about the health effects of air pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the cardiac eff...

Low molecular weight fucoidan alleviates cardiac dysfunction in diabetic Goto-Kakizaki rats by reducing oxidative stress and cardiomyocyte apoptosis.

PubMed

Yu, Xinfeng; Zhang, Quanbin; Cui, Wentong; Zeng, Zheng; Yang, Wenzhe; Zhang, Chao; Zhao, Hongwei; Gao, Weidong; Wang, Xiaomin; Luo, Dali

2014-01-01

Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte apoptosis. Oxidative stress is suggested to be the major contributor to the development of DCM. This study was intended to evaluate the protective effect of low molecular weight fucoidan (LMWF) against cardiac dysfunction in diabetic rats. Type 2 diabetic goto-kakizaki rats were untreated or treated with LMWF (50 and 100 mg/kg/day) for three months. The establishment of DCM model and the effects of LMWF on cardiac function were evaluated by echocardiography and isolated heart perfusion. Ventricle staining with H-E or Sirius Red was performed to investigate the structural changes in myocardium. Functional evaluation demonstrated that LMWF has a beneficial effect on DCM by enhancing myocardial contractility and mitigating cardiac fibrosis. Additionally, LMWF exerted significant inhibitory effects on the reactive oxygen species production and myocyte apoptosis in diabetic hearts. The depressed activity of superoxide dismutase in diabetic heart was also improved by intervention with LMWF. Moreover, LMWF robustly inhibited the enhanced expression of protein kinase C β, an important contributor to oxidative stress, in diabetic heart and high glucose-treated cardiomyocytes. In conclusion, LMWF possesses a protective effect against DCM through ameliorations of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis in diabetes.

Imaging cardiac extracellular matrices: a blueprint for regeneration

PubMed Central

Jung, Jangwook P.; Squirrell, Jayne M.; Lyons, Gary E.; Eliceiri, Kevin W.; Ogle, Brenda M.

2013-01-01

Once damaged, cardiac tissue does not readily repair and is therefore a primary target of regenerative therapies. One regenerative approach is the development of scaffolds that functionally mimic the cardiac extracellular matrix (ECM) to deliver stem cells or cardiac precursor populations to the heart. Technological advances in micro/nanotechnology, stem cell biology, biomaterials and tissue decellularization have propelled this promising approach forward. Surprisingly, technological advances in optical imaging methods have not been fully utilized in the field of cardiac regeneration. Here, we describe and provide examples to demonstrate how advanced imaging techniques could revolutionize how ECM-mimicking cardiac tissues are informed and evaluated. PMID:22209562

An ontology-based annotation of cardiac implantable electronic devices to detect therapy changes in a national registry.

PubMed

Rosier, Arnaud; Mabo, Philippe; Chauvin, Michel; Burgun, Anita

2015-05-01

The patient population benefitting from cardiac implantable electronic devices (CIEDs) is increasing. This study introduces a device annotation method that supports the consistent description of the functional attributes of cardiac devices and evaluates how this method can detect device changes from a CIED registry. We designed the Cardiac Device Ontology, an ontology of CIEDs and device functions. We annotated 146 cardiac devices with this ontology and used it to detect therapy changes with respect to atrioventricular pacing, cardiac resynchronization therapy, and defibrillation capability in a French national registry of patients with implants (STIDEFIX). We then analyzed a set of 6905 device replacements from the STIDEFIX registry. Ontology-based identification of therapy changes (upgraded, downgraded, or similar) was accurate (6905 cases) and performed better than straightforward analysis of the registry codes (F-measure 1.00 versus 0.75 to 0.97). This study demonstrates the feasibility and effectiveness of ontology-based functional annotation of devices in the cardiac domain. Such annotation allowed a better description and in-depth analysis of STIDEFIX. This method was useful for the automatic detection of therapy changes and may be reused for analyzing data from other device registries.

[Cardiac surgery in octogenarian patients: evaluation of predictive factors of mortality, long-term outcome and quality of life].

PubMed

Viana-Tejedor, Ana; Domínguez, Francisco J; Moreno Yangüela, Mar; Moreno, Raúl; López de Sá, Esteban; Mesa, José M; López-Sendón, José

2008-10-04

Increasing life expectancy in Western countries in the last decades has resulted in a significant gradual increasing number of octogenarians referred for cardiac surgery. There is a need for a critical evaluation of the long-term surgical outcome and quality of life in the elderly. The aim of this study is to identify risk factors of mortality in octogenarians undergoing cardiac surgery and to assess the long term survival and quality of life. Data were reviewed on 150 patients aged over 80 years--mean age (standard deviation): 82.7 (2.5) years--who underwent cardiac surgery at our institution in the last 26 years. We analyzed clinical and epidemiological variables included in the European System for Cardiac Operative Risk Evaluation (euroSCORE), in-hospital morbidity and mortality, long term survival and quality of life after cardiac surgery. The 30-day mortality rate was 30.1%, with a mean hospital stay of 16.5 days (13-27). Emergent procedure, reparation of postinfarction ventricular ruptures, New York Heart Association functional class IV, chronic renal failure and previous myocardial infarction were independent predictors of in-hospital mortality. Mean follow up was 72.2 (9.9) months with survival rates of 87.3% and 57% at 1 and 5 years, respectively. Late postoperative quality of life in our 53 long-term survivors was significantly better than prior to surgery. New York Heart Association functional class improved from 2.52 to 1.48. Most survivors (97.7%) were satisfied with present quality of life Cardiac surgery in octogenarians is associated with increased in-hospital mortality rate and longer hospital stay. Our findings support that cardiac surgery can be performed in a selected elderly population with good long-term survival and quality of life.

Focused Cardiac Ultrasound Using a Pocket-Size Device in the Emergency Room

PubMed Central

Mancuso, Frederico José Neves; Siqueira, Vicente Nicoliello; Moisés, Valdir Ambrósio; Gois, Aécio Flavio Teixeira; de Paola, Angelo Amato Vincenzo; Carvalho, Antonio Carlos Camargo; Campos, Orlando

2014-01-01

Background Cardiovascular urgencies are frequent reasons for seeking medical care. Prompt and accurate medical diagnosis is critical to reduce the morbidity and mortality of these conditions. Objective To evaluate the use of a pocket-size echocardiography in addition to clinical history and physical exam in a tertiary medical emergency care. Methods One hundred adult patients without known cardiac or lung diseases who sought emergency care with cardiac complaints were included. Patients with ischemic changes in the electrocardiography or fever were excluded. A focused echocardiography with GE Vscan equipment was performed after the initial evaluation in the emergency room. Cardiac chambers dimensions, left and right ventricular systolic function, intracardiac flows with color, pericardium, and aorta were evaluated. Results The mean age was 61 ± 17 years old. The patient complaint was chest pain in 51 patients, dyspnea in 32 patients, arrhythmia to evaluate the left ventricular function in ten patients, hypotension/dizziness in five patients and edema in one patient. In 28 patients, the focused echocardiography allowed to confirm the initial diagnosis: 19 patients with heart failure, five with acute coronary syndrome, two with pulmonary embolism and two patients with cardiac tamponade. In 17 patients, the echocardiography changed the diagnosis: ten with suspicious of heart failure, two with pulmonary embolism suspicious, two with hypotension without cause, one suspicious of acute coronary syndrome, one of cardiac tamponade and one of aortic dissection. Conclusion The focused echocardiography with pocket-size equipment in the emergency care may allow a prompt diagnosis and, consequently, an earlier initiation of the therapy. PMID:25590933

Losartan Decreases Cardiac Muscle Fibrosis and Improves Cardiac Function in Dystrophin-Deficient Mdx Mice

PubMed Central

Spurney, Christopher F.; Sali, Arpana; Guerron, Alfredo D.; Iantorno, Micaela; Yu, Qing; Gordish-Dressman, Heather; Rayavarapu, Sree; van der Meulen, Jack; Hoffman, Eric P.; Nagaraju, Kanneboyina

2014-01-01

Recent studies showed that chronic administration of losartan, an angiotensin II type I receptor antagonist, improved skeletal muscle function in dystrophin-deficient mdx mice. In this study, C57BL/10ScSn-Dmdmdx/J female mice were either untreated or treated with losartan (n = 15) in the drinking water at a dose of 600 mg/L over a 6-month period. Cardiac function was assessed via in vivo high frequency echocardiography and skeletal muscle function was assessed using grip strength testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed using picrosirius red staining and Image J analysis. Gene expression was evaluated using real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was significantly decreased in untreated (26.9% ± 3.5%) mice compared to losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was significantly reduced in losartan-treated mice (56 ± 6 vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was significantly reduced in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscles compared to untreated mdx mice. There were no significant differences in skeletal muscle function between treated and untreated groups. Chronic treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice. PMID:21304057

The use of the virtual reality as intervention tool in the postoperative of cardiac surgery.

PubMed

Cacau, Lucas de Assis Pereira; Oliveira, Géssica Uruga; Maynard, Luana Godinho; Araújo Filho, Amaro Afrânio de; Silva, Walderi Monteiro da; Cerqueria Neto, Manoel Luiz; Antoniolli, Angelo Roberto; Santana-Filho, Valter J

2013-06-01

Cardiac surgery has been the intervention of choice in many cases of cardiovascular diseases. Susceptibility to postoperative complications, cardiac rehabilitation is indicated. Therapeutic resources, such as virtual reality has been helping the rehabilitational process. The aim of the study was to evaluate the use of virtual reality in the functional rehabilitation of patients in the postoperative period. Patients were randomized into two groups, Virtual Reality (VRG, n = 30) and Control (CG, n = 30). The response to treatment was assessed through the functional independence measure (FIM), by the 6-minute walk test (6MWT) and the Nottingham Health Profile (NHP). Evaluations were performed preoperatively and postoperatively. On the first day after surgery, patients in both groups showed decreased functional performance. However, the VRG showed lower reduction (45.712.3) when compared to CG (35.0612.09, P<0.05) in first postoperative day, and no significant difference in performance on discharge day (P>0.05). In evaluating the NHP field, we observed a significant decrease in pain score at third assessment (P<0.05). These patients also had a higher energy level in the first evaluation (P<0.05). There were no differences with statistical significance for emotional reactions, physical ability, and social interaction. The length of stay was significantly shorter in patients of VRG (9.410.5 days vs. 12.2 1 0.9 days, P<0.05), which also had a higher 6MWD (319.9119.3 meters vs. 263.5115.4 meters, P<0.02). Adjunctive treatment with virtual reality demonstrated benefits, with better functional performance in patients undergoing cardiac surgery.

Characterization of Glutamatergic Neurons in the Rat Atrial Intrinsic Cardiac Ganglia that Project to the Cardiac Ventricular Wall

PubMed Central

Wang, Ting; Miller, Kenneth E.

2016-01-01

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system. PMID:27167082

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis

PubMed Central

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis. PMID:29161313

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

PubMed

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You; Chu, Chun-Lin

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Effect of hydration status on atrial and ventricular volumes and function in healthy adult volunteers.

PubMed

Schantz, Daryl I; Dragulescu, Andreea; Memauri, Brett; Grotenhuis, Heynric B; Seed, Mike; Grosse-Wortmann, Lars

2016-10-01

Assessment of cardiac chamber volumes is a fundamental part of cardiac magnetic resonance (CMR) imaging. While the effects of inter- and intraobserver variability have been studied and have a recognized effect on the comparability of serial cardiac MR imaging studies, the effect of differences in hydration status has not been evaluated. To evaluate the effects of volume administration on cardiac chamber volumes. Thirteen healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber volumes after an overnight fast. They were then given two saline boluses of 10 ml/kg of body weight and the cardiac MR was repeated immediately after each bolus. From the baseline scan to the final scan there was a significant increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes increased 8.0%, from 61.1 to 66.0 ml/m2 (P<0.001), and left atrial volumes increased 10.0%, from 50.0 to 55.0 ml/m2 (P<0.001). Right ventricular volumes increased 6.0%, from 91.1 to 96.5 ml/m2 (P<0.001), and left ventricular volumes increased 3.2%, from 87.0 to 89.8 ml/m2 (P<0.001). Hydration status has a significant effect on the end-diastolic volumes of all cardiac chambers assessed by cardiac MR. Thus, hydration represents a "variable" that should be taken into account when assessing cardiac chamber volumes, especially when performing serial imaging studies in a patient.

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

PubMed Central

Herradón, Esperanza; González, Cristina; Uranga, José A.; Abalo, Raquel; Martín, Ma I.; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations. PMID:28533750

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments.

PubMed

Herradón, Esperanza; González, Cristina; Uranga, José A; Abalo, Raquel; Martín, Ma I; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

Dynamic and quantitative evaluation of degenerative mitral valve disease: a dedicated framework based on cardiac magnetic resonance imaging

PubMed Central

Onorati, Francesco; Puppini, Giovanni; Pappalardo, Omar A.; Selmi, Matteo; Votta, Emiliano; Faggian, Giuseppe; Redaelli, Alberto

2017-01-01

Background Accurate quantification of mitral valve (MV) morphology and dynamic behavior over the cardiac cycle is crucial to understand the mechanisms of degenerative MV dysfunction and to guide the surgical intervention. Cardiac magnetic resonance (CMR) imaging has progressively been adopted to evaluate MV pathophysiology, although a dedicated framework is required to perform a quantitative assessment of the functional MV anatomy. Methods We investigated MV dynamic behavior in subjects with normal MV anatomy (n=10) and patients referred to surgery due to degenerative MV prolapse, classified as fibro-elastic deficiency (FED, n=9) and Barlow’s disease (BD, n=10). A CMR-dedicated framework was adopted to evaluate prolapse height and volume and quantitatively assess valvular morphology and papillary muscles (PAPs) function over the cardiac cycle. Multiple comparison was used to investigate the hallmarks associated to MV degenerative prolapse and evaluate the feasibility of anatomical and functional distinction between FED and BD phenotypes. Results On average, annular dimensions were significantly (P<0.05) larger in BD than in FED and normal subjects while no significant differences were noticed between FED and normal. MV eccentricity progressively decreased passing from normal to FED and BD, with the latter exhibiting a rounder annulus shape. Over the cardiac cycle, we noticed significant differences for BD during systole with an abnormal annular enlargement between mid and late systole (LS) (P<0.001 vs. normal); the PAPs dynamics remained comparable in the three groups. Prolapse height and volume highlighted significant differences among normal, FED and BD valves. Conclusions Our CMR-dedicated framework allows for the quantitative and dynamic evaluation of MV apparatus, with quantifiable annular alterations representing the primary hallmark of severe MV degeneration. This may aid surgeons in the evaluation of the severity of MV dysfunction and the selection of the appropriate MV treatment. PMID:28540065

Advances in cardiac CT contrast injection and acquisition protocols.

PubMed

Scholtz, Jan-Erik; Ghoshhajra, Brian

2017-10-01

Cardiac computed tomography (CT) imaging has become an important part of modern cardiovascular care. Coronary CT angiography (CTA) is the first choice imaging modality for non-invasive visualization of coronary artery stenosis. In addition, cardiac CT does not only provide anatomical evaluation, but also functional and valvular assessment, and myocardial perfusion evaluation. In this article we outline the factors which influence contrast enhancement, give an overview of current contrast injection and acquisition protocols, with focus on current emerging topics such as pre-transcatheter aortic valve replacement (TAVR) planning, cardiac CT for congenital heart disease (CHD) patients, and myocardial CT perfusion (CTP). Further, we point out areas where we see potential for future improvements in cardiac CT imaging based on a closer interaction between CT scanner settings and contrast injection protocols to tailor injections to patient- and exam-specific factors.

Advances in cardiac CT contrast injection and acquisition protocols

PubMed Central

Scholtz, Jan-Erik

2017-01-01

Cardiac computed tomography (CT) imaging has become an important part of modern cardiovascular care. Coronary CT angiography (CTA) is the first choice imaging modality for non-invasive visualization of coronary artery stenosis. In addition, cardiac CT does not only provide anatomical evaluation, but also functional and valvular assessment, and myocardial perfusion evaluation. In this article we outline the factors which influence contrast enhancement, give an overview of current contrast injection and acquisition protocols, with focus on current emerging topics such as pre-transcatheter aortic valve replacement (TAVR) planning, cardiac CT for congenital heart disease (CHD) patients, and myocardial CT perfusion (CTP). Further, we point out areas where we see potential for future improvements in cardiac CT imaging based on a closer interaction between CT scanner settings and contrast injection protocols to tailor injections to patient- and exam-specific factors. PMID:29255688

[Donation protocol following controlled cardiac death (Maastricht type III donation). First experience].

PubMed

Rubio-Muñoz, J J; Pérez-Redondo, M; Alcántara-Carmona, S; Lipperheide-Vallhonrat, I; Fernández-Simón, I; Valdivia-de la Fuente, M; Villanueva-Fernández, H; Balandín-Moreno, B; Ortega-López, A; Romera-Ortega, M A; Galdos-Anuncibay, P

2014-03-01

To present our experience with the implementation of a donation protocol following controlled cardiac death (Maastricht type III donation). A retrospective descriptive and observational study was made. Intensive Care Unit of a third-level university hospital. Eight patients in an irreversible state, in which withdrawal of all life support had been agreed, were evaluated as potential donors. Application of the adopted protocol. Clinical data of donors, evaluation of a donation protocol following cardiac death, warm ischemia times, and short-term outcome of the recipients. Eight patients were evaluated. In one case donation was not possible because no cardiac arrest developed in the 120 minutes after extubation. The 7 remaining patients were effective kidney donors. Warm ischemia times were less than 23 minutes in all cases. Although 7 of the 14 recipients suffered delayed graft function, all of them achieved good renal function. Donation after cardiac death in patients in an overwhelming and irreversible state represents a potential source of donors not previously considered in this country. The prior development of a consensus-based protocol can help increase the number of organs in combination with those obtained after brain death. In our experience, the results of kidney transplants obtained from donors after cardiac death are good, and the success of these types of protocols could be extended to other organs such as the liver and lungs. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Technical aspects of cardiac PET/MRI.

PubMed

Masuda, Atsuro; Nemoto, Ayaka; Takeishi, Yasuchika

2018-06-01

PET/MRI is a novel modality that enables to combine PET and MR images, and has significant potential to evaluate various cardiac diseases through the combination of PET molecular imaging and MRI functional imaging. Precise management of technical issues, however, is necessary for cardiac PET/MRI. This article describes several technical points, including patient preparation, MR attenuation correction, parallel acquisition of PET with MRI, clinical aspects, and image quality control.

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.

Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

PubMed

Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

2016-12-01

Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

[Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac remodeling and cardiac dysfunction following myocardial infarction in mice].

PubMed

Zhang, Jian; Jin, Zhe; Li, Longhu; Gang, Li; Yu, Qin; Wang, Meilan; Song, Ailin; Hong, Bingzhe

2014-04-01

To observe the impact of PDE5shRNA on cardiac remodeling and heart function following myocardial infarction in mice. Myocardial infarction (MI) was induced in mice by left coronary artery ligation. Mice were randomly assigned to sham group (n = 6), PDE5shRNA group (n = 12), common adenovirus group (n = 15) and DMEM group (n = 8). Four weeks post-MI, the survival rate was evaluated. Cardiac function was examined by echocardiography. HE staining and Masson staining were used to evaluate the myocardial infarction size and fibrosis. The number of blood vessels was evaluated by immunohistochemistry, PDE5 protein expression in the left ventricular was detected using Western blot, level of cGMP or PKG activity in the left ventricle was evaluated with ELISA. Four weeks post-MI, all mice survived in the sham group, 3(37%) mice died in the DMEM group, 1 (8%) died in the PDE5shRNA group and 5 died in the common adenovirus group (33%). Infarct size was significantly reduced in PDE5shRNA group compared with the common adenovirus group and DMEM group [(25.4 ± 2.9)% vs. (42.0 ± 3.2)% and (43.4 ± 2.6) %, P < 0.05]. Cardiac function was significantly improved in PDE5shRNA group compared to common adenovirus group and DMEM group[LVFS: (21.1 ± 3.7)% vs. (14.2 ± 2.9)% and (14.22 ± 2.91)%, all P < 0.05; LVEF: (48.2 ± 7.1)% vs. (34.6 ± 6.2)% and (38.1 ± 2.8)%, all P < 0.05; LVESD: (3.87 ± 0.45) mm vs.(4.91 ± 0.62) mm and (4.63 ± 0.37) mm, all P < 0.05]. The blood vessel density was also higher in PDE5shRNA group compared with common adenovirus group (infarct area:14.3 ± 2.0 vs. 6.6 ± 1.2, P < 0.05; periinfarct area: 23.6 ± 2.1 vs. 13.7 ± 2.4, P < 0.05). Compared with common adenovirus group, level of PDE5 was significantly downregulated and level of cGMP or PKG was significantly upregulated in PDE5shRNA group (all P < 0.05). Present study suggests PDE5shRNA improves cardiac function and attenuates cardiac remodeling through reducing infarction size and cardiac fibrosis and these beneficial effects are possibly mediated by activating cGMP/PKG signaling pathway.

The left heart can only be as good as the right heart: determinants of function and dysfunction of the right ventricle.

PubMed

Magder, Sheldon

2007-12-01

Discussions of cardiac physiology and pathophysiology most often emphasise the function of the left heart. However, right heart dysfunction plays an important role in critically ill patients and is often not recognised. This is probably because the role of the right ventricle is for generating flow more than pressure, and flow is not easy to evaluate. Of importance, when right ventricular function limits cardiac output, assessing left ventricular function gives little indication of overall cardiac performance. It has recently become evident that the right ventricle also has different genetic origins and characteristics from the left ventricle. The right and left ventricles interact through series effects, diastolic interactions and systolic interactions. The mechanisms of these, and their physiological and pathological significance are discussed.

Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

PubMed Central

Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

2014-01-01

Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction. PMID:24429673

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.

Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats.

PubMed

Lu, Yi; Wu, Qing; Liu, Long-Zhu; Yu, Xiao-Jiang; Liu, Jin-Jun; Li, Man-Xiang; Zang, Wei-Jin

2018-04-01

Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Early Evaluation of the Fetal Heart.

PubMed

Hernandez-Andrade, Edgar; Patwardhan, Manasi; Cruz-Lemini, Mónica; Luewan, Suchaya

2017-01-01

Evaluation of the fetal heart at 11-13 + 6 weeks of gestation is indicated for women with a family history of congenital heart defects (CHD), a previous child with CDH, or an ultrasound finding associated with cardiac anomalies. The accuracy for early detection of CHD is highly related to the experience of the operator. The 4-chamber view and outflow tracts are the most important planes for identification of an abnormal heart, and can be obtained in the majority of fetuses from 11 weeks of gestation onward. Transvaginal ultrasound is the preferred route for fetal cardiac examination prior to 12 weeks of gestation, whereas, after 12 weeks, the fetal heart can be reliably evaluated by transabdominal ultrasound. Cardiac defects, such as ventricular septal defects, tetralogy of Fallot, Ebstein's anomaly, or cardiac tumors, are unlikely to be identified at ≤14 weeks of gestation. Additional ultrasound techniques such as spatiotemporal image correlation and the evaluation of volumes by a fetal-heart expert can improve the detection of congenital heart disease. The evaluation of the fetal cardiac function at 11-13 + 6 weeks of gestation can be useful for early identification of fetuses at risk of anemia due to hemoglobinopathies, such as hemoglobin Bart's disease. © 2017 S. Karger AG, Basel.

Novel anisotropic engineered cardiac tissues: studies of electrical propagation.

PubMed

Bursac, Nenad; Loo, Yihua; Leong, Kam; Tung, Leslie

2007-10-05

The goal of this study was to engineer cardiac tissue constructs with uniformly anisotropic architecture, and to evaluate their electrical function using multi-site optical mapping of cell membrane potentials. Anisotropic polymer scaffolds made by leaching of aligned sucrose templates were seeded with neonatal rat cardiac cells and cultured in rotating bioreactors for 6-14 days. Cells aligned and interconnected inside the scaffolds and when stimulated by a point electrode, supported macroscopically continuous, anisotropic impulse propagation. By culture day 14, the ratio of conduction velocities along vs. across cardiac fibers reached a value of 2, similar to that in native neonatal ventricles, while action potential duration and maximum capture rate, respectively, decreased to 120ms and increased to approximately 5Hz. The shorter culture time and larger scaffold thickness were associated with increased incidence of sustained reentrant arrhythmias. In summary, this study is the first successful attempt to engineer a cm(2)-size, functional anisotropic cardiac tissue patch.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

PubMed

Moler, Frank W; Silverstein, Faye S; Holubkov, Richard; Slomine, Beth S; Christensen, James R; Nadkarni, Vinay M; Meert, Kathleen L; Browning, Brittan; Pemberton, Victoria L; Page, Kent; Gildea, Marianne R; Scholefield, Barnaby R; Shankaran, Seetha; Hutchison, Jamie S; Berger, John T; Ofori-Amanfo, George; Newth, Christopher J L; Topjian, Alexis; Bennett, Kimberly S; Koch, Joshua D; Pham, Nga; Chanani, Nikhil K; Pineda, Jose A; Harrison, Rick; Dalton, Heidi J; Alten, Jeffrey; Schleien, Charles L; Goodman, Denise M; Zimmerman, Jerry J; Bhalala, Utpal S; Schwarz, Adam J; Porter, Melissa B; Shah, Samir; Fink, Ericka L; McQuillen, Patrick; Wu, Theodore; Skellett, Sophie; Thomas, Neal J; Nowak, Jeffrey E; Baines, Paul B; Pappachan, John; Mathur, Mudit; Lloyd, Eric; van der Jagt, Elise W; Dobyns, Emily L; Meyer, Michael T; Sanders, Ronald C; Clark, Amy E; Dean, J Michael

2017-01-26

Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice

PubMed Central

Belmonte, Stephen L.; Ram, Rashmi; Mickelsen, Deanne M.; Gertler, Frank B.

2013-01-01

Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By “turning off” Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology. PMID:23832697

Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice.

PubMed

Belmonte, Stephen L; Ram, Rashmi; Mickelsen, Deanne M; Gertler, Frank B; Blaxall, Burns C

2013-09-15

Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By "turning off" Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology.

Geranylgeranylacetone blocks doxorubicin-induced cardiac toxicity and reduces cancer cell growth and invasion through RHO pathway inhibition.

PubMed

Sysa-Shah, Polina; Xu, Yi; Guo, Xin; Pin, Scott; Bedja, Djahida; Bartock, Rachel; Tsao, Allison; Hsieh, Angela; Wolin, Michael S; Moens, An; Raman, Venu; Orita, Hajime; Gabrielson, Kathleen L

2014-07-01

Doxorubicin is a widely used chemotherapy for solid tumors and hematologic malignancies, but its use is limited due to cardiotoxicity. Geranylgeranylacetone (GGA), an antiulcer agent used in Japan for 30 years, has no significant adverse effects, and unexpectedly reduces ovarian cancer progression in mice. Because GGA reduces oxidative stress in brain and heart, we hypothesized that GGA would prevent oxidative stress of doxorubicin cardiac toxicity and improve doxorubicin's chemotherapeutic effects. Nude mice implanted with MDA-MB-231 breast cancer cells were studied after chronic treatment with doxorubicin, doxorubicin/GGA, GGA, or saline. Transthoracic echocardiography was used to monitor systolic heart function and xenografts evaluated. Mice were euthanized and cardiac tissue evaluated for reactive oxygen species generation, TUNEL assay, and RHO/ROCK pathway analysis. Tumor metastases were evaluated in lung sections. In vitro studies using Boyden chambers were performed to evaluate GGA effects on RHO pathway activator lysophosphatidic acid (LPA)-induced motility and invasion. We found that GGA reduced doxorubicin cardiac toxicity, preserved cardiac function, prevented TUNEL-positive cardiac cell death, and reduced doxorubicin-induced oxidant production in a nitric oxide synthase-dependent and independent manner. GGA also reduced heart doxorubicin-induced ROCK1 cleavage. Remarkably, in xenograft-implanted mice, combined GGA/doxorubicin treatment decreased tumor growth more effectively than doxorubicin treatment alone. As evidence of antitumor effect, GGA inhibited LPA-induced motility and invasion by MDA-MB-231 cells. These anti-invasive effects of GGA were suppressed by geranylgeraniol suggesting GGA inhibits RHO pathway through blocking geranylation. Thus, GGA protects the heart from doxorubicin chemotherapy-induced injury and improves anticancer efficacy of doxorubicin in breast cancer. ©2014 American Association for Cancer Research.

Role of Oxygen Free Radicals, Nitric Oxide and Mitochondria in Mediating Cardiac Alterations During Liver Cirrhosis Induced by Thioacetamide.

PubMed

Amirtharaj, G Jayakumar; Natarajan, Sathish Kumar; Pulimood, Anna; Balasubramanian, K A; Venkatraman, Aparna; Ramachandran, Anup

2017-04-01

Thioacetamide (TAA) administration is widely used for induction of liver cirrhosis in rats, where reactive oxygen radicals (ROS) and nitric oxide (NO) participate in development of liver damage. Cardiac dysfunction is an important complication of liver cirrhosis, but the role of ROS or NO in cardiac abnormalities during liver cirrhosis is not well understood. This was investigated in animals after TAA-induced liver cirrhosis and temporal changes in oxidative stress, NO and mitochondrial function in the heart evaluated. TAA induced elevation in cardiac levels of nitrate before development of frank liver cirrhosis, without gross histological alterations. This was accompanied by an early induction of P38 MAP kinase, which is influenced by ROS and plays an important signaling role for induction of iNOS. Increased nitrotyrosine, protein oxidation and lipid peroxidation in the heart and cardiac mitochondria, suggestive of oxidative stress, also preceded frank liver cirrhosis. However, compromised cardiac mitochondrial function with a decrease in respiratory control ratio and increased mitochondrial swelling was seen later, when cirrhosis was evident. In conclusion, TAA induces elevations in ROS and NO in the heart in parallel to early liver damage. This leads to later development of functional deficits in cardiac mitochondria after development of liver cirrhosis.

Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease.

PubMed

Tanaka, Kayo; Tanaka, Hiroaki; Maki, Shintaro; Kubo, Michiko; Nii, Masafumi; Magawa, Shoichi; Hatano, Fumi; Tsuji, Makoto; Osato, Kazuhiro; Kamimoto, Yuki; Umekawa, Takashi; Ikeda, Tomoaki

2018-02-20

The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.

PubMed

Scharin Täng, M; Redfors, B; Lindbom, M; Svensson, J; Ramunddal, T; Ohlsson, C; Shao, Y; Omerovic, E

2012-12-01

IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. Copyright © 2012 Elsevier Ltd. All rights reserved.

Macrophage Migration Inhibitory Factor (MIF) Deficiency Exacerbates Aging-Induced Cardiac Remodeling and Dysfunction Despite Improved Inflammation: Role of Autophagy Regulation.

PubMed

Xu, Xihui; Pang, Jiaojiao; Chen, Yuguo; Bucala, Richard; Zhang, Yingmei; Ren, Jun

2016-03-04

Aging leads to unfavorable geometric and functional sequelae in the heart. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) plays a role in the maintenance of cardiac homeostasis under stress conditions although its impact in cardiac aging remains elusive. This study was designed to evaluate the role of MIF in aging-induced cardiac anomalies and the underlying mechanism involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were examined in young (3-4 mo) or old (24 mo) wild type and MIF knockout (MIF(-/-)) mice. Our data revealed that MIF knockout exacerbated aging-induced unfavorable structural and functional changes in the heart. The detrimental effect of MIF knockout was associated with accentuated loss in cardiac autophagy with aging. Aging promoted cardiac inflammation, the effect was attenuated by MIF knockout. Intriguingly, aging-induced unfavorable responses were reversed by treatment with the autophagy inducer rapamycin, with improved myocardial ATP availability in aged WT and MIF(-/-) mice. Using an in vitro model of senescence, MIF knockdown exacerbated doxorubicin-induced premature senescence in H9C2 myoblasts, the effect was ablated by MIF replenishment. Our data indicated that MIF knockout exacerbates aging-induced cardiac remodeling and functional anomalies despite improved inflammation, probably through attenuating loss of autophagy and ATP availability in the heart.

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

Propofol Induction's Effect on Cardiac Function

ClinicalTrials.gov

2015-03-31

This Study Was Focused to Evaluate Feasibility of Doppler Tissue Monitoring During the Induction Anesthesia,; and Evaluate Routine Propofol Induction's Effect on Myocardial Tissue Motion, Using Non-invasive Doppler Tissue and 2D Speckle Tracking Imaging.; This is the First Study, to Our Knowledge, Which Has Evaluated the Possible Impact of Propofol Induction on LV Function.

Cardiomyocyte architectural plasticity in fetal, neonatal, and adult pig hearts delineated with diffusion tensor MRI.

PubMed

Zhang, Lei; Allen, John; Hu, Lingzhi; Caruthers, Shelton D; Wickline, Samuel A; Chen, Junjie

2013-01-15

Cardiomyocyte organization is a critical determinant of coordinated cardiac contractile function. Because of the acute opening of the pulmonary circulation, the relative workload of the left ventricle (LV) and right ventricle (RV) changes substantially immediately after birth. We hypothesized that three-dimensional cardiomyocyte architecture might be required to adapt rapidly to accommodate programmed perinatal changes of cardiac function. Isolated fixed hearts from pig fetuses or pigs at midgestation, preborn, postnatal day 1 (P1), postnatal day 5, postnatal day 14 (P14), and adulthood (n = 5 for each group) were acquired for diffusion-weighted magnetic resonance imaging. Cardiomyocyte architecture was visualized by three-dimensional fiber tracking and was quantitatively evaluated by the measured helix angle (α(h)). Upon the completion of MRI, hearts were sectioned and stained with hematoxylin/eosin (H&E) to evaluate cardiomyocyte alignment, with picrosirius red to evaluate collagen content, and with anti-Ki67 to evaluate postnatal cell proliferation. The helical architecture of cardiomyocyte was observed as early as the midgestational period. Postnatal changes of cardiomyocyte architecture were observed from P1 to P14, which primary occurred in the septum and RV free wall (RVFW). In the septum, the volume ratio of LV- vs. RV-associated cardiomyocytes rapidly changed from RV-LV balanced pattern at birth to LV dominant pattern by P14. In the RVFW, subendocardial α(h) decreased by ~30° from P1 to P14. These findings indicate that the helical architecture of cardiomyocyte is developed as early as the midgestation period. Substantial and rapid adaptive changes in cardiac microarchitecture suggested considerable developmental plasticity of cardiomyocyte form and function in the postnatal period in response to altered cardiac mechanical function.

Cardiomyocyte architectural plasticity in fetal, neonatal, and adult pig hearts delineated with diffusion tensor MRI

PubMed Central

Zhang, Lei; Allen, John; Hu, Lingzhi; Caruthers, Shelton D.; Wickline, Samuel A.

2013-01-01

Cardiomyocyte organization is a critical determinant of coordinated cardiac contractile function. Because of the acute opening of the pulmonary circulation, the relative workload of the left ventricle (LV) and right ventricle (RV) changes substantially immediately after birth. We hypothesized that three-dimensional cardiomyocyte architecture might be required to adapt rapidly to accommodate programmed perinatal changes of cardiac function. Isolated fixed hearts from pig fetuses or pigs at midgestation, preborn, postnatal day 1 (P1), postnatal day 5, postnatal day 14 (P14), and adulthood (n = 5 for each group) were acquired for diffusion-weighted magnetic resonance imaging. Cardiomyocyte architecture was visualized by three-dimensional fiber tracking and was quantitatively evaluated by the measured helix angle (αh). Upon the completion of MRI, hearts were sectioned and stained with hematoxylin/eosin (H&E) to evaluate cardiomyocyte alignment, with picrosirius red to evaluate collagen content, and with anti-Ki67 to evaluate postnatal cell proliferation. The helical architecture of cardiomyocyte was observed as early as the midgestational period. Postnatal changes of cardiomyocyte architecture were observed from P1 to P14, which primary occurred in the septum and RV free wall (RVFW). In the septum, the volume ratio of LV- vs. RV-associated cardiomyocytes rapidly changed from RV-LV balanced pattern at birth to LV dominant pattern by P14. In the RVFW, subendocardial αh decreased by ∼30° from P1 to P14. These findings indicate that the helical architecture of cardiomyocyte is developed as early as the midgestation period. Substantial and rapid adaptive changes in cardiac microarchitecture suggested considerable developmental plasticity of cardiomyocyte form and function in the postnatal period in response to altered cardiac mechanical function. PMID:23161881

Embryonic Stem Cell-Based Cardiopatches Improve Cardiac Function in Infarcted Rats

PubMed Central

Vallée, Jean-Paul; Hauwel, Mathieu; Lepetit-Coiffé, Matthieu; Bei, Wang; Montet-Abou, Karin; Meda, Paolo; Gardier, Stephany; Zammaretti, Prisca; Kraehenbuehl, Thomas P.; Herrmann, Francois; Hubbell, Jeffrey A.

2012-01-01

Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction. PMID:23197784

Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

PubMed

Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

2006-10-03

We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

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

Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia.

PubMed

Vaillant, Fanny; Lauzier, Benjamin; Ruiz, Matthieu; Shi, Yanfen; Lachance, Dominic; Rivard, Marie-Eve; Bolduc, Virginie; Thorin, Eric; Tardif, Jean-Claude; Des Rosiers, Christine

2016-10-01

While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker I f current, vs. β-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB +/+ ;LDLR -/- ). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13 C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. Copyright © 2016 the American Physiological Society.

Bundled Postconditioning Therapies Improve Hemodynamics and Neurologic Recovery after 17 Minutes of Untreated Cardiac Arrest

PubMed Central

Bartos, Jason A.; Matsuura, Timothy R.; Sarraf, Mohammad; Youngquist, Scott T.; McKnite, Scott H.; Rees, Jennifer N.; Sloper, Daniel T.; Bates, Frank S.; Segal, Nicolas; Debaty, Guillaume; Lurie, Keith G.; Neumar, Robert W.; Metzger, Joseph M.; Riess, Matthias L.; Yannopoulos, Demetris

2014-01-01

Objective Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 minutes of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. Methods Following 17 minutes of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. Results Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 hours), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 hours). Conclusions Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 minutes of untreated cardiac arrest in pigs. PMID:25447036

Transplantation of Epigenetically Modified Adult Cardiac c-Kit+ Cells Retards Remodeling and Improves Cardiac Function in Ischemic Heart Failure Model

PubMed Central

Zakharova, Liudmila; Nural-Guvener, Hikmet; Feehery, Lorraine; Popovic-Sljukic, Snjezana

2015-01-01

Cardiac c-Kit+ cells have a modest cardiogenic potential that could limit their efficacy in heart disease treatment. The present study was designed to augment the cardiogenic potential of cardiac c-Kit+ cells through class I histone deacetylase (HDAC) inhibition and evaluate their therapeutic potency in the chronic heart failure (CHF) animal model. Myocardial infarction (MI) was created by coronary artery occlusion in rats. c-Kit+ cells were treated with mocetinostat (MOCE), a specific class I HDAC inhibitor. At 3 weeks after MI, CHF animals were retrogradely infused with untreated (control) or MOCE-treated c-Kit+ cells (MOCE/c-Kit+ cells) and evaluated at 3 weeks after cell infusion. We found that class I HDAC inhibition in c-Kit+ cells elevated the level of acetylated histone H3 (AcH3) and increased AcH3 levels in the promoter regions of pluripotent and cardiac-specific genes. Epigenetic changes were accompanied by increased expression of cardiac-specific markers. Transplantation of CHF rats with either control or MOCE/c-Kit+ cells resulted in an improvement in cardiac function, retardation of CHF remodeling made evident by increased vascularization and scar size, and cardiomyocyte hypertrophy reduction. Compared with CHF infused with control cells, infusion of MOCE/c-Kit+ cells resulted in a further reduction in left ventricle end-diastolic pressure and total collagen and an increase in interleukin-6 expression. The low engraftment of infused cells suggests that paracrine effects might account for the beneficial effects of c-Kit+ cells in CHF. In conclusion, selective inhibition of class I HDACs induced expression of cardiac markers in c-Kit+ cells and partially augmented the efficacy of these cells for CHF repair. Significance The study has shown that selective class 1 histone deacetylase inhibition is sufficient to redirect c-Kit+ cells toward a cardiac fate. Epigenetically modified c-Kit+ cells improved contractile function and retarded remodeling of the congestive heart failure heart. This study provides new insights into the efficacy of cardiac c-Kit+ cells in the ischemic heart failure model. PMID:26240433

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

Pulmonary function and health-related quality of life 1-year follow up after cardiac surgery.

PubMed

Westerdahl, Elisabeth; Jonsson, Marcus; Emtner, Margareta

2016-07-08

Pulmonary function is severely reduced in the early period after cardiac surgery, and impairments have been described up to 4-6 months after surgery. Evaluation of pulmonary function in a longer perspective is lacking. In this prospective study pulmonary function and health-related quality of life were investigated 1 year after cardiac surgery. Pulmonary function measurements, health-related quality of life (SF-36), dyspnoea, subjective breathing and coughing ability and pain were evaluated before and 1 year after surgery in 150 patients undergoing coronary artery bypass grafting, valve surgery or combined surgery. One year after surgery the forced vital capacity and forced expiratory volume in 1 s were significantly decreased (by 4-5 %) compared to preoperative values (p < 0.05). Saturation of peripheral oxygen was unchanged 1 year postoperatively compared to baseline. A significantly improved health-related quality of life was found 1 year after surgery, with improvements in all eight aspects of SF-36 (p < 0.001). Sternotomy-related pain was low 1 year postoperatively at rest (median 0 [min-max; 0-7]), while taking a deep breath (0 [0-4]) and while coughing (0 [0-8]). A more pronounced decrease in pulmonary function was associated with dyspnoea limitations and impaired subjective breathing and coughing ability. One year after cardiac surgery static and dynamic lung function measurements were slightly decreased, while health-related quality of life was improved in comparison to preoperative values. Measured levels of pain were low and saturation of peripheral oxygen was same as preoperatively.

Evaluation of left ventricular function by bedside ultrasound in acute toxic myocarditis.

PubMed

Brown, Cara; Budhram, Gavin

2013-10-01

Myocarditis can be difficult to diagnose in the Emergency Department (ED) due to the lack of classic symptoms and the wide variation in presentations. Poor cardiac contractility is a common finding in myocarditis and can be evaluated by bedside ultrasound. To demonstrate the utility of fractional shortening measurements as an estimation of left ventricular function during bedside cardiac ultrasound evaluation in the ED. A 54-year-old man presented to the ED complaining of 3 days of chest tightness, palpitations, and dyspnea, as well as persistent abdominal pain and vomiting. An electrocardiogram (ECG) showed sinus tachycardia with presumably new ST-segment elevation and signs of an incomplete right bundle branch block. A bedside echocardiogram was performed by the emergency physician that showed poor left ventricular function by endocardial fractional shortening measurements. On further questioning, the patient revealed that for the past 2 weeks he had been regularly huffing a commercially available compressed air duster. Based on these history and examination findings, the patient was given a presumptive diagnosis of toxic myocarditis. A follow-up echocardiogram approximately 7 weeks later demonstrated resolution of the left ventricular systolic dysfunction and his ECG findings normalized. Cardiac ultrasound findings of severely reduced global function measured by endocardial fractional shortening were seen in this patient and supported the diagnosis of myocarditis. Endocardial fractional shortening is a useful means of easily evaluating and documenting left ventricular function and can be performed at the bedside in the ED. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

PubMed

Liang, Zhongshu; Leo, Sunnar; Wen, Helin; Ouyang, Mao; Jiang, Weihong; Yang, Kan

2015-05-13

Triptolide treatment leads to an improvement in Diabetic Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is characterized by abnormal cardiac energy metabolism. We hypothesized that triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac energy metabolism in vivo and evaluating the effect of triptolide treatment in DCM rats. Six weeks triptolide treatment was conducted on streptozotocin-induced diabetic rats with dose of 100, 200 or 400 μg/kg/day respectively. Sex- and age-matched non-diabetic rats were used as control group. Cardiac chamber dimension and function were determined with echocardiography. Whole heart preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured using real time PCR and western blot analysis. In diabetic rats, cardiac mass index was significantly higher, where as cardiac EF was lower than control group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic groups were also remarkably lower than control group. Compared to non-treated diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best improvement was seen in group treated with Triptolide with dose 200 μg/kg/day. (31)P NMR spectroscopy enables assessment of cardiac energy metabolism in whole heart preparations. It detects energy metabolic abnormalities in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac energy metabolism at least partly through upregulation of MAPK signaling transduction.

Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.

PubMed

Kuo, Anderson H; Li, Cun; Li, Jinqi; Huber, Hillary F; Nathanielsz, Peter W; Clarke, Geoffrey D

2017-02-15

Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non-human primate model. Further studies across the life span will determine progression of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

[A basis for application of cardiac contractility variability in the Evaluation and assessment of exercise and fitness].

PubMed

Bu, Bin; Wang, Aihua; Han, Haijun; Xiao, Shouzhong

2010-06-01

Cardiac contractility variability (CCV) is a new concept which is introduced in the research field of cardiac contractility in recent years, that is to say, there are some disparities between cardiac contractilities when heart contracts. The changing signals of cardiac contractility contain a plenty of information on the cardiovascular function and disorder. In order to collect and analyze the message, we could quantitatively evaluate the tonicity and equilibrium of cardiac sympathetic nerve and parasympathetic nerve, and the effects of bio-molecular mechanism on the cardiovascular activities. By analyzing CCV, we could further understand the background of human being's heritage characteristics, nerve types, the adjusting mechanism, the molecular biology, and the adjustment of cardiac automatic nerve. With the development of the computing techniques, the digital signal processing method and its application in medical field, this analysis has been progressing greatly. By now, the assessment of CCV, just like the analysis of heart rate variability, is mainly via time domain and frequency domain analysis. CCV is one of the latest research fields in human cardiac signals being scarcely reported in the field of sports medicine; however, its research progresses are of important value for cardiac physiology and pathology in sports medicine and rehabilitation medicine.

ACR-SPR-STR Practice Parameter for the Performance of Cardiac Positron Emission Tomography - Computed Tomography (PET/CT) Imaging.

PubMed

Subramaniam, Rathan M; Janowitz, Warren R; Johnson, Geoffrey B; Lodge, Martin A; Parisi, Marguerite T; Ferguson, Mark R; Hellinger, Jeffrey C; Gladish, Gregory W; Gupta, Narainder K

2017-12-01

This clinical practice parameter has been developed collaboratively by the American College of Radiology (ACR), the Society for Pediatric Radiology (SPR), and the Society of Thoracic Radiology (STR). This document is intended to act as a guide for physicians performing and interpreting positron emission tomography-computed tomography (PET/CT) of cardiac diseases in adults and children. The primary value of cardiac PET/CT imaging include evaluation of perfusion, function, viability, inflammation, anatomy, and risk stratification for cardiac-related events such as myocardial infarction and death. Optimum utility of cardiac PET/CT is achieved when images are interpreted in conjunction with clinical information and laboratory data. Measurement of myocardial blood flow, coronary flow reserve and detection of balanced ischemia are significant advantages of cardiac PET perfusion studies. Increasingly cardiac PET/CT is used in diagnosis and treatment response assessment for cardiac sarcoidosis.

Standardization of the two-dimensional transcoelomic echocardiographic examination in the central bearded dragon (Pogona vitticeps).

PubMed

Silverman, S; Sanchez-Migallon Guzman, D; Stern, J; Gustavsen, K A; Griffiths, L G

2016-06-01

To objectively and subjectively describe the normal spectrum of two-dimensional echocardiographic findings in the central bearded dragon (Pogona vitticeps). Sixteen central bearded dragons. Central bearded dragons were prospectively evaluated under manual restraint in right and left lateral recumbency to identify imaging planes for reproducible measurements of cardiac chambers, subjective two-dimensional analysis and color Doppler assessment. Echocardiography can be performed through windows in the left and right axillae. The window in the left axilla allows for a subjective and objective assessment of cardiac structure and function. The right axillary window allows for evaluation of pulmonary artery flow. Both views provide data for the presence of pericardial effusion or valvular insufficiency. With optimized imaging planes, cardiac chambers and fractional area change along with fractional shortening in the longitudinal and transverse planes can be calculated. Body weight and cardiac chamber dimensions of males were significantly larger than females. Ventricular fractional area change was the most consistent functional assessment. The majority of animals were found to have no evidence of valvular insufficiency, while approximately half had evidence of pericardial fluid. Pulmonary artery flow was assessed in all patients. Left and right aortic velocities cannot be reliably obtained. This study is the first to generate reference values for cardiac structure and function in clinically healthy central bearded dragons. Valvular insufficiency is not a normal finding in central bearded dragons, while mild pericardial effusion may be. Copyright © 2015 Elsevier B.V. All rights reserved.

Cathepsin K knockout alleviates aging-induced cardiac dysfunction

PubMed Central

Hua, Yinan; Robinson, Timothy J; Cao, Yongtao; Shi, Guo-Ping; Ren, Jun; Nair, Sreejayan

2015-01-01

Aging is a major risk factor for cardiovascular disease. It has previously been shown that protein levels of cathepsin K, a lysosomal cysteine protease, are elevated in the failing heart and that genetic ablation of cathepsin K protects against pressure overload-induced cardiac hypertrophy and contractile dysfunction. Here we test the hypothesis that cathepsin K knockout alleviates age-dependent decline in cardiac function. Cardiac geometry, contractile function, intracellular Ca2+ properties, and cardiomyocyte apoptosis were evaluated using echocardiography, fura-2 technique, immunohistochemistry, Western blot and TUNEL staining, respectively. Aged (24-month-old) mice exhibited significant cardiac remodeling (enlarged chamber size, wall thickness, myocyte cross-sectional area, and fibrosis), decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca2+ release compared to young (6-month-old) mice, which were attenuated in the cathepsin K knockout mice. Cellular markers of senescence, including cardiac lipofuscin, p21 and p16, were lower in the aged-cathepsin K knockout mice compared to their wild-type counterpart. Mechanistically, cathepsin K knockout mice attenuated an age-induced increase in cardiomyocyte apoptosis and nuclear translocation of mitochondrial apoptosis-inducing factor (AIF). In cultured H9c2 cells, doxorubicin stimulated premature senescence and apoptosis. Silencing of cathepsin K blocked the doxorubicin-induced translocation of AIF from the mitochondria to the nuclei. Collectively, these results suggest that cathepsin K knockout attenuates age-related decline in cardiac function via suppressing caspase-dependent and caspase-independent apoptosis. PMID:25692548

Cardiac rehabilitation and mid-term follow-up after transcatheter aortic valve implantation

PubMed Central

Zanettini, Renzo; Gatto, Gemma; Mori, Ileana; Pozzoni, Maria Beatrice; Pelenghi, Stefano; Martinelli, Luigi; Klugmann, Silvio

2014-01-01

Background Evaluation of patient outcomes following transcatheter aortic valve implantation (TAVI) has usually been based on survival and clinical improvement. Studies on quality of life are limited, and data from comprehensive assessments after the procedure are lacking. Methods Sixty patients referred for cardiac rehabilitation after TAVI underwent in-hospital and after-discharge multidimensional assessments to evaluate clinical, functional, and nutritional statuses, degree of autonomy, cognitive impairment, depression and quality of life. Results On admission to rehabilitation, approximately half of the patients had severe functional impairment and dependence for basic activities of daily living. During their hospital stay, one-third of the patients suffered significant clinical complications and two had to be transferred to the implantation center. Despite this, the overall outcome was very good. All of the remaining patients were clinically stable at discharge and functional status, autonomy and quality of life were improved in most. During a mean follow-up of 540 days (range: 192–738 days), five patients died from noncardiac causes, three were hospitalized for cardiac events, and nine for non cardiac reasons. Functional status and autonomy remained satisfactory in the majority of patients and most continued to live independently. Conclusions Patients referred for rehabilitation after TAVI are often very frail, with a high grade of functional impairment, dependence on others and high risk of clinical complications. During a rehabilitation programme, based on a multidimensional assessment and intervention, most patients showed significant improvement in functional status, quality of life, and autonomy, which remained stable in the majority of subjects during mid-term follow-up. PMID:25593575

Incentive spirometry in major surgeries: a systematic review.

PubMed

Carvalho, Celso R F; Paisani, Denise M; Lunardi, Adriana C

2011-01-01

To conduct a systematic review to evaluate the evidence of the use of incentive spirometry (IS) for the prevention of postoperative pulmonary complications and for the recovery of pulmonary function in patients undergoing abdominal, cardiac and thoracic surgeries. Searches were performed in the following databases: Medline, Embase, Web of Science, PEDro and Scopus to select randomized controlled trials which the IS was used in pre- and/or post-operative in order to prevent postoperative pulmonary complications and/or recover lung function after abdominal, cardiac and thoracic surgery. Two reviewers independently assessed all studies. In addition, the studies quality was assessed using the PEDro scale. Thirty studies were included (14 abdominal, 13 cardiac and 3 thoracic surgery; n=3,370 patients). In the analysis of the methodological quality, studies achieved a PEDro average score of 5.6, 4.7 and 4.8 points in abdominal, cardiac and thoracic surgeries, respectively. Five studies (3 abdominal, 1 cardiac and 1 thoracic surgery) compared the effect of the IS with control group (no intervention) and no difference was detected in the evaluated outcomes. There was no evidence to support the use of incentive spirometry in the management of surgical patients. Despite this, the use of incentive spirometry remains widely used without standardization in clinical practice.

Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β-adrenergic system and does not compromise cardiac function.

PubMed

Vileigas, Danielle F; de Deus, Adriana F; da Silva, Danielle C T; de Tomasi, Loreta C; de Campos, Dijon H S; Adorni, Caroline S; de Oliveira, Scarlet M; Sant'Ana, Paula G; Okoshi, Katashi; Padovani, Carlos R; Cicogna, Antonio C

2016-09-01

Obesity is a worldwide pandemic associated with high incidence of cardiovascular disease. The mechanisms by which the obesity leads cardiac dysfunction are not fully elucidated and few studies have evaluated the relationship between obesity and proteins involved in myocardial β-adrenergic (βA) system. The purpose of this study was to evaluate the cardiac function and βA pathway components in myocardium of obese rats. Male Wistar rats were distributed into two groups: control (n = 17; standard diet) and obese (n = 17; saturated high-fat diet) fed for 33 weeks. Nutritional profile and comorbidities were assessed. Cardiac structure and function was evaluated by macroscopic postmortem, echocardiographic and isolated papillary muscle analyzes. Myocardial protein expression of β1- and β2-adrenergic receptors, Gαs protein, adenylate cyclase (AC) and protein kinase A (PKA) was performed by Western blot. Cardiac cyclic adenosine monophosphate (cAMP) levels and PKA activity were assessed by ELISA Obese rats showed increased adiposity index (P < 0.001) and several comorbidities as hypertension, glucose intolerance, insulin resistance, and dyslipidemia compared with control rats. Echocardiographic assessment revealed increased left atrium diameter (C: 4.98 ± 0.38 vs. Ob: 5.47 ± 0.53, P = 0.024) and posterior wall shortening velocity (C: 37.1 ± 3.6 vs. Ob: 41.8 ± 3.8, P = 0.007) in obese group. Papillary muscle evaluation indicated that baseline data and myocardial responsiveness to isoproterenol stimulation were similar between the groups. Protein expression of myocardial AC was higher in obese group than in the control (C: 1.00 ± 0.21 vs. Ob: 1.25 ± 0.10, P = 0.025), whereas the other components were unchanged. These results suggest that saturated high-fat diet-induced obesity was not effective in triggering cardiac dysfunction and impair the beta-adrenergic signaling. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling

PubMed Central

de Sá, Felipe Gonçalves dos Santos; Lima-Leopoldo, Ana Paula; Jacobsen, Bruno Barcellos; Ferron, Artur Junio Togneri; Estevam, Wagner Muller; Campos, Dijon Henrique Salomé; Castardeli, Edson; da Cunha, Márcia Regina Holanda; Cicogna, Antonio Carlos; Leopoldo, André Soares

2015-01-01

Background Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. Objective To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Methods Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. Results The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Conclusion Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling. PMID:26761369

Electrical and mechanical stimulation of cardiac cells and tissue constructs.

PubMed

Stoppel, Whitney L; Kaplan, David L; Black, Lauren D

2016-01-15

The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

Novel cardiac protective effects of urea: from shark to rat

PubMed Central

Wang, Xintao; Wu, Lingyun; Aouffen, M'hamed; Mateescu, Mircea-Alexandru; Nadeau, Réginald; Wang, Rui

1999-01-01

This study was carried out to investigate novel cardioprotective effects of urea and the underlying mechanisms. The cardiac functions under oxidative stress were evaluated using Langendorff perfused isolated heart.Isolated dogfish shark hearts tolerated the oxidative stress generated by electrolysis (10 mA, 1 min) of the perfusion solution (n=4), and also showed normal cardiac functions during post-ischaemia reperfusion (n=4). The high concentration of urea (350 mM) in the heart perfusate was indispensable for maintaining the normal cardiac functions of the shark heart.Urea at 3–300 mM (n=4 for each group) protected the isolated rat heart against both electrolysis-induced heart damage and post-ischaemia reperfusion-induced cardiac injury.A concentration-dependent scavenging effect of urea (3–300 mM, n=4 for each group) against electrolysis-induced reactive oxygen species was also demonstrated in vitro.Urea derivatives as hydroxyurea, dimethylurea, and thiourea had antioxidant cardioprotective effect against the electrolysis-induced cardiac dysfunction of rat heart, but were not as effective as urea in suppressing the post-ischaemia reperfusion injury.Our results suggest that urea and its derivatives are potential antioxidant cardioprotective agents against oxidative stress-induced myocardium damage including the post-ischaemia reperfusion-induced injury. PMID:10602326

Acupuncture Effects on Cardiac Functions Measured by Cardiac Magnetic Resonance Imaging in a Feline Model

PubMed Central

Lin, Jen-Hsou; Shih, Chen-Haw; Kaphle, Krishna; Wu, Leang-Shin; Tseng, Weng-Yih; Chiu, Jen-Hwey; Lee, Tzu-chi

2010-01-01

The usefulness of acupuncture (AP) as a complementary and/or alternative therapy in animals is well established but more research is needed on its clinical efficacy relative to conventional therapy, and on the underlying mechanisms of the effects of AP. Cardiac magnetic resonance imaging (CMRI), an important tool in monitoring cardiovascular diseases, provides a reliable method to monitor the effects of AP on the cardiovascular system. This controlled experiment monitored the effect electro-acupuncture (EA) at bilateral acupoint Neiguan (PC6) on recovery time after ketamine/xylazine cocktail anesthesia in healthy cats. The CMRI data established the basic feline cardiac function index (CFI), including cardiac output and major vessel velocity. To evaluate the effect of EA on the functions of the autonomic nervous and cardiovascular systems, heart rate, respiration rate, electrocardiogram and pulse rate were also measured. Ketamine/xylazine cocktail anesthesia caused a transient hypertension in the cats; EA inhibited this anesthetic-induced hypertension and shortened the post-anesthesia recovery time. Our data support existing knowledge on the cardiovascular benefits of EA at PC6, and also provide strong evidence for the combination of anesthesia and EA to shorten post-anesthesia recovery time and counter the negative effects of anesthetics on cardiac physiology. PMID:18955311

Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function

PubMed Central

Beaumont, Eric; Salavatian, Siamak; Southerland, E Marie; Vinet, Alain; Jacquemet, Vincent; Armour, J Andrew; Ardell, Jeffrey L

2013-01-01

The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias. PMID:23818689

Short-term effects of β2-AR blocker ICI 118,551 on sarcoplasmic reticulum SERCA2a and cardiac function of rats with heart failure.

PubMed

Gong, Haibin; Li, Yanfei; Wang, Lei; Lv, Qian; Wang, Xiuli

2016-09-01

The study was conducted to examine the effects of ICI 118,551 on the systolic function of cardiac muscle cells of rats in heart failure and determine the molecular mechanism of selective β2-adrenergic receptor (β2-AR) antagonist on these cells. The chronic heart failure model for rats was prepared through abdominal aortic constriction and separate cardiac muscle cells using the collagenase digestion method. The rats were then divided into Sham, HF and HF+ICI 50 nM goups and cultivated for 48 h. β2-AR, Gi/Gs and sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2a) protein expression levels in the cardiac muscle cells were evaluated by western blotting and changes in the systolic function of cardiac muscle cells based on the boundary detection system of contraction dynamics for individual cells was measured. The results showed that compared with the Sham group, the survival rate, percentage of basic contraction and maximum contraction amplitude percentage of cardiac muscle cells with heart failure decreased, Gi protein expression increased while Gs and SERCA2a protein expression decreased. Compared with the HF group, the maximum contraction amplitude percentage of cardiac muscle cells in group HF+ICI 50 nM decreased, the Gi protein expression level increased while the SERCA2a protein expression level decreased. Following the stimulation of Ca 2+ and ISO, the maximum contraction amplitude percentage of cardiac muscle cells in the HF+ICI 50 nM group was lower than that in group HF. This indicated that ICI 118,551 has negative inotropic effects on cardiac muscle cells with heart failure, which may be related to Gi protein. Systolic function of cardiac muscle cells with heart failure can therefore be reduced by increasing Gi protein expression and lowering SERCA2a protein expression.

A home-based exercise program for children with congenital heart disease following interventional cardiac catheterization: study protocol for a randomized controlled trial.

PubMed

Du, Qing; Salem, Yasser; Liu, Hao Howe; Zhou, Xuan; Chen, Sun; Chen, Nan; Yang, Xiaoyan; Liang, Juping; Sun, Kun

2017-01-23

Cardiac catheterization has opened an innovative treatment field for cardiac disease; this treatment is becoming the most popular approach for pediatric congenital heart disease (CHD) and has led to a significant growth in the number of children with cardiac catheterization. Unfortunately, based on evidence, it has been demonstrated that the majority of children with CHD are at an increased risk of "non-cardiac" problems. Effective exercise therapy could improve their functional status significantly. As studies identifying the efficacy of exercise therapy are rare in this field, the aims of this study are to (1) identify the efficacy of a home-based exercise program to improve the motor function of children with CHD with cardiac catheterization, (2) reduce parental anxiety and parenting burden, and (3) improve the quality of life for parents whose children are diagnosed with CHD with cardiac catheterization through the program. A total of 300 children who will perform a cardiac catheterization will be randomly assigned to two groups: a home-based intervention group and a control group. The home-based intervention group will carry out a home-based exercise program, and the control group will receive only home-based exercise education. Assessments will be undertaken before catheterization and at 1, 3, and 6 months after catheterization. Motor ability quotients will be assessed as the primary outcomes. The modified Ross score, cardiac function, speed of sound at the tibia, functional independence of the children, anxiety, quality of life, and caregiver burden of their parents or the main caregivers will be the secondary outcome measurements. The proposed prospective randomized controlled trial will evaluate the efficiency of a home-based exercise program for children with CHD with cardiac catheterization. We anticipate that the home-based exercise program may represent a valuable and efficient intervention for children with CHD and their families. http://www.chictr.org.cn/ on: ChiCTR-IOR-16007762 . Registered on 13 January 2016.

Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.

PubMed

Eirin, Alfonso; Zhu, Xiang-Yang; Ferguson, Christopher M; Riester, Scott M; van Wijnen, Andre J; Lerman, Amir; Lerman, Lilach O

2015-01-19

Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated. PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis. Intra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.

Poor preoperative nutritional status is an important predictor of the retardation of rehabilitation after cardiac surgery in elderly cardiac patients.

PubMed

Ogawa, Masato; Izawa, Kazuhiro P; Satomi-Kobayashi, Seimi; Kitamura, Aki; Ono, Rei; Sakai, Yoshitada; Okita, Yutaka

2017-04-01

Preoperative nutritional status and physical function are important predictors of mortality and morbidity after cardiac surgery. However, the influence of nutritional status before cardiac surgery on physical function and the progress of postoperative rehabilitation requires clarification. To determine the effect of preoperative nutritional status on preoperative physical function and progress of rehabilitation after elective cardiac surgery. We enrolled 131 elderly patients with mean age of 73.7 ± 5.8 years undergoing cardiac surgery. We divided them into two groups by nutritional status as measured by the Geriatric Nutritional Risk Index (GNRI): high GNRI group (GNRI ≥ 92, n = 106) and low GNRI group (GNRI < 92, n = 25). Physical function was estimated by handgrip strength, knee extensor muscle strength (KEMS), the Short Physical Performance Battery (SPPB), and 6-minute walk test (6MWT). Progress of postoperative rehabilitation was evaluated by the number of days to independent walking after surgery, length of stay in the ICU, and length of hospital stay. After adjusting for potential confounding factors, preoperative handgrip strength (P = 0.034), KEMS (P = 0.009), SPPB (P < 0.0001), and 6MWT (P = 0.012) were all significantly better in the high GNRI group. Multiple regression analysis revealed that a low GNRI was an independent predictor of the retardation of postoperative rehabilitation. Preoperative nutritional status as assessed by the GNRI could reflect perioperative physical function. Preoperative poor nutritional status may be an independent predictor of the retardation of postoperative rehabilitation in patients undergoing elective cardiac surgery.

Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall.

PubMed

Wang, Ting; Miller, Kenneth E

2016-08-04

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia (ICG) for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside ICG. In the present study, rat ICG neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) ICG contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial ICG contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT; (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Integrated approach to ischemic heart disease. The one-stop shop.

PubMed

Kramer, C M

1998-05-01

Magnetic resonance imaging is unique in its variety of applications for imaging the cardiovascular system. A thorough assessment of myocardial structure, function, and perfusion; assessment of coronary artery anatomy and flow; and spectroscopic evaluation of cardiac energetics can be readily performed by magnetic resonance imaging. One key to the advancement of cardiac magnetic resonance imaging as a clinical tool in the evaluation, the so called one stop shop. Improvements in magnetic resonance hardware, software, and imaging speed now permit this integrated examination. Cardiac magnetic resonance is a powerful technique with the potential to replace or complement other commonly used techniques in the diagnostic armamentarium of physicians caring for patients with ischemic heart disease.

Cardiac involvement in ANCA (+) and ANCA (-) Churg-Strauss syndrome evaluated by cardiovascular magnetic resonance.

PubMed

Mavrogeni, Sophie; Karabela, Georgia; Gialafos, Elias; Stavropoulos, Efthymios; Spiliotis, George; Katsifis, Gikas; Kolovou, Genovefa

2013-10-01

The cardiovascular magnetic resonance (CMR) pattern of Churg-Strauss syndrome (CSS) includes myopericarditis, diffuse subendocardial vasculitis or myocardial infarction with or without cardiac symptoms and is usually associated with lack of antineutrophil cytoplasmic antibodies (ANCA). To correlate the CMR pattern with ANCA in CSS, compare it with healthy controls and systemic lupus erythematosus (SLE) patients and re-evaluate 2 yrs after the first CMR. 28 consecutive CSS, aged 42±7 yrs, were referred for CMR and 2 yrs re-evaluation. The CMR included left ventricular ejection fraction (LVEF), T2-weighted (T2-W), early (EGE) and late gadolinium enhanced (LGE) imaging. Their results were compared with 28 systemic lupus erythematosus (SLE) under remission and 28 controls with normal myocardial perfusion, assessed by scintigraphy. CMR revealed acute cardiac lesions in all ANCA (-) CSS with active disease and acute cardiac symptoms and only in one asymptomatic ANCA (+) CSS, with active disease. Diffuse subendocardial fibrosis (DSF) or past myocarditis was identified in both ANCA(+) and ANCA (-) CSS, but with higher incidence and fibrosis amount in ANCA (-) CSS (p<0.05). In comparison to SLE, both ANCA (+) and ANCA (-) CSS had higher incidence of DSF, lower incidence of myocarditis and no evidence of myocardial infarction, due to coronary artery disease (p<0.05). In 2 yrs CMR follow up, 1/3 of CSS with DSF presented LV function deterioration and one died, although immunosuppressive treatment was given early after CSS diagnosis. Cardiac involvement either as DSF or myocarditis, can be detected in both ANCA (+) and ANCA (-) CSS, although more clinically overt in ANCA (-). DSF carries an ominous prognosis for LV function. CMR, due to its capability to detect disease severity, before cardiac dysfunction takes place, is an excellent tool for CSS risk stratification and treatment individualization.

Physical activity and cardiac function in the oldest old.

PubMed

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

2012-02-01

The relationship of physical activity (PA) and cardiac function in the oldest old remains unclear. The objective of this study was to evaluate the relationship between PA and cardiac structure and function, in the oldest old. Subjects were recruited from the Jerusalem Longitudinal Cohort Study that was initiated in 1990 and has followed an age homogeneous cohort of Jerusalem residents born in 1920-1921. A total of 496 of the subjects from the most recent set of data collection in 2005-2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. Standard echocardiographic assessment of cardiac structure and function including ejection fraction (EF) and diastolic function as assessed by E:E' measurements was performed. PA was defined as a dichotomous (≥4 hr of light exercise weekly) and as a categorical variable (<4 hr weekly/4 hours weekly/at least 1 hr daily/sport at least twice weekly). On bivariate analysis, mean EF was lower among sedentary versus active women (55.5%±8.5% vs. 58.4%±8.3, p=0.021). No other significant differences were observed between sedentary and active subjects, for either systolic or diastolic function. After adjusting for sex, education, diabetes, ischemic heart disease, hypertension, dependence in activities of daily living, and body mass index (BMI), no significant associations were found between systolic or diastolic function, or left ventricular structure and PA. Gender-specific analyses yielded similar findings. Our study of the oldest old did not demonstrate an association between PA and cardiac structure or function.

Long-term cardiovascular evaluation of patients with Hodgkin's disease treated by thoracic mantle radiation therapy

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

Applefeld, M.M.; Slawson, R.G.; Spicer, K.M.

1982-04-01

The long-term cardiac effects of anterior-weighted thoracic mantle field radiotherapy were assessed in 25 patients treated for Hodgkin's disease. These patients underwent an evaluation that included a careful history and physical examination, ECG, M-mode echocardiogram, exercise ECG-gated radionuclide ventriculography, and cardiac catheterization. In these 25 patients evaluated 37-144 months (median, 96) after completion of thoracic mantle radiotherapy, eight had constrictive pericarditis; eight had occult constrictive pericarditis; three had an abnormal response to fluid challenge; three had suspected or proven occlusive coronary artery disease; and one each had a cardiomyopathy and diminished functional capacity on exercise testing. Only one patient appearsmore » to be normal after evaluation. The clinical spectrum of delayed-appearing radiation-induced cardiac disease in patients treated by anterior-weighted thoracic mantle fields and our suggestions for its treatment are discussed.« less

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

Biventricular Heart Remodeling After Percutaneous or Surgical Pulmonary Valve Implantation: Evaluation by Cardiac Magnetic Resonance.

PubMed

Secchi, Francesco; Resta, Elda C; Cannaò, Paola M; Pluchinotta, Francesca; Piazza, Luciane; Butera, Gianfranco; Carminati, Mario; Sardanelli, Francesco

2017-11-01

The aim of this study was to evaluate the impact of percutaneous pulmonary valve implantation (PPVI) and surgical pulmonary valve replacement (SPVR) on biventricular and pulmonary valve function using cardiac magnetic resonance. Thirty-five patients aged 20±8 years (mean±SD) underwent PPVI, whereas 16 patients aged 30±11 years underwent SPVR. Cardiac magnetic resonance examinations were performed before and after the procedures with an average follow-up interval of 10 months. Cine steady-state free precession sequences for cardiac function and phase-contrast sequences for pulmonary flow were performed. The right ventricle (RV) and left ventricle (LV) functions were evaluated using a dedicated software. The RV end-diastolic volume index (mL/m) decreased significantly after PPVI and SPVR, from 74 to 64 (P=0.030) and from 137 to 83 (P=0.001), respectively. The RV ejection fraction increased significantly after SPVR, from 47% to 53% (P=0.038). The LV end-diastolic volume index increased significantly after PPVI, from 66 to 76 mL/m (P<0.001). The LV stroke volume index increased significantly after PPVI, from 34 to 43 mL/m (P=0.004). The analysis of bivariate correlations showed that in patients undergoing SPVR the RV changes after the procedure were positively correlated to LV changes in terms of end-systolic volume index (r=0587; P=0.017) and ejection fraction (r=0.681; P=0.004). A RV volumetric reduction and a positive effect on ventricular-ventricular interaction were observed after both PPVI and SPVR. After PPVI, a positive volumetric LV remodeling was found. No LV remodeling was found after SPVR. After both procedures, the replaced pulmonary valve functioned well.

Influence of renal impairment on myocardial function in outpatients with systolic heart failure: an echocardiographic and cardiac biomarker study.

PubMed

Bosselmann, Helle; Tonder, Niels; Sölétormos, György; Rossing, Kasper; Iversen, Kasper; Goetze, Jens P; Gustafsson, Finn; Schou, Morten

2014-12-20

Renal dysfunction (RD) is associated with poor outcome in systolic heart failure (HF). Left ventricular ejection fraction (LVEF) is not depressed to a greater extent in patients with RD compared to patients with normal renal function, but it is relatively unknown whether other measures of myocardial function are impaired by RD. The objective of the present study is to evaluate whether RD in systolic HF is associated with excessive impairment of myocardial function, evaluated by strain analysis and cardiac biomarkers. Patients with LVEF <0.45% were enrolled from an outpatient HF clinic. The patients underwent advanced echocardiography. Glomerular filtration rate was estimated by the CKD-EPI equation (eGFR) and patients grouped by eGFR: eGFR group-I, ≥ 90 ml/min/1.73 m(2); eGFR group-II, 60-89 ml/min/1.73 m(2); and eGFR group-III, ≤ 59 ml/min/1.73 m(2). Multivariate regression models were developed to evaluate the associations between eGFR groups, echocardiographic measures and cardiac biomarkers. A total of 149 patients participated in the study. Median age was 69 years, 26% were female; LVEF was 33%. Patients with a low eGFR were older (P < 0.001), but there were no differences in frequency of atrial fibrillation, hypertension, diabetes and ischemic heart disease between eGFR groups (P > 0.05 for all). RD was associated with impaired global longitudinal strain (P = 0.018), increased E/e' (P = 0.032), larger left atria (P = 0.038) and increased levels of proANP (P < 0.001), NT-proBNP (P < 0.001) and troponin I (P = 0.019) after adjustment for traditional confounders. Echocardiographic measures and biomarkers reflecting different aspects of myocardial function are impaired in systolic HF patients with RD and the increased mortality risk in these patients may partly be explained by a depressed cardiac function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Spontaneous Reduction in Abnormal Myocardial Uptake of Fluorine-18 Fluorodeoxygluose in a Patient with Cardiac Sarcoidosis.

PubMed

Terasaki, Fumio; Fujita, Shu-Ichi; Kanzaki, Yumiko; Hirose, Yoshinobu; Ishizaka, Nobukazu

2018-05-30

Fluorine-18 fluorodeoxygluose ( 18 F-FDG) positron emission tomography (PET) is a useful tool for evaluating disease activity in sarcoidosis including cardiac involvement. A 67-year-old patient who developed atrioventricular block requiring permanent pacemaker implantation was diagnosed with cardiac sarcoidosis. The patient did not undergo steroid or immunosuppressive therapy but underwent serial 18 F-FDG PET examination, which showed spontaneous reduction in the myocardial FDG uptake, indicating the remission of immune-inflammatory activity. Although the global systolic function remained preserved, thinning of the septal wall emerged during the clinical course of follow-up, which is characteristic for cardiac sarcoidosis.

Right ventricle functional parameters estimation in arrhythmogenic right ventricular dysplasia using a robust shape based deformable model.

PubMed

Oghli, Mostafa Ghelich; Dehlaghi, Vahab; Zadeh, Ali Mohammad; Fallahi, Alireza; Pooyan, Mohammad

2014-07-01

Assessment of cardiac right-ventricle functions plays an essential role in diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). Among clinical tests, cardiac magnetic resonance imaging (MRI) is now becoming the most valid imaging technique to diagnose ARVD. Fatty infiltration of the right ventricular free wall can be visible on cardiac MRI. Finding right-ventricle functional parameters from cardiac MRI images contains segmentation of right-ventricle in each slice of end diastole and end systole phases of cardiac cycle and calculation of end diastolic and end systolic volume and furthermore other functional parameters. The main problem of this task is the segmentation part. We used a robust method based on deformable model that uses shape information for segmentation of right-ventricle in short axis MRI images. After segmentation of right-ventricle from base to apex in end diastole and end systole phases of cardiac cycle, volume of right-ventricle in these phases calculated and then, ejection fraction calculated. We performed a quantitative evaluation of clinical cardiac parameters derived from the automatic segmentation by comparison against a manual delineation of the ventricles. The manually and automatically determined quantitative clinical parameters were statistically compared by means of linear regression. This fits a line to the data such that the root-mean-square error (RMSE) of the residuals is minimized. The results show low RMSE for Right Ventricle Ejection Fraction and Volume (≤ 0.06 for RV EF, and ≤ 10 mL for RV volume). Evaluation of segmentation results is also done by means of four statistical measures including sensitivity, specificity, similarity index and Jaccard index. The average value of similarity index is 86.87%. The Jaccard index mean value is 83.85% which shows a good accuracy of segmentation. The average of sensitivity is 93.9% and mean value of the specificity is 89.45%. These results show the reliability of proposed method in these cases that manual segmentation is inapplicable. Huge shape variety of right-ventricle led us to use a shape prior based method and this work can develop by four-dimensional processing for determining the first ventricular slices.

Cardiac magnetic resonance imaging in heart failure: where the alphabet begins!

PubMed

Aljizeeri, Ahmed; Sulaiman, Abdulbaset; Alhulaimi, Naji; Alsaileek, Ahmed; Al-Mallah, Mouaz H

2017-07-01

Cardiac Magnetic Resonance Imaging has become a cornerstone in the evaluation of heart failure. It provides a comprehensive evaluation by answering all the pertinent clinical questions across the full pathological spectrum of heart failure. Nowadays, CMR is considered the gold standard in evaluation of ventricular volumes, wall motion and systolic function. Through its unique ability of tissue characterization, it provides incremental diagnostic and prognostic information and thus has emerged as a comprehensive imaging modality in heart failure. This review outlines the role of main conventional CMR sequences in the evaluation of heart failure and their impact in the management and prognosis.

LGE Provides Incremental Prognostic Information Over Serum Biomarkers in AL Cardiac Amyloidosis.

PubMed

Boynton, Samuel J; Geske, Jeffrey B; Dispenzieri, Angela; Syed, Imran S; Hanson, Theodore J; Grogan, Martha; Araoz, Philip A

2016-06-01

This study sought to determine the prognostic value of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in amyloid light chain (AL) cardiac amyloidosis. Cardiac involvement is the major determinant of mortality in AL amyloidosis. CMR LGE is a marker of amyloid infiltration of the myocardium. The purpose of this study was to evaluate retrospectively the prognostic value of CMR LGE for determining all-cause mortality in AL amyloidosis and to compare the prognostic power with the biomarker stage. Seventy-six patients with histologically proven AL amyloidosis underwent CMR LGE imaging. LGE was categorized as global, focal patchy, or none. Global LGE was considered present if it was visualized on LGE images or if the myocardium nulled before the blood pool on a cine multiple inversion time (TI) sequence. CMR morphologic and functional evaluation, echocardiographic diastolic evaluation, and cardiac biomarker staging were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. There were 40 deaths, and the median study follow-up period was 34.4 months. Global LGE was associated with all-cause mortality in univariate analysis (hazard ratio = 2.93; p < 0.001). In multivariate modeling with biomarker stage, global LGE remained prognostic (hazard ratio = 2.43; p = 0.01). Diffuse LGE provides incremental prognosis over cardiac biomarker stage in patients with AL cardiac amyloidosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Clinical use of cardiac PET/MRI: current state-of-the-art and potential future applications.

PubMed

Krumm, Patrick; Mangold, Stefanie; Gatidis, Sergios; Nikolaou, Konstantin; Nensa, Felix; Bamberg, Fabian; la Fougère, Christian

2018-05-01

Combined PET/MRI is a novel imaging method integrating the advances of functional and morphological MR imaging with PET applications that include assessment of myocardial viability, perfusion, metabolism of inflammatory tissue and tumors, as well as amyloid deposition imaging. As such, PET/MRI is a promising tool to detect and characterize ischemic and non-ischemic cardiomyopathies. To date, the greatest benefit may be expected for diagnostic evaluation of systemic diseases and cardiac masses that remain unclear in cardiac MRI, as well as for clinical and scientific studies in the setting of ischemic cardiomyopathies. Diagnosis and therapeutic monitoring of cardiac sarcoidosis has the potential of a possible 'killer-application' for combined cardiac PET/MRI. In this article, we review the current evidence and discuss current and potential future applications of cardiac PET/MRI.

Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure.

PubMed

Lataro, Renata M; Silva, Carlos A A; Fazan, Rubens; Rossi, Marcos A; Prado, Cibele M; Godinho, Rosely O; Salgado, Helio C

2013-10-15

Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. The parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling, and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4 wk of pyridostigmine administration, per os, methylatropine and propranolol were used to evaluate the cardiac sympathovagal balance. The tachycardic response caused by methylatropine was considered to be the vagal tone, whereas the bradycardic response caused by propranolol was considered to be the sympathetic tone. In conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output, and contractility of the left ventricle. It was demonstrated that the long-term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.

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.

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.

Structural and functional cardiac cholinergic deficits in adult neurturin knockout mice.

PubMed

Mabe, Abigail M; Hoover, Donald B

2009-04-01

Previous work provided indirect evidence that the neurotrophic factor neurturin (NRTN) is required for normal cholinergic innervation of the heart. This study used nrtn knockout (KO) and wild-type (WT) mice to determine the effect of nrtn deletion on cardiac cholinergic innervation and function in the adult heart. Immunohistochemistry, confocal microscopy, and quantitative image analysis were used to directly evaluate intrinsic cardiac neuronal development. Atrial acetylcholine (ACh) levels were determined as an indirect index of cholinergic innervation. Cholinergic function was evaluated by measuring negative chronotropic responses to right vagal nerve stimulation in anaesthetized mice and responses of isolated atria to muscarinic agonists. KO hearts contained only 35% the normal number of cholinergic neurons, and the residual cholinergic neurons were 15% smaller than in WT. Cholinergic nerve density at the sinoatrial node was reduced by 87% in KOs, but noradrenergic nerve density was unaffected. Atrial ACh levels were substantially lower in KO mice (0.013 +/- 0.004 vs. 0.050 +/- 0.011 pmol/microg protein; P < 0.02) as expected from cholinergic neuron and nerve fibre deficits. Maximum bradycardia evoked by vagal stimulation was reduced in KO mice (38 +/- 6% vs. 69 +/- 3% decrease at 20 Hz; P < 0.001), and chronotropic responses took longer to develop and fade. In contrast to these deficits, isolated atria from KO mice had normal post-junctional sensitivity to carbachol and bethanechol. These findings demonstrate that NRTN is essential for normal cardiac cholinergic innervation and cholinergic control of heart rate. The presence of residual cardiac cholinergic neurons and vagal bradycardia in KO mice suggests that additional neurotrophic factors may influence this system.

Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA-21 expression, Akt and the Bcl-2/Bax pathway

PubMed Central

Ma, Ning; Bai, Jingyun; Zhang, Weihua; Luo, Hong; Zhang, Xin; Liu, Donghai; Qiao, Chenhui

2016-01-01

Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)-21 expression, Akt, and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA-21, Bcl-2, Bax and phosphorylated-Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA-21 expression and phosphorylated-Akt protein expression, and reduced the Bcl-2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA-21 using anti-miR-21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA-21 serves a protective role in cardiac I/R injury via Akt and the Bcl-2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA-21 expression, Akt, and the Bcl-2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA-21 on cardiac I/R injury following treatment with trimetazidine in vivo. PMID:27666568

Follow-Up After Cardiac Surgery Should be Extended to at Least 120 Days When Benchmarking Cardiac Surgery Centers.

PubMed

Hansen, Laura S; Sloth, Erik; Hjortdal, Vibeke E; Jakobsen, Carl-Johan

2015-08-01

Short-term (30 days) mortality frequently is used as an outcome measure after cardiac surgery, although it has been proposed that the follow-up period should be extended to 120 days to allow for more accurate benchmarking. The authors aimed to evaluate whether mortality rates 120 days after surgery were comparable to general mortality and to compare causes of death between the cohort and the general population. A multicenter descriptive cohort study using prospectively entered registry data. University hospital. The cohort was obtained from the Western Denmark Heart Registry and matched to the Danish National Hospital Register as well as the Danish Register of Causes of Death. A weighted, age-matched general population consisting of all Danish patients who died within the study period was identified through the central authority on Danish statistics. A total of 11,988 patients (>15 years) who underwent cardiac-surgery at Aarhus, Aalborg and Odense University Hospitals from April 1, 2006 to December 31, 2012 were included. Coronary artery bypass grafting, valve surgery and combinations. Mortality after cardiac surgery matches with mortality in the general population after 140 days. Mortality curves run almost parallel from this point onwards, regardless of The European system for cardiac operative risk evaluation (EuroSCORE) and intervention. The causes of death in the cohort differed statistically significantly from the background population (p<0.0001; one-sample t-test) throughout the first postoperative year. The leading cause of death in the cohort was cardiac (38%); 53% of which was categorized as heart failure. A total of 54% of these patients were assessed preoperatively as having normal or mildly impaired heart function (EuroSCORE). This study supported an extended follow-up period after cardiac surgery when benchmarking cardiac surgery centers. Regardless of preoperative heart function, heart failure was the consistent leading cause of death. Copyright © 2015 Elsevier Inc. All rights reserved.

Gene Therapy With Angiotensin-(1-9) Preserves Left Ventricular Systolic Function After Myocardial Infarction.

PubMed

Fattah, Caroline; Nather, Katrin; McCarroll, Charlotte S; Hortigon-Vinagre, Maria P; Zamora, Victor; Flores-Munoz, Monica; McArthur, Lisa; Zentilin, Lorena; Giacca, Mauro; Touyz, Rhian M; Smith, Godfrey L; Loughrey, Christopher M; Nicklin, Stuart A

2016-12-20

Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin-angiotensin-aldosterone system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic mini-pump. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). The authors evaluated effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post-infarction. C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular pressure volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation/contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff-perfused whole-heart model. Gene delivery of Ang-(1-9) reduced sudden cardiac death post-MI. Pressure volume measurements revealed complete restoration of end-systolic pressure, ejection fraction, end-systolic volume, and the end-diastolic pressure volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. Our novel findings showed that Ang-(1-9) gene therapy preserved left ventricular systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) directly affected cardiomyocyte calcium handling through a protein kinase A-dependent mechanism. These data emphasized Ang-(1-9) gene therapy as a potential new strategy in the context of MI. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

In vivo imaging of the Drosophila Melanogaster heart using a novel optical coherence tomography microscope

NASA Astrophysics Data System (ADS)

Izatt, Susan D.; Choma, Michael A.; Israel, Steven; Wessells, Robert J.; Bodmer, Rolf; Izatt, Joseph A.

2005-03-01

Real time in vivo optical coherence tomography (OCT) imaging of the adult fruit fly Drosophila melanogaster heart using a newly designed OCT microscope allows accurate assessment of cardiac anatomy and function. D. melanogaster has been used extensively in genetic research for over a century, but in vivo evaluation of the heart has been limited by available imaging technology. The ability to assess phenotypic changes with micrometer-scale resolution noninvasively in genetic models such as D. melanogaster is needed in the advancing fields of developmental biology and genetics. We have developed a dedicated small animal OCT imaging system incorporating a state-of-the-art, real time OCT scanner integrated into a standard stereo zoom microscope which allows for simultaneous OCT and video imaging. System capabilities include A-scan, B-scan, and M-scan imaging as well as automated 3D volumetric acquisition and visualization. Transverse and sagittal B-mode scans of the four chambered D. melanogaster heart have been obtained with the OCT microscope and are consistent with detailed anatomical studies from the literature. Further analysis by M-mode scanning is currently under way to assess cardiac function as a function of age and sex by determination of shortening fraction and ejection fraction. These studies create control cardiac data on the wild type D. melanogaster, allowing subsequent evaluation of phenotypic cardiac changes in this model after regulated genetic mutation.

[Isolated left ventricular non-compaction associated with Ebstein's anomaly. Multimodality non-invasive imaging for the assessment of congenital heart disease].

PubMed

Renilla, Alfredo; Santamarta, Elena; Corros, Cecilia; Martín, María; Barreiro, Manuel; de la Hera, Jesús

2013-01-01

To establish the etiology of heart failure in patients with congenital heart disease can be challenging. Multiple concomitant anomalies that can be missed after an initial diagnosis could be seen in these patients. In patients with congenital heart disease, a more accurate evaluation of cardiac morphology and left ventricular systolic function could be evaluated by recent non-invasive cardiac imaging techniques. We present a rare case where multimodal cardiac imaging was useful to establish the final diagnosis of left ventricular non-compaction associated with Ebstein's anomaly. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

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.

Insulin-Like Growth Factor I (IGF-1) Deficiency Ameliorates Sex Difference in Cardiac Contractile Function and Intracellular Ca2+ Homeostasis

PubMed Central

Ceylan-Isik, Asli F.; Li, Qun; Ren, Jun

2011-01-01

Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR90), fura-fluorescence intensity (FFI) and intracellular Ca2+ clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ± dL/dt, longer TPS, TR90 and intracellular Ca2+ clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na+-Ca2+ exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca2+ regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca2+ regulation. PMID:21763763

Insulin-like growth factor I (IGF-1) deficiency ameliorates sex difference in cardiac contractile function and intracellular Ca(2+) homeostasis.

PubMed

Ceylan-Isik, Asli F; Li, Qun; Ren, Jun

2011-10-10

Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (±dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR(90)), fura-fluorescence intensity (FFI) and intracellular Ca(2+) clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ±dL/dt, longer TPS, TR(90) and intracellular Ca(2+) clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na(+)-Ca(2+) exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca(2+) regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca(2+) regulation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Influence of electronic apex locators and a gutta-percha heating device on implanted cardiac devices: an in vivo study.

PubMed

Moraes, A P; Silva, E J; Lamas, C C; Portugal, P H; Neves, A A

2016-06-01

To evaluate the potential for electromagnetic interference (EMI) of electronic apex locators (EALs) and a gutta-percha heating device (HD) in patients with implantable cardiac pacemakers (ICPs) or cardioverter-defibrillators (ICDs). Two types of EALs (Romiapex A-15 and Novapex) and a HD (Touch'n Heat) were tested in patients followed in an outpatient clinic for cardiac arrhythmias. The heart rhythm was monitored on a computer screen during all experimental phases. After baseline data collection, the patient held each appliance (turned on) for 30 s, simulating their clinical use. If background noise was detected on the cardiac monitor, the sensitivity of the ICP/ICD was lowered by the cardiologist to evaluate the intensity of the detected EMI. Twelve patients were evaluated (5 female and 7 male), and in nine instances, background noise in their cardiac devices related to the use of the endodontic devices was detected (6 patients). After lowering the sensitivity of the cardiac implants, three patients had more severe EMI in six instances, including pauses in ICP function. The presence of a symptomatic or asymptomatic pause was related to the patient's underlying heart rhythm. The HD device produced background noise more often compared to EALs. These were associated with more severe types of EMI. The EALs and gutta-percha HD were capable of causing background noise detection or pauses in cardiac implants in vivo. The use of electronic dental devices nearby patients with cardiac implants should be carefully considered in clinical practice. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

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.

Amalaki rasayana, a traditional Indian drug enhances cardiac mitochondrial and contractile functions and improves cardiac function in rats with hypertrophy.

PubMed

Kumar, Vikas; Aneesh, Kumar A; Kshemada, K; Ajith, Kumar G S; Binil, Raj S S; Deora, Neha; Sanjay, G; Jaleel, A; Muraleedharan, T S; Anandan, E M; Mony, R S; Valiathan, M S; Santhosh, Kumar T R; Kartha, C C

2017-08-17

We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated. Histology, gene and protein expression analysis were done in heart tissues. Chemical composition of AR was analyzed by HPLC, HPTLC and LC-MS. AR intake improved (P < 0.05) cardiac function in aging rats and decreased LVH (P < 0.05) in AC rats as well as increased (P < 0.05) fatigue time in treadmill exercise in both groups. In heart tissues of AR administered rats of both the groups, SERCA2, CaM, Myh11, antioxidant, autophagy, oxidative phosphorylation and TCA cycle proteins were up regulated. ADRB1/2 and pCREB expression were increased; pAMPK, NF-kB were decreased. AR has thus a beneficial effect on myocardial energetics, muscle contractile function and exercise tolerance capacity.

Assessment of left ventricular function using pulsed tissue Doppler imaging in healthy dogs and dogs with spontaneous mitral regurgitation.

PubMed

Teshima, Kenji; Asano, Kazushi; Sasaki, Yukie; Kato, Yuka; Kutara, Kenji; Edamura, Kazuya; Hasegawa, Atsuhiko; Tanaka, Shigeo

2005-12-01

Pulsed tissue Doppler imaging (pulsed TDI) has been demonstrated to be useful for the estimation of left ventricular (LV) systolic and diastolic functions in various human cardiac diseases. The objectives of this study were to investigate the relationship between pulsed TDI and LV function by using cardiac catheterization in healthy dogs and to evaluate the clinical usefulness of pulsed TDI in dogs with spontaneous mitral regurgitation (MR). The peak early diastolic velocity (E'), peak atrial systolic velocity (A'), and peak systolic velocity (S') were detectable in the velocity profiles of the mitral annulus in all the dogs. In the healthy dogs, S' and E' were correlated with LV peak +dP/dt and -dP/dt, respectively. E' was lower in dogs with MR than in dogs without cardiac diseases. E/E' in the MR dogs with decompensated heart failure was significantly increased in comparison with those with compensated heart failure. The sensitivity and specificity of the E/E' cutoff value of 13.0 for identifying decompensated heart failure were 80% and 83%, respectively. In addition, E/E' was significantly correlated with the ratio of left atrial to aortic diameter. These findings suggest that canine pulsed TDI can be applied clinically for estimation of cardiac function and detection of cardiac decompensation and left atrial volume overload in dogs with MR.

Functional cardiac magnetic resonance microscopy

NASA Astrophysics Data System (ADS)

Brau, Anja Christina Sophie

2003-07-01

The study of small animal models of human cardiovascular disease is critical to our understanding of the origin, progression, and treatment of this pervasive disease. Complete analysis of disease pathophysiology in these animal models requires measuring structural and functional changes at the level of the whole heart---a task for which an appropriate non-invasive imaging method is needed. The purpose of this work was thus to develop an imaging technique to support in vivo characterization of cardiac structure and function in rat and mouse models of cardiovascular disease. Whereas clinical cardiac magnetic resonance imaging (MRI) provides accurate assessment of the human heart, the extension of cardiac MRI from humans to rodents presents several formidable scaling challenges. Acquiring images of the mouse heart with organ definition and fluidity of contraction comparable to that achieved in humans requires an increase in spatial resolution by a factor of 3000 and an increase in temporal resolution by a factor of ten. No single technical innovation can meet the demanding imaging requirements imposed by the small animal. A functional cardiac magnetic resonance microscopy technique was developed by integrating improvements in physiological control, imaging hardware, biological synchronization of imaging, and pulse sequence design to achieve high-quality images of the murine heart with high spatial and temporal resolution. The specific methods and results from three different sets of imaging experiments are presented: (1) 2D functional imaging in the rat with spatial resolution of 175 mum2 x 1 mm and temporal resolution of 10 ms; (2) 3D functional imaging in the rat with spatial resolution of 100 mum 2 x 500 mum and temporal resolution of 30 ms; and (3) 2D functional imaging in the mouse with spatial resolution down to 100 mum2 x 1 mm and temporal resolution of 10 ms. The cardiac microscopy technique presented here represents a novel collection of technologies capable of acquiring routine high-quality images of murine cardiac structure and function with minimal artifacts and markedly higher spatial resolution compared to conventional techniques. This work is poised to serve a valuable role in the evaluation of cardiovascular disease and should find broad application in studies ranging from basic pathophysiology to drug discovery.

Bone marrow-derived human mesenchymal stem cells express cardiomyogenic proteins but do not exhibit functional cardiomyogenic differentiation potential.

PubMed

Siegel, Georg; Krause, Petra; Wöhrle, Stefanie; Nowak, Patrick; Ayturan, Miriam; Kluba, Torsten; Brehm, Bernhard R; Neumeister, Birgid; Köhler, David; Rosenberger, Peter; Just, Lothar; Northoff, Hinnak; Schäfer, Richard

2012-09-01

Despite their paracrine activites, cardiomyogenic differentiation of bone marrow (BM)-derived mesenchymal stem cells (MSCs) is thought to contribute to cardiac regeneration. To systematically evaluate the role of differentiation in MSC-mediated cardiac regeneration, the cardiomyogenic differentiation potential of human MSCs (hMSCs) and murine MSCs (mMSCs) was investigated in vitro and in vivo by inducing cardiomyogenic and noncardiomyogenic differentiation. Untreated hMSCs showed upregulation of cardiac tropopin I, cardiac actin, and myosin light chain mRNA and protein, and treatment of hMSCs with various cardiomyogenic differentiation media led to an enhanced expression of cardiomyogenic genes and proteins; however, no functional cardiomyogenic differentiation of hMSCs was observed. Moreover, co-culturing of hMSCs with cardiomyocytes derived from murine pluripotent cells (mcP19) or with murine fetal cardiomyocytes (mfCMCs) did not result in functional cardiomyogenic differentiation of hMSCs. Despite direct contact to beating mfCMCs, hMSCs could be effectively differentiated into cells of only the adipogenic and osteogenic lineage. After intramyocardial transplantation into a mouse model of myocardial infarction, Sca-1(+) mMSCs migrated to the infarcted area and survived at least 14 days but showed inconsistent evidence of functional cardiomyogenic differentiation. Neither in vitro treatment nor intramyocardial transplantation of MSCs reliably generated MSC-derived cardiomyocytes, indicating that functional cardiomyogenic differentiation of BM-derived MSCs is a rare event and, therefore, may not be the main contributor to cardiac regeneration.

Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction

PubMed Central

Russell, Richard O.; Rackley, Charles E.; Pombo, Jaoquin; Hunt, David; Potanin, Constantine; Dodge, Harold T.

1970-01-01

Left ventricular performance in 19 patients with acute myocardial infarction has been evaluated by measuring left ventricular response in terms of cardiac output, stroke volume, work, and power to progressive elevation of filling pressure accomplished by progressive expansion of blood volume with rapid infusion of low molecular weight dextran. Such infusion can elevate the cardiac output, stroke volume, work, and power and thus delineate the function of the left ventricle by Frank-Starling function curves. Left ventricular filling pressure in the range of 20-24 mm Hg was associated with the peak of the curves and when the filling pressure exceeded this range, the curves became flattened or decreased. An increase in cardiac output could be maintained for 4 or more hr. Patients with a flattened function curve had a high mortality in the ensuing 8 wk. The function curve showed improvement in myocardial function during the early convalescence. When left ventricular filling pressure is monitored directly or as pulmonary artery end-diastolic pressure, low molecular weight dextran provides a method for assessment of left ventricular function. Images PMID:5431663

Echocardiography in the Era of Multimodality Cardiovascular Imaging

PubMed Central

Shah, Benoy Nalin

2013-01-01

Echocardiography remains the most frequently performed cardiac imaging investigation and is an invaluable tool for detailed and accurate evaluation of cardiac structure and function. Echocardiography, nuclear cardiology, cardiac magnetic resonance imaging, and cardiovascular-computed tomography comprise the subspeciality of cardiovascular imaging, and these techniques are often used together for a multimodality, comprehensive assessment of a number of cardiac diseases. This paper provides the general cardiologist and physician with an overview of state-of-the-art modern echocardiography, summarising established indications as well as highlighting advances in stress echocardiography, three-dimensional echocardiography, deformation imaging, and contrast echocardiography. Strengths and limitations of echocardiography are discussed as well as the growing role of real-time three-dimensional echocardiography in the guidance of structural heart interventions in the cardiac catheter laboratory. PMID:23878804

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.

Does point-of-care functional echocardiography enhance cardiovascular care in the NICU?

PubMed

Sehgal, A; McNamara, P J

2008-11-01

Although the last two decades have seen major advances in the care of sick, extremely premature newborns, the approach to cardiovascular assessment and monitoring remains suboptimal owing to an overreliance on poorly predictive clinical markers such as heart rate or capillary refill time. Point-of-care functional echocardiography (PCFecho) enables real-time evaluation of cardiac performance and systemic hemodynamics to characterize acute physiology, identify the exact nature of cardiovascular compromise and guide therapeutic decisions. In this article, we will review four clinical scenarios where bedside functional cardiac imaging enabled delineation of the real clinical problem and refinement of the therapeutic care plan with direct patient benefits.

Calcitriol Prevents Cardiovascular Repercussions in Puromycin Aminonucleoside-Induced Nephrotic Syndrome

PubMed Central

Roberto, Roncon-Albuquerque

2018-01-01

Puromycin aminonucleoside-induced nephrotic syndrome (PAN-NS) is characterized by cardiac remodeling and increased local inflammatory activity. Patients with NS and animal models of NS have vitamin D3 deficiency. The aim of the present study was to evaluate the influence of calcitriol on cardiac remodeling and local inflammatory state in PAN-NS rat model. Male Sprague-Dawley rats were injected with PAN or vehicle on day 0. PAN and control rats were divided into two subgroups for the administration of calcitriol (PAN-D and Ct-D groups) or the vehicle (PAN-V and Ct-V groups) during 21 days. On day 21, the renal function, metabolic balance, calcitriol and FGF-23 plasma levels, prohypertrophy and proinflammatory markers (ET-1, TGF-β1, TNF-α, and IL-1β), and calcium signaling molecules (PLB and SERCA-2a) were evaluated. Twenty-one days after injection, PAN-V group presented cardiac hypertrophy and a modulation of proinflammatory markers local expression. Calcitriol treatment of PAN rats prevented cardiac hypertrophy and was associated with marked reduction in the cardiac expression levels of proinflammatory markers. Our results suggest that vitamin D3 deficiency in PAN-NS may contribute to cardiac remodeling and to the increase in local inflammatory activity. Calcitriol treatment prevents both cardiac repercussions and local inflammatory processes in PAN-NS. PMID:29607318

Post-conditioning preserves glycolytic ATP during early reperfusion: a survival mechanism for the reperfused heart.

PubMed

Correa, Francisco; García, Noemí; Gallardo-Pérez, Juan; Carreno-Fuentes, Liliana; Rodríguez-Enríquez, Sara; Marín-Hernández, Alvaro; Zazueta, Cecilia

2008-01-01

Glycolytic activity during the transition period from anaerobic to aerobic metabolism has been demonstrated to be critical for heart recovery in isolated reperfused hearts. The purpose of this work was to investigate the relevance of the glycolytic pathway in preserving the cardiac function of post-conditioned hearts. The activation of the glycolytic pathway in post-conditioned hearts was evaluated by measuring GLUT-4 insertion, glucose consumption and lactate production. Iodoacetic acid and 2-deoxy-D-glucose were administrated to the working hearts to evaluate the effect of glycolytic inhibition in the post-conditioning protective effect. Post-conditioning maneuvers applied to isolated rat hearts, after prolonged ischemia and before reperfusion, promoted recovery of cardiac mechanical function with sustained increase of GLUT-4 translocation and activation of the glycolytic pathway during ischemia and early reperfusion. Iodoacetate inhibited the protective effect of post-conditioning, without affecting the mitochondrial oxidative capacity. Glycolysis contribution to maintain mechanical function at early reperfusion was observed in post-conditioned hearts perfused with 2-deoxy-D-glucose and in hearts in which iodoacetate was administered only during reperfusion. It is concluded that in the post-conditioned heart, a functional compartmentation of anaerobic energy metabolism, at early reperfusion, plays a significant role in cardiac protection against reperfusion damage. Copyright 2008 S. Karger AG, Basel.

EPAC expression and function in cardiac fibroblasts and myofibroblasts

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

Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy

In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF weremore » treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac fibroblast. • PKA regulates collagen gel contraction in cardiac myofibroblast.« less

Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting

PubMed Central

Christiansen, Sofie Lindgren; Hertz, Christin Løth; Ferrero-Miliani, Laura; Dahl, Morten; Weeke, Peter Ejvin; LuCamp; Ottesen, Gyda Lolk; Frank-Hansen, Rune; Bundgaard, Henning; Morling, Niels

2016-01-01

In forensic medicine, one-third of the sudden deaths remain unexplained after medico-legal autopsy. A major proportion of these sudden unexplained deaths (SUD) are considered to be caused by inherited cardiac diseases. Sudden cardiac death (SCD) may be the first manifestation of these diseases. The purpose of this study was to explore the yield of next-generation sequencing of genes associated with SCD in a cohort of SUD victims. We investigated 100 genes associated with cardiac diseases in 61 young (1–50 years) SUD cases. DNA was captured with the Haloplex target enrichment system and sequenced using an Illumina MiSeq. The identified genetic variants were evaluated and classified as likely, unknown or unlikely to have a functional effect. The criteria for this classification were based on the literature, databases, conservation and prediction of the effect of the variant. We found that 21 (34%) individuals carried variants with a likely functional effect. Ten (40%) of these variants were located in genes associated with cardiomyopathies and 15 (60%) of the variants in genes associated with cardiac channelopathies. Nineteen individuals carried variants with unknown functional effect. Our findings indicate that broad genetic investigation of SUD victims increases the diagnostic outcome, and the investigation should comprise genes involved in both cardiomyopathies and cardiac channelopathies. PMID:27650965

Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting.

PubMed

Christiansen, Sofie Lindgren; Hertz, Christin Løth; Ferrero-Miliani, Laura; Dahl, Morten; Weeke, Peter Ejvin; LuCamp; Ottesen, Gyda Lolk; Frank-Hansen, Rune; Bundgaard, Henning; Morling, Niels

2016-12-01

In forensic medicine, one-third of the sudden deaths remain unexplained after medico-legal autopsy. A major proportion of these sudden unexplained deaths (SUD) are considered to be caused by inherited cardiac diseases. Sudden cardiac death (SCD) may be the first manifestation of these diseases. The purpose of this study was to explore the yield of next-generation sequencing of genes associated with SCD in a cohort of SUD victims. We investigated 100 genes associated with cardiac diseases in 61 young (1-50 years) SUD cases. DNA was captured with the Haloplex target enrichment system and sequenced using an Illumina MiSeq. The identified genetic variants were evaluated and classified as likely, unknown or unlikely to have a functional effect. The criteria for this classification were based on the literature, databases, conservation and prediction of the effect of the variant. We found that 21 (34%) individuals carried variants with a likely functional effect. Ten (40%) of these variants were located in genes associated with cardiomyopathies and 15 (60%) of the variants in genes associated with cardiac channelopathies. Nineteen individuals carried variants with unknown functional effect. Our findings indicate that broad genetic investigation of SUD victims increases the diagnostic outcome, and the investigation should comprise genes involved in both cardiomyopathies and cardiac channelopathies.

[Cardiac Synchronization Function Estimation Based on ASM Level Set Segmentation Method].

PubMed

Zhang, Yaonan; Gao, Yuan; Tang, Liang; He, Ying; Zhang, Huie

At present, there is no accurate and quantitative methods for the determination of cardiac mechanical synchronism, and quantitative determination of the synchronization function of the four cardiac cavities with medical images has a great clinical value. This paper uses the whole heart ultrasound image sequence, and segments the left & right atriums and left & right ventricles of each frame. After the segmentation, the number of pixels in each cavity and in each frame is recorded, and the areas of the four cavities of the image sequence are therefore obtained. The area change curves of the four cavities are further extracted, and the synchronous information of the four cavities is obtained. Because of the low SNR of Ultrasound images, the boundary lines of cardiac cavities are vague, so the extraction of cardiac contours is still a challenging problem. Therefore, the ASM model information is added to the traditional level set method to force the curve evolution process. According to the experimental results, the improved method improves the accuracy of the segmentation. Furthermore, based on the ventricular segmentation, the right and left ventricular systolic functions are evaluated, mainly according to the area changes. The synchronization of the four cavities of the heart is estimated based on the area changes and the volume changes.

Engineering a functional three-dimensional human cardiac tissue model for drug toxicity screening.

PubMed

Lu, Hong Fang; Leong, Meng Fatt; Lim, Tze Chiun; Chua, Ying Ping; Lim, Jia Kai; Du, Chan; Wan, Andrew C A

2017-05-11

Cardiotoxicity is one of the major reasons for clinical drug attrition. In vitro tissue models that can provide efficient and accurate drug toxicity screening are highly desired for preclinical drug development and personalized therapy. Here, we report the fabrication and characterization of a human cardiac tissue model for high throughput drug toxicity studies. Cardiac tissues were fabricated via cellular self-assembly of human transgene-free induced pluripotent stem cells-derived cardiomyocytes in pre-fabricated polydimethylsiloxane molds. The formed tissue constructs expressed cardiomyocyte-specific proteins, exhibited robust production of extracellular matrix components such as laminin, collagen and fibronectin, aligned sarcomeric organization, and stable spontaneous contractions for up to 2 months. Functional characterization revealed that the cardiac cells cultured in 3D tissues exhibited higher contraction speed and rate, and displayed a significantly different drug response compared to cells cultured in age-matched 2D monolayer. A panel of clinically relevant compounds including antibiotic, antidiabetic and anticancer drugs were tested in this study. Compared to conventional viability assays, our functional contractility-based assays were more sensitive in predicting drug-induced cardiotoxic effects, demonstrating good concordance with clinical observations. Thus, our 3D cardiac tissue model shows great potential to be used for early safety evaluation in drug development and drug efficiency testing for personalized therapy.

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.

Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

PubMed

Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

2015-01-01

Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

2017 Multimodality Appropriate Use Criteria for Noninvasive Cardiac Imaging: Expert Consensus of the Asian Society of Cardiovascular Imaging.

PubMed

Beck, Kyongmin Sarah; Kim, Jeong A; Choe, Yeon Hyeon; Hian, Sim Kui; Hoe, John; Hong, Yoo Jin; Kim, Sung Mok; Kim, Tae Hoon; Kim, Young Jin; Kim, Yun Hyeon; Kuribayashi, Sachio; Lee, Jongmin; Leong, Lilian; Lim, Tae-Hwan; Lu, Bin; Park, Jae Hyung; Sakuma, Hajime; Yang, Dong Hyun; Yaw, Tan Swee; Wan, Yung-Liang; Zhang, Zhaoqi; Zhao, Shihua; Yong, Hwan Seok

2017-01-01

In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1-9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making.

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.

Human auditory evoked potentials in the assessment of brain function during major cardiovascular surgery.

PubMed

Rodriguez, Rosendo A

2004-06-01

Focal neurologic and intellectual deficits or memory problems are relatively frequent after cardiac surgery. These complications have been associated with cerebral hypoperfusion, embolization, and inflammation that occur during or after surgery. Auditory evoked potentials, a neurophysiologic technique that evaluates the function of neural structures from the auditory nerve to the cortex, provide useful information about the functional status of the brain during major cardiovascular procedures. Skepticism regarding the presence of artifacts or difficulty in their interpretation has outweighed considerations of its potential utility and noninvasiveness. This paper reviews the evidence of their potential applications in several aspects of the management of cardiac surgery patients. The sensitivity of auditory evoked potentials to the effects of changes in brain temperature makes them useful for monitoring cerebral hypothermia and rewarming during cardiopulmonary bypass. The close relationship between evoked potential waveforms and specific anatomic structures facilitates the assessment of the functional integrity of the central nervous system in cardiac surgery patients. This feature may also be relevant in the management of critical patients under sedation and coma or in the evaluation of their prognosis during critical care. Their objectivity, reproducibility, and relative insensitivity to learning effects make auditory evoked potentials attractive for the cognitive assessment of cardiac surgery patients. From a clinical perspective, auditory evoked potentials represent an additional window for the study of underlying cerebral processes in healthy and diseased patients. From a research standpoint, this technology offers opportunities for a better understanding of the particular cerebral deficits associated with patients who are undergoing major cardiovascular procedures.

Preclinical in vivo long-term evaluation of the novel Mitra-Spacer technology: experimental validation in the ovine model.

PubMed

Peppas, Athanasios; Furer, Ariel; Wilson, Jon; Yi, GengHua; Cheng, Yanping; Van Wygerden, Karl; Seguin, Christopher; Shibuya, Masahiko; Kaluza, Grzegorz L; Granada, Juan F

2017-06-20

The Mitra-Spacer (Cardiosolutions, Bridgewater, MA, USA) is designed to treat mitral regurgitation by introducing a dynamic spacer that constantly adapts to the changing haemodynamic conditions during the cardiac cycle. We aimed to evaluate the performance and safety of this device in the chronic ovine model. Eight sheep were enrolled in this study. Through a left thoracotomy, the Mitra-Spacer was inserted via the transapical approach and advanced into the left atrium (LA) under imaging guidance. Device performance and safety were evaluated up to 90 days using fluoroscopy, echocardiography and histopathology. The volume within the balloon spacer shifted during the cardiac cycle in all cases. Seven animals survived up to 90 days for terminal imaging and tissue harvest. Echocardiography showed no change in left ventricle (LV) ejection fraction from baseline to 90 days. There were no observations of changes in LV diastolic function, pulmonary vein inflow, or tricuspid valve function. Histological analysis demonstrated no significant injury to the mitral apparatus. In the healthy ovine model, Mitra-Spacer implantation was feasible and safe. At 90 days, no evidence of structural damage to the mitral apparatus or deterioration of cardiac performance was demonstrated.

Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy.

PubMed

Heikal, N M; Bader, F M; Martins, T B; Pavlov, I Y; Wilson, A R; Barakat, M; Stehlik, J; Kfoury, A G; Gilbert, E M; Delgado, J C; Hill, H R

2013-01-01

Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001). Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies. Published by Elsevier Inc.

[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.

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.

Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.

PubMed

Zhang, Shouxin; Liu, Xiaoyan; Sun, Chengming; Yang, Jun; Wang, Lihong; Liu, Jie; Gong, Lei; Jing, Yanyan

2016-04-01

This study aims to investigate the protective effect of apigenin on the development of experimental autoimmune myocarditis (EAM) and the underlying mechanisms. An EAM model was induced in BALB/c mice by the injection of porcine cardiac myosin. Apigenin was orally administered from day 1 to 21. The severity of myocarditis was assessed by determination of heart weight/body weight ratio (HW/BW) and histopathological evaluation. Echocardiography was conducted to evaluate the cardiac function and heart structure. Antigen-specific T cell proliferation responses to cardiac myosin were evaluated by the lymphocyte proliferation assay. ELISA was used to determine serum levels of type 1 helper (Th1) and Th2 cytokines. Apigenin treatment significantly decreased HW/BW. Histopathologic analysis showed that the infiltration of inflammatory cells was reduced significantly by apigenin treatment. Meanwhile, apigenin administration effectively ameliorated autoimmune myocarditis-induced cardiac hypertrophy and cardiac dysfunction as well as inhibited lymphocyte proliferation in mice immunized with myosin. Furthermore, Th1 cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) were significantly downregulated, while Th2 cytokines IL-4 and IL-10 were markedly upregulated. The results indicated that apigenin can alleviate EAM due to its immunomodulatory reactions in modification of helper T cell balance.

Kinetics of Mechanical Stretch-Induced Nitric Oxide Production in Rat Ventricular Cardiac Myocytes.

PubMed

Shim, A L; Mitrokhin, V M; Gorbacheva, L R; Savinkova, I G; Pustovit, K B; Mladenov, M I; Kamkin, A G

2017-09-01

Discrete mechanical stretch of isolated spontaneously contracting cardiac myocytes was employed to examine the kinetics of NO production in these cells. NO oscillations were detected with fluorescent dye 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate. The mechanisms underlying stretch-induced changes in NO concentration remain unclear and further studies are needed to evaluate the role of NO oscillation in the regulation of cardiomyocyte function.

Functional expression and pharmaceutical efficacy of cardiac-specific ion channels in human embryonic stem cell-derived cardiomyocytes.

PubMed

Kim, Han Sol; Yoon, Jung Won; Li, Hongliang; Jeong, Geun Ok; Park, Jin Ju; Shin, Sung Eun; Jang, Il Ho; Kim, Jae Ho; Park, Won Sun

2017-10-23

Cardiomyocytes differentiated from human pluripotent stem cells provide promising tools for screening of cardiotoxic drugs. For evaluation of human pluripotent stem cell-derived cardiomyocytes for cardiotoxicity test, in the present study, human embryonic stem cells (hESCs) were differentiated to cardiomyocytes, followed by metabolic selection to enrich the differentiated cardiomyocytes. The highly purified hESC-derived cardiomyocytes (hESC-CMs) expressed several cardiomyocyte-specific markers including cTnT, MLC2a, and α-SA, but not pluripotency markers, such as OCT4 and NANOG. Patch clamp technique and RT-PCR revealed the expression of cardiomyocyte-specific Na + , Ca 2+ , and K + channels and cardiac action potential in hESC-CMs. To explore the potential use of hESC-CMs as functional cardiomyocytes for drug discovery and cardiotoxicity screening, we examined the effects of bisindolylmaleimide (BIM) (I), which inhibits native cardiac Ca 2+ channels, on the Ca 2+ channel activity of hESC-CMs. We observed a similar response for the BIM (I)-induced modulation of Ca 2+ channels between hESC-CMs and native cardiomyocytes through L-type Ca 2+ channel current. These results suggest that hESC-CMs can be useful for evaluation of pharmaceutical efficacy and safety of novel drug candidate in cardiac research.

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.

Fetal tissue Doppler imaging in pregnancies complicated with preeclampsia with or without intrauterine growth restriction.

PubMed

Zhou, Qiongjie; Ren, Yunyun; Yan, Yingliu; Chu, Chen; Gui, Yonghao; Li, Xiaotian

2012-11-01

This study's aim was to evaluate the effect of preeclampsia and intrauterine growth restriction (IUGR) on fetal cardiac function, and the relationship of the latter with adverse pregnancy outcomes. We did a cross-sectional study of 132 women with uncomplicated singleton pregnancies, 34 with preeclampsia without IUGR, and 12 with preeclampsia and IUGR. Fetal cardiac structure and function were evaluated using fetal two-dimension ultrasound, pulsed wave Doppler and tissue Doppler imaging (TDI). Data were analyzed by t-tests, ANOVA, Chi-square tests, or Wilcoxon rank-sum test. Compared with the normal pregnancy group, mitral/tricuspid early systolic peak velocity of annulus/late diastolic peak velocity of annulus (Sa) and left ventricular (LV)/right ventricular (RV) early diastolic peak velocity at the annulus (Ea) in TDI decreased in preeclampsia with or without IUGR (P < 0.05). LV/RV Ea underwent a gestational decrease in preeclampsia with or without IUGR (P < 0.05). The changes in mitral/tricuspid Sa and LV Sa associated with preeclampsia were even more pronounced with preterm delivery at less than 34 gestational weeks and stillbirth (P < 0.05). Intrauterine growth restriction influences fetal cardiac function in the presence of preeclampsia, and TDI may be a sensitive and preferable method to detect such changes. Fetal LV/RV Ea is a potential marker for early fetal cardiac diastolic impairment, and mitral/tricuspid Sa and LV Sa may be predictors for adverse pregnancy outcomes. © 2012 John Wiley & Sons, Ltd.

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy.

PubMed

Raimundo, Joyce R S; Bergamaschi, Cassia T; Campos, Ruy R; Palma, Beatriz D; Tufik, Sergio; Gomes, Guiomar N

2016-09-01

Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

Regenerating Heart Using a Novel Compound and Human Wharton Jelly Mesenchymal Stem Cells.

PubMed

Rabbani, Shahram; Soleimani, Masoud; Imani, Mohammad; Sahebjam, Mohammad; Ghiaseddin, Ali; Nassiri, Seyed Mahdi; Majd Ardakani, Jalil; Tajik Rostami, Maryam; Jalali, Arash; Mousanassab, Bahmanshir; Kheradmandi, Mahsa; Ahmadi Tafti, Seyed Hossein

2017-04-01

Myocardial infarction is a major problem in health system and most conventional therapy is not led to restoration of the health. Stem cell therapy is a method to regenerate the heart but today appropriate cell source and scaffold selection as extracellular matrix to achieve the best effect is disputing. In this study a combination of human Wharton jelly mesenchymal stem cells (HWJMSCs) with a novel compound consisting polyethylene glycol (PEG), hyaluronic acid and chitosan is presented to heart regeneration. After proliferation and expansion of HWJMSCs, these cells were mixed with scaffold and injected into the infarcted rabbit myocardium. After two months cardiac function and infarcted area were evaluated. Immunohistochemistry performed for vessel count and demonstrating of differentiation ability into cardiomyocytes. To confirm this ability PCR was done. Scanning electron microscope was used to evaluate angiogenesis. Improving cardiac function was higher in cell/scaffold group than the others and it was confirmed by SPECT results which showed least defect size in the myocardium. There were a lot of neoangiogenesis in the target group and also cardiomyogenesis observed in cell/scaffold group. PCR results confirmed the presence of differentiated cardiomyocytes and SEM showed well developed vessel in this group. Comparing macroscopic and microscopic results between all groups revealed that HWJMSC in combination with this scaffold led to brilliant results regarding cardiac function, angiogenesis and cardiogenesis. It is recommended using these cells and materials for cardiac tissue engineering and regeneration therapy. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

Sex differences in cardiac function after prolonged strenuous exercise.

PubMed

Cote, Anita T; Phillips, Aaron A; Foulds, Heather J; Charlesworth, Sarah A; Bredin, Shannon S D; Burr, Jamie F; Koehle, Michael S; Warburton, Darren E R

2015-05-01

To evaluate sex differences in left ventricular (LV) function after an ultramarathon, and the association of vascular and training indices with the magnitude of exercise-induced cardiac fatigue. Descriptive field study. Fat Dog 100 Ultramarathon Trail Race, Canada. Thirty-four (13 women) recreational runners (aged 28-56 years). A 100-km or 160-km mountain marathon. Baseline baroreceptor sensitivity, heart rate variability, and arterial compliance; Pre-exercise and postexercise echocardiographic evaluations of LV dimensions, volumes, Doppler flow velocities, tissue velocities, strain, and strain rate. Finishers represented 17 men (44.8 ± 6.6 years) and 8 women (45.9 ± 10.2 years; P = 0.758). After ultraendurance exercise, significant reductions (P < 0.05) in fractional shortening (men: 40.9 ± 6.9 to 34.1 ± 7.6%; women: 42.5 ± 6.5 to 34.6 ± 7.9%) diastolic filling (E/A, men: 1.28 ± 0.68 to 1.26 ± 0.33; women: 1.55 ± 0.51 to 1.30 ± 0.27), septal and lateral tissue velocities (E'), and longitudinal strain (men: -21.02 ± 1.98 to -18.44 ± 0.34; women: -20.28 ± 1.90 to -18.44 ± 2.34) were observed. Sex differences were found for baseline cardiac structure and global function, peak late transmitral flow velocity, and estimates of LV filling pressures (P < 0.05). Regression analysis found that higher baseline arterial compliance was associated with lower reductions in cardiac function postexercise, to which sex was a significant factor for E' of the lateral wall. Faster race pace and greater lifetime ultramarathons were associated with lower reductions in LV longitudinal strain (P < 0.05). Cardiac responses after an ultramarathon were similar between men and women. Greater evidence of exercise-induced cardiac fatigue was found to be associated with lower baseline arterial compliance and training status/experience. These findings suggest that vascular health is an important contributor to the degree of cardiovascular strain incurred as the result of an acute bout of prolonged strenuous exercise.

Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

PubMed

Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

2015-10-01

Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

Left atrial function: evaluation by strain analysis

PubMed Central

Gan, Gary C. H.; Ferkh, Aaisha; Boyd, Anita

2018-01-01

The left atrium has an important role in modulating left ventricular filling and is an important biomarker of cardiovascular disease and adverse cardiovascular outcomes. While previously left atrial (LA) size was utilised, the role of LA function as a biomarker is increasingly being evaluated, both independently and also in combination with LA size. Strain analysis has been utilised for evaluation of LA function and can be measured throughout the cardiac cycle, thereby enabling the evaluation of LA reservoir, conduit and contractile function. Strain evaluates myocardial deformation while strain rate examines the rate of change in strain. This review will focus on the various types of strain analysis for evaluation of LA function, alterations in LA strain in physiological and pathologic states that alter LA function and finally evaluate its utility as a prognostic marker. PMID:29541609

Detraining Differentially Preserved Beneficial Effects of Exercise on Hypertension: Effects on Blood Pressure, Cardiac Function, Brain Inflammatory Cytokines and Oxidative Stress

PubMed Central

Agarwal, Deepmala; Dange, Rahul B.; Vila, Jorge; Otamendi, Arturo J.; Francis, Joseph

2012-01-01

Aims This study sought to investigate the effects of physical detraining on blood pressure (BP) and cardiac morphology and function in hypertension, and on pro- and anti-inflammatory cytokines (PICs and AIC) and oxidative stress within the brain of hypertensive rats. Methods and Results Hypertension was induced in male Sprague-Dawley rats by delivering AngiotensinII for 42 days using implanted osmotic minipumps. Rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise (ExT) for 42 days, whereas, detrained groups underwent 28 days of exercise followed by 14 days of detraining. BP and cardiac function were evaluated by radio-telemetry and echocardiography, respectively. At the end, the paraventricular nucleus (PVN) was analyzed by Real-time RT-PCR and Western blot. ExT in AngII-infused rats caused delayed progression of hypertension, reduced cardiac hypertrophy, and improved diastolic function. These results were associated with significantly reduced PICs, increased AIC (interleukin (IL)-10), and attenuated oxidative stress in the PVN. Detraining did not abolish the exercise-induced attenuation in MAP in hypertensive rats; however, detraining failed to completely preserve exercise-mediated improvement in cardiac hypertrophy and function. Additionally, detraining did not reverse exercise-induced improvement in PICs in the PVN of hypertensive rats; however, the improvements in IL-10 were abolished. Conclusion These results indicate that although 2 weeks of detraining is not long enough to completely abolish the beneficial effects of regular exercise, continuing cessation of exercise may lead to detrimental effects. PMID:23285093

Cortistatin Improves Cardiac Function After Acute Myocardial Infarction in Rats by Suppressing Myocardial Apoptosis and Endoplasmic Reticulum Stress.

PubMed

Shi, Zhi-Yu; Liu, Yue; Dong, Li; Zhang, Bo; Zhao, Meng; Liu, Wen-Xiu; Zhang, Xin; Yin, Xin-Hua

2016-04-18

The endoplasmic reticulum (ER) stress-induced apoptotic pathway is associated with the development of acute myocardial infarction (AMI). Cortistatin (CST) is a novel bioactive peptide that inhibits apoptosis-related injury. Therefore, we investigated the cardioprotective effects and potential mechanisms of CST in a rat model of AMI. Male Wistar rats were randomly divided into sham, AMI, and AMI + CST groups. Cardiac function and the degree of infarction were evaluated by echocardiography, cardiac troponin I activity, and 2,3,5-triphenyl-2H-tetrazolium chloride staining after 7 days. The expression of CST, ER stress markers, and apoptotic markers was examined using immunohistochemistry and Western blotting. Compared to the AMI group, the AMI + CST group exhibited markedly better cardiac function and a lower degree of infarction. Electron microscopy and terminal deoxynucleotidyl transferase dUTP nick end labeling confirmed that myocardial apoptosis occurred after AMI. Cortistatin treatment reduced the expression of caspase 3, cleaved caspase 3, and Bax (proapoptotic proteins) and promoted the expression of Bcl-2 (antiapoptotic protein). In addition, the reduced expression of glucose-regulated protein 94 (GRP94), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding proteins homologous protein, and caspase 12 indicated that ER stress and the apoptotic pathway associated with ER stress were suppressed. Exogenous CST has a notable cardioprotective effect after AMI in a rat model in that it improves cardiac function by suppressing ER stress and myocardial apoptosis. © The Author(s) 2016.

Automatic right ventricle (RV) segmentation by propagating a basal spatio-temporal characterization

NASA Astrophysics Data System (ADS)

Atehortúa, Angélica; Zuluaga, María. A.; Martínez, Fabio; Romero, Eduardo

2015-12-01

An accurate right ventricular (RV) function quantification is important to support the evaluation, diagnosis and prognosis of several cardiac pathologies and to complement the left ventricular function assessment. However, expert RV delineation is a time consuming task with high inter-and-intra observer variability. In this paper we present an automatic segmentation method of the RV in MR-cardiac sequences. Unlike atlas or multi-atlas methods, this approach estimates the RV using exclusively information from the sequence itself. For so doing, a spatio-temporal analysis segments the heart at the basal slice, segmentation that is then propagated to the apex by using a non-rigid-registration strategy. The proposed approach achieves an average Dice Score of 0:79 evaluated with a set of 48 patients.

Hypophosphatemia-induced Cardiomyopathy.

PubMed

Ariyoshi, Nobuhiro; Nogi, Masayuki; Ando, Akika; Watanabe, Hideaki; Umekawa, Sari

2016-09-01

Relatively few studies have been conducted to evaluate the effect of hypophosphatemia on cardiac function. The goal of this review was to determine whether there is an association between hypophosphatemia and cardiac function and to increase awareness of hypophosphatemia-induced cardiomyopathy as a new clinical entity and a reversible cause of heart failure. We searched MEDLINE and PubMed from 1971 until March 2015 for primary studies, which reported the relationship between hypophosphatemia and cardiac function. A total of 837 articles were initially obtained. Of these articles, 826 publications were excluded according to the inclusion and exclusion criteria. In all, 11 articles were included in this review. These articles included 7 case series or case reports, 1 case-control study, 1 pretest versus posttest in a single group and 2 animal studies. In conclusion, the mechanisms of hypophosphatemia in cardiomyopathy have been reported to be a depletion of adenosine triphosphate in myocardial cells and decreased 2,3-diphosphoglycerate in erythrocytes. After correction of hypophosphatemia, left ventricular performance seems to improve in patients with severe hypophosphatemia, but not in those with mild-to-moderate hypophosphatemia. However, analyses of the relationship between cardiac function and hypophosphatemia using clinical end points have not been conducted. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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.

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

PubMed

Moler, Frank W; Silverstein, Faye S; Holubkov, Richard; Slomine, Beth S; Christensen, James R; Nadkarni, Vinay M; Meert, Kathleen L; Clark, Amy E; Browning, Brittan; Pemberton, Victoria L; Page, Kent; Shankaran, Seetha; Hutchison, Jamie S; Newth, Christopher J L; Bennett, Kimberly S; Berger, John T; Topjian, Alexis; Pineda, Jose A; Koch, Joshua D; Schleien, Charles L; Dalton, Heidi J; Ofori-Amanfo, George; Goodman, Denise M; Fink, Ericka L; McQuillen, Patrick; Zimmerman, Jerry J; Thomas, Neal J; van der Jagt, Elise W; Porter, Melissa B; Meyer, Michael T; Harrison, Rick; Pham, Nga; Schwarz, Adam J; Nowak, Jeffrey E; Alten, Jeffrey; Wheeler, Derek S; Bhalala, Utpal S; Lidsky, Karen; Lloyd, Eric; Mathur, Mudit; Shah, Samir; Wu, Theodore; Theodorou, Andreas A; Sanders, Ronald C; Dean, J Michael

2015-05-14

Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

ASCI 2010 appropriateness criteria for cardiac computed tomography: a report of the Asian Society of Cardiovascular Imaging Cardiac Computed Tomography and Cardiac Magnetic Resonance Imaging Guideline Working Group.

PubMed

Tsai, I-Chen; Choi, Byoung Wook; Chan, Carmen; Jinzaki, Masahiro; Kitagawa, Kakuya; Yong, Hwan Seok; Yu, Wei

2010-02-01

In Asia, the healthcare system, populations and patterns of disease differ from Western countries. The current reports on the criteria for cardiac CT scans, provided by Western professional societies, are not appropriate for Asian cultures. The Asian Society of Cardiovascular Imaging, the only society dedicated to cardiovascular imaging in Asia, formed a Working Group and invited 23 Technical Panel members representing a variety of Asian countries to rate the 51 indications for cardiac CT in clinical practice in Asia. The indications were rated as 'appropriate' (7-9), 'uncertain' (4-6), or 'inappropriate' (1-3) on a scale of 1-9. The median score was used for the final result if there was no disagreement. The final ratings for indications were 33 appropriate, 14 uncertain and 4 inappropriate. And 20 of them are highly agreed (19 appropriate and 1 inappropriate). Specifically, the Asian representatives considered cardiac CT as an appropriate modality for Kawasaki disease and congenital heart diseases in follow up and in symptomatic patients. In addition, except for some specified conditions, cardiac CT was considered to be an appropriate modality for one-stop shop ischemic heart disease evaluation due to its general appropriateness in coronary, structure and function evaluation. This report is expected to have a significant impact on the clinical practice, research and reimbursement policy in Asia.

Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus.

PubMed

Gonçalves, N; Gomes-Ferreira, C; Moura, C; Roncon-Albuquerque, R; Leite-Moreira, A F; Falcão-Pires, I

2016-08-15

Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload. Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5weeks of DM the cardiac function and structure were evaluated. Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle. Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.

PubMed

Hamon, David; Rajendran, Pradeep S; Chui, Ray W; Ajijola, Olujimi A; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

2017-04-01

Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli ( P <0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response ( P <0.05 versus short CI), particularly on convergent neurons ( P <0.05), as well as neurons receiving sympathetic ( P <0.05) and parasympathetic input ( P <0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. © 2017 American Heart Association, Inc.

Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study.

PubMed

Weaver, Anne M; Wellenius, Gregory A; Wu, Wen-Chih; Hickson, DeMarc A; Kamalesh, Masoor; Wang, Yi

2016-06-13

Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150-299 m, 1161 lived 300-999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans.

2017 Multimodality Appropriate Use Criteria for Noninvasive Cardiac Imaging: Expert Consensus of the Asian Society of Cardiovascular Imaging

PubMed Central

Beck, Kyongmin Sarah; Kim, Jeong A; Choe, Yeon Hyeon; Hian, Sim Kui; Hoe, John; Hong, Yoo Jin; Kim, Sung Mok; Kim, Tae Hoon; Kim, Young Jin; Kim, Yun Hyeon; Kuribayashi, Sachio; Lee, Jongmin; Leong, Lilian; Lim, Tae-Hwan; Lu, Bin; Park, Jae Hyung; Sakuma, Hajime; Yang, Dong Hyun; Yaw, Tan Swee; Wan, Yung-Liang; Zhang, Zhaoqi; Zhao, Shihua

2017-01-01

In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1–9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making. PMID:29089819

Re-entry using anatomically determined isthmuses: a curable ventricular tachycardia in repaired congenital heart disease.

PubMed

Kapel, Gijsbert F L; Reichlin, Tobias; Wijnmaalen, Adrianus P; Piers, Sebastiaan R D; Holman, Eduard R; Tedrow, Usha B; Schalij, Martin J; Stevenson, William G; Zeppenfeld, Katja

2015-02-01

Ventricular tachycardia (VT) is an important cause of late morbidity and mortality in repaired congenital heart disease. The substrate often includes anatomic isthmuses that can be transected by radiofrequency catheter ablation similar to isthmus block for atrial flutter. This study evaluates the long-term efficacy of isthmus block for treatment of re-entry VT in adults with repaired congenital heart disease. Thirty-four patients (49±13 years; 74% male) with repaired congenital heart disease who underwent radiofrequency catheter ablation of VT in 2 centers were included. Twenty-two (65%) had a preserved left and right ventricular function. Patients were inducible for 1 (interquartile range, 1-2) VT, median cycle length: 295 ms (interquartile range, 242-346). Ablation aimed to transect anatomic isthmuses containing VT re-entry circuit isthmuses. Procedural success was defined as noninducibility of any VT and transection of the anatomic isthmus and was achieved in 25 (74%) patients. During long-term follow-up (46±29 months), all patients with procedural success (18/25 with internal cardiac defibrillators) were free of VT recurrence but 7 of 18 experienced internal cardiac defibrillator-related complications. One patient with procedural success and depressed cardiac function received an internal cardiac defibrillator shock for ventricular fibrillation. None of the 18 patients (12/18 with internal cardiac defibrillators) with complete success and preserved cardiac function experienced any ventricular arrhythmia. In contrast, VT recurred in 4 of 9 patients without procedural success. Four patients died from nonarrhythmic causes. In patients with repaired congenital heart disease with preserved ventricular function and isthmus-dependent re-entry, VT isthmus ablation can be curative. © 2014 American Heart Association, Inc.

Intermedin improves cardiac function and sympathetic neural remodeling in a rat model of post myocardial infarction heart failure

PubMed Central

Xu, Bin; Xu, Hao; Cao, Heng; Liu, Xiaoxiao; Qin, Chunhuan; Zhao, Yanzhou; Han, Xiaolin; Li, Hongli

2017-01-01

Emerging evidence has suggested that intermedin (IMD), a novel member of the calcitonin gene-related peptide (CGRP) family, has a wide range of cardioprotective effects. The present study investigated the effects of long-term administration of IMD on cardiac function and sympathetic neural remodeling in heart failure (HF) rats, and studied potential underlying mechanism. HF was induced in rats by myocardial infarction (MI). Male Sprague Dawley rats were randomly assigned to either saline or IMD (0.6 µg/kg/h) treatment groups for 4 weeks post-MI. Another group of sham-operated rats served as controls. Cardiac function was assessed by echocardiography, cardiac catheterization and plasma level of B-type natriuretic peptide (BNP). Cardiac sympathetic neural remodeling was assessed by immunohistochemistical study of tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) immunoreactive nerve fibers. The protein expression levels of nerve growth factor (NGF), TH and GAP43 in the ventricular myocardium were studied by western blotting. Ventricular fibrillation threshold (VFT) was determined to evaluate the incidence of ventricular arrhythmia. Oxidative stress was assessed by detecting the activity of superoxide dismutase and the level of malondialdehyde. Compared with rats administrated with saline, IMD significantly improved cardiac function, decreased the plasma BNP level, attenuated sympathetic neural remodeling, increased VFT and suppressed oxidative stress. In conclusion, these results indicated that IMD prevents ventricle remodeling and improves the performance of a failing heart. In addition, IMD attenuated sympathetic neural remodeling and reduced the incidence of ventricular arrhythmia, which may contribute to its anti-oxidative property. These results implicate IMD as a potential therapeutic agent for the treatment of HF. PMID:28627670

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.

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.

Cardiac microvascular rarefaction in hyperthyroidism-induced left ventricle dysfunction.

PubMed

Freitas, Felipe; Estato, Vanessa; Carvalho, Vinícius Frias; Torres, Rafael Carvalho; Lessa, Marcos Adriano; Tibiriçá, Eduardo

2013-10-01

The pathophysiology underlying hyperthyroidism-induced left ventricle (LV) dysfunction and hypertrophy directly involves the heart and indirectly involves the neuroendocrine systems. The effects of hyperthyroidism on the microcirculation are still controversial in experimental models. We investigated the effects of hyperthyroidism on the cardiac function and microcirculation of an experimental rat model. Male Wistar rats (170-250 g) were divided into two groups: the euthyroid group (n = 10), which was treated with 0.9% saline solution, and the hyperthyroid group (n = 10), which was treated with l-thyroxine (600 μg/kg/day, i.p.) during 14 days. An echocardiographic study was performed to evaluate the alterations in cardiac function, structure and geometry. The structural capillary density and the expression of angiotensin II AT1 receptor in the LV were analyzed using histochemistry and immunohistochemistry, respectively. Hyperthyroidism was found to induce profound cardiovascular alterations, such as systolic hypertension, tachycardia, LV dysfunction, cardiac hypertrophy, and myocardial fibrosis. This study demonstrates the existence of structural capillary rarefaction and the down-regulation of the cardiac angiotensin II AT1 receptor in the myocardium of hyperthyroid rats in comparison with euthyroid rats. Microvascular rarefaction may be involved in the pathophysiology of hyperthyroidism-induced cardiovascular alterations. © 2013 John Wiley & Sons Ltd.

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

Postnatal Cardiac Gene Editing Using CRISPR/Cas9 With AAV9-Mediated Delivery of Short Guide RNAs Results in Mosaic Gene Disruption.

PubMed

Johansen, Anne Katrine; Molenaar, Bas; Versteeg, Danielle; Leitoguinho, Ana Rita; Demkes, Charlotte; Spanjaard, Bastiaan; de Ruiter, Hesther; Akbari Moqadam, Farhad; Kooijman, Lieneke; Zentilin, Lorena; Giacca, Mauro; van Rooij, Eva

2017-10-27

CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9)-based DNA editing has rapidly evolved as an attractive tool to modify the genome. Although CRISPR/Cas9 has been extensively used to manipulate the germline in zygotes, its application in postnatal gene editing remains incompletely characterized. To evaluate the feasibility of CRISPR/Cas9-based cardiac genome editing in vivo in postnatal mice. We generated cardiomyocyte-specific Cas9 mice and demonstrated that Cas9 expression does not affect cardiac function or gene expression. As a proof-of-concept, we delivered short guide RNAs targeting 3 genes critical for cardiac physiology, Myh6 , Sav1 , and Tbx20 , using a cardiotropic adeno-associated viral vector 9. Despite a similar degree of DNA disruption and subsequent mRNA downregulation, only disruption of Myh6 was sufficient to induce a cardiac phenotype, irrespective of short guide RNA exposure or the level of Cas9 expression. DNA sequencing analysis revealed target-dependent mutations that were highly reproducible across mice resulting in differential rates of in- and out-of-frame mutations. Finally, we applied a dual short guide RNA approach to effectively delete an important coding region of Sav1 , which increased the editing efficiency. Our results indicate that the effect of postnatal CRISPR/Cas9-based cardiac gene editing using adeno-associated virus serotype 9 to deliver a single short guide RNA is target dependent. We demonstrate a mosaic pattern of gene disruption, which hinders the application of the technology to study gene function. Further studies are required to expand the versatility of CRISPR/Cas9 as a robust tool to study novel cardiac gene functions in vivo. © 2017 American Heart Association, Inc.

Clinical Aspects of Type-1 Long-QT Syndrome by Location, Coding Type, and Biophysical Function of Mutations Involving the KCNQ1 Gene

PubMed Central

Moss, Arthur J.; Shimizu, Wataru; Wilde, Arthur A.M.; Towbin, Jeffrey A.; Zareba, Wojciech; Robinson, Jennifer L.; Qi, Ming; Vincent, G. Michael; Ackerman, Michael J.; Kaufman, Elizabeth S.; Hofman, Nynke; Seth, Rahul; Kamakura, Shiro; Miyamoto, Yoshihiro; Goldenberg, Ilan; Andrews, Mark L.; McNitt, Scott

2012-01-01

Background Type-1 long-QT syndrome (LQTS) is caused by loss-of-function mutations in the KCNQ1-encoded IKs cardiac potassium channel. We evaluated the effect of location, coding type, and biophysical function of KCNQ1 mutations on the clinical phenotype of this disorder. Methods and Results We investigated the clinical course in 600 patients with 77 different KCNQ1 mutations in 101 proband-identified families derived from the US portion of the International LQTS Registry (n=425), the Netherlands’ LQTS Registry (n=93), and the Japanese LQTS Registry (n=82). The Cox proportional hazards survivorship model was used to evaluate the independent contribution of clinical and genetic factors to the first occurrence of time-dependent cardiac events from birth through age 40 years. The clinical characteristics, distribution of mutations, and overall outcome event rates were similar in patients enrolled from the 3 geographic regions. Biophysical function of the mutations was categorized according to dominant-negative (>50%) or haploinsufficiency (≤50%) reduction in cardiac repolarizing IKs potassium channel current. Patients with transmembrane versus C-terminus mutations (hazard ratio, 2.06; P<0.001) and those with mutations having dominant-negative versus haploinsufficiency ion channel effects (hazard ratio, 2.26; P<0.001) were at increased risk for cardiac events, and these genetic risks were independent of traditional clinical risk factors. Conclusions This genotype–phenotype study indicates that in type-1 LQTS, mutations located in the transmembrane portion of the ion channel protein and the degree of ion channel dysfunction caused by the mutations are important independent risk factors influencing the clinical course of this disorder. PMID:17470695

Protective effects of Jiashen Prescription () on myocardial infarction in rats.

PubMed

Zhu, Ming-Jun; Wang, You-Ping; Xie, Shi-Yang; Liu, Wei-Hong; Li, Bin; Wang, Yong-Xia; Wang, He; Zhang, Bo-Li

2015-06-01

To evaluate the effects of Jiashen Prescription (, JSP) on myocardial infarction (MI) size and cardiac function at the early stage of MI in rats. One hundred male Sprague-Dawley rats were subjected to sham-operation or MI induced by ligating the left anterior descending coronary artery. The rats with MI were treated with vehicle, JSP 3 and 6 g/(kg·d), or losartan 10 mg/(kg·d) for 1 week. Compared with the vehicle-treated MI rats, 6 g/(kg·d) JSP reduced MI size 3 days after MI (P<0.05), and attenuated the MI-induced increases in left ventricular end-diastolic and end-systolic dimension and decreases in fractional shortening and ejection fraction 1 week after MI (P<0.05). In addition, 6 g/(kg·d) JSP and losartan were equally effective in reducing MI size and enhancing cardiac functional recovery. JSP reduces MI size and improves cardiac function after MI, suggesting that JSP has potential as a therapy for MI.

Evaluation of training nurses to perform semi-automated three-dimensional left ventricular ejection fraction using a customised workstation-based training protocol.

PubMed

Guppy-Coles, Kristyan B; Prasad, Sandhir B; Smith, Kym C; Hillier, Samuel; Lo, Ada; Atherton, John J

2015-06-01

We aimed to determine the feasibility of training cardiac nurses to evaluate left ventricular function utilising a semi-automated, workstation-based protocol on three dimensional echocardiography images. Assessment of left ventricular function by nurses is an attractive concept. Recent developments in three dimensional echocardiography coupled with border detection assistance have reduced inter- and intra-observer variability and analysis time. This could allow abbreviated training of nurses to assess cardiac function. A comparative, diagnostic accuracy study evaluating left ventricular ejection fraction assessment utilising a semi-automated, workstation-based protocol performed by echocardiography-naïve nurses on previously acquired three dimensional echocardiography images. Nine cardiac nurses underwent two brief lectures about cardiac anatomy, physiology and three dimensional left ventricular ejection fraction assessment, before a hands-on demonstration in 20 cases. We then selected 50 cases from our three dimensional echocardiography library based on optimal image quality with a broad range of left ventricular ejection fractions, which was quantified by two experienced sonographers and the average used as the comparator for the nurses. Nurses independently measured three dimensional left ventricular ejection fraction using the Auto lvq package with semi-automated border detection. The left ventricular ejection fraction range was 25-72% (70% with a left ventricular ejection fraction <55%). All nurses showed excellent agreement with the sonographers. Minimal intra-observer variability was noted on both short-term (same day) and long-term (>2 weeks later) retest. It is feasible to train nurses to measure left ventricular ejection fraction utilising a semi-automated, workstation-based protocol on previously acquired three dimensional echocardiography images. Further study is needed to determine the feasibility of training nurses to acquire three dimensional echocardiography images on real-world patients to measure left ventricular ejection fraction. Nurse-performed evaluation of left ventricular function could facilitate the broader application of echocardiography to allow cost-effective screening and monitoring for left ventricular dysfunction in high-risk populations. © 2014 John Wiley & Sons Ltd.

Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

NASA Astrophysics Data System (ADS)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

Evaluation ofserum free carnitine/acylcarnitine levels and left ventricular systolic functions in children with idiopathic epilepsy receiving valproic acid.

PubMed

Kulhas Celik, Ilknur; Tasdemir, Haydar Ali; Ince, Hülya; Celik, Halil; Sungur, Metin

2018-07-01

In the study, the effect of valproic acid on serum free/acylcarnitine levels and left ventricular systolic function in pediatric patients with idiopathic epilepsy receiving valproic acid was investigated. Patients receiving valproic acid treatment for six months between January 2012 and December 2012 were evaluated. Blood samples were obtained from the participants twice (pretreatment and the sixth month of treatment) and serum-free and acylcarnitine levels (from C2 to C18:1-OH) were measured using tandem mass spectrometry. Cardiac functions (ejection fraction, shortening fraction, cardiac output, left ventricular systolic and diastolic diameters, left atrial diameter, aortic diameter, cardiac output, and myocardial performance index) were evaluated by echocardiography simultaneously. A total of fourty patients, 23 female (57.5%) and 17 male (42.5%), with the diagnosis of idiopathic epilepsy and receiving valproic acid monotherapy were studied. Comparison of serum-free and acylcarnitine levels measured pretreatment and sixth month of treatment revealed a decrease in average C0 and C5:1 (respectively p < 0.001, p = 0.013) and an increase in C2, C3, C5-OH, C8:1 and C4-DC levels (respectively p < 0.001, p < 0.001, p = 0.019, p = 0.013, p < 0.001). Other serum acylcarnitine levels did not change significantly (p > 0.05). No difference was observed in concurrent echocardiographic measurements of left ventricular systolic function (p > 0.05). The study demonstrated that valproic acid treatment results in low levels of free carnitine and changes in some acylcarnitine subgroups but has no influence on left ventricular systolic function. Copyright © 2018 Elsevier B.V. All rights reserved.

Automated Identification of the Heart Wall Throughout the Entire Cardiac Cycle Using Optimal Cardiac Phase for Extracted Features

NASA Astrophysics Data System (ADS)

Takahashi, Hiroki; Hasegawa, Hideyuki; Kanai, Hiroshi

2011-07-01

In most methods for evaluation of cardiac function based on echocardiography, the heart wall is currently identified manually by an operator. However, this task is very time-consuming and suffers from inter- and intraobserver variability. The present paper proposes a method that uses multiple features of ultrasonic echo signals for automated identification of the heart wall region throughout an entire cardiac cycle. In addition, the optimal cardiac phase to select a frame of interest, i.e., the frame for the initiation of tracking, was determined. The heart wall region at the frame of interest in this cardiac phase was identified by the expectation-maximization (EM) algorithm, and heart wall regions in the following frames were identified by tracking each point classified in the initial frame as the heart wall region using the phased tracking method. The results for two subjects indicate the feasibility of the proposed method in the longitudinal axis view of the heart.

Joint multi-object registration and segmentation of left and right cardiac ventricles in 4D cine MRI

NASA Astrophysics Data System (ADS)

Ehrhardt, Jan; Kepp, Timo; Schmidt-Richberg, Alexander; Handels, Heinz

2014-03-01

The diagnosis of cardiac function based on cine MRI requires the segmentation of cardiac structures in the images, but the problem of automatic cardiac segmentation is still open, due to the imaging characteristics of cardiac MR images and the anatomical variability of the heart. In this paper, we present a variational framework for joint segmentation and registration of multiple structures of the heart. To enable the simultaneous segmentation and registration of multiple objects, a shape prior term is introduced into a region competition approach for multi-object level set segmentation. The proposed algorithm is applied for simultaneous segmentation of the myocardium as well as the left and right ventricular blood pool in short axis cine MRI images. Two experiments are performed: first, intra-patient 4D segmentation with a given initial segmentation for one time-point in a 4D sequence, and second, a multi-atlas segmentation strategy is applied to unseen patient data. Evaluation of segmentation accuracy is done by overlap coefficients and surface distances. An evaluation based on clinical 4D cine MRI images of 25 patients shows the benefit of the combined approach compared to sole registration and sole segmentation.

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.

Arrhythmogenic Right Ventricular Cardiomyopathy in an Endurance Athlete Presenting with Ventricular Tachycardia and Normal Right Ventricular Function.

PubMed

Hedley, Jeffrey S; Al Mheid, Ibhar; Alikhani, Zoubin; Pernetz, Maria A; Kim, Jonathan H

2017-08-01

Arrhythmogenic right ventricular cardiomyopathy, a genetically inherited disease that results in fibrofatty replacement of normal cardiac myocytes, has been associated with sudden cardiac death in athletes. Long-term participation in endurance exercise hastens the development of both the arrhythmic and structural arrhythmogenic right ventricular cardiomyopathy phenotypes. We describe the unusual case of a 34-year-old, symptomatic, female endurance athlete who had arrhythmogenic right ventricular cardiomyopathy in the presence of a structurally normal right ventricle. Clinicians should be aware of this infrequent presentation when evaluating athletic patients who have ventricular arrhythmias and normal findings on cardiac imaging studies.

Gender-related differences in β-adrenergic receptor-mediated cardiac remodeling.

PubMed

Zhu, Baoling; Liu, Kai; Yang, Chengzhi; Qiao, Yuhui; Li, Zijian

2016-12-01

Cardiac remodeling is the pathological basis of various cardiovascular diseases. In this study, we found gender-related differences in β-adrenergic receptor (AR)-mediated pathological cardiac remodeling. Cardiac remodeling model was established by subcutaneous injection of isoprenaline (ISO) for 14 days. Heart rate (HR), mean arterial pressure (MAP), and echocardiography were obtained on 7th and 14th days during ISO administration. Myocardial cross-sectional area and the ratio of heart mass to tibia length (HM/TL) were detected to assess cardiac hypertrophy. Picro-Sirius red staining (picric acid + Sirius red F3B) was used to evaluate cardiac fibrosis. Myocardial capillary density was assessed by immunohistochemistry for von Willebrand factor. Further, real-time PCR was used to measure the expression of β1-AR and β2-AR. Results showed that ISO induced cardiac remodeling, the extent of which was different between female and male mice. The extent of increase in cardiac wall thickness, myocardial cross-sectional area, and collagen deposition in females was less than that in males. However, no gender-related difference was observed in HR, MAP, cardiac function, and myocardial capillary density. The distinctive decrease of β2-AR expression, rather than a decrease of β1-AR expression, seemed to result in gender-related differences in cardiac remodeling.

Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: role of autophagy.

PubMed

Guo, Rui; Zhang, Yingmei; Turdi, Subat; Ren, Jun

2013-08-01

Adiponectin (APN), an adipose-derived adipokine, offers cardioprotective effects although the precise mechanism of action remains unclear. This study was designed to examine the role of APN in high fat diet-induced obesity and cardiac pathology. Adult C57BL/6 wild-type and APN knockout mice were fed a low or high fat diet for 22weeks. After 40day feeding, mice were treated with 2mg/kg rapamycin or vehicle every other day for 42days on respective fat diet. Cardiomyocyte contractile and Ca(2+) transient properties were evaluated. Myocardial function was evaluated using echocardiography. Dual energy X-ray absorptiometry was used to evaluate adiposity. Energy expenditure, metabolic rate and physical activity were monitored using a metabolic cage. Lipid deposition, serum triglyceride, glucose tolerance, markers of autophagy and fatty acid metabolism including LC3, p62, Beclin-1, AMPK, mTOR, fatty acid synthase (FAS) were evaluated. High fat diet intake induced obesity, systemic glucose intolerance, cardiac hypertrophy, dampened metabolic ability, cardiac and intracellular Ca(2+) derangements, the effects of which were accentuated by APN knockout. Furthermore, APN deficiency augmented high fat diet-induced upregulation in the autophagy adaptor p62 and the decline in AMPK without affecting high fat diet-induced decrease in LC3II and LC3II-to-LC3I ratio. Neither high fat diet nor APN deficiency altered Beclin-1. Interestingly, rapamycin negated high fat diet-induced/APN-deficiency-accentuated obesity, cardiac hypertrophy and contractile dysfunction as well as AMPK dephosphorylation, mTOR phosphorylation and p62 buildup. Our results collectively revealed that APN deficiency may aggravate high fat diet-induced obesity, metabolic derangement, cardiac hypertrophy and contractile dysfunction possibly through decreased myocardial autophagy. Copyright © 2013 Elsevier B.V. All rights reserved.

Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: Role of autophagy

PubMed Central

Guo, Rui; Zhang, Yingmei; Turdi, Subat; Ren, Jun

2013-01-01

Adiponectin (APN), an adipose-derived adipokine, offers cardioprotective effects although the precise mechanism of action remains unclear. This study was designed to examine the role of APN in high fat diet-induced obesity and cardiac pathology. Adult C57BL/6 wild-type and APN knockout mice were fed a low or high fat diet for 22 weeks. After 40 day feeding, mice were treated with 2 mg/kg rapamycin or vehicle every other day for 42 days on respective fat diet. Cardiomyocyte contractile and Ca2+ transient properties were evaluated. Myocardial function was evaluated using echocardiography. Dual energy X-ray absorptiometry was used to evaluate adiposity. Energy expenditure, metabolic rate and physical activity were monitored using a metabolic cage. Lipid deposition, serum triglyceride, glucose tolerance, markers of autophagy and fatty acid metabolism including LC3, p62, Beclin-1, AMPK, mTOR, fatty acid synthase (FAS) were evaluated. High fat diet intake induced obesity, systemic glucose intolerance, cardiac hypertrophy, dampened metabolic ability, cardiac and intracellular Ca2+ derangements, the effects of which were accentuated by APN knockout. Furthermore, APN deficiency augmented high fat diet-induced upregulation in the autophagy adaptor p62 and the decline in AMPK without affecting high fat diet-induced decrease in LC3II and LC3II-to-LC3I ratio. Neither high fat diet nor APN deficiency altered Beclin-1. Interestingly, rapamycin negated high fat diet-induced/APN-deficiency-accentuated obesity, cardiac hypertrophy and contractile dysfunction as well as AMPK dephosphorylation, mTOR phosphorylation and p62 buildup. Our results collectively revealed that APN deficiency may aggravate high fat diet-induced obesity, metabolic derangement, cardiac hypertrophy and contractile dysfunction possibly through decreased myocardial autophagy. PMID:23524376

Improved Accuracy of Automated Estimation of Cardiac Output Using Circulation Time in Patients with Heart Failure.

PubMed

Dajani, Hilmi R; Hosokawa, Kazuya; Ando, Shin-Ichi

2016-11-01

Lung-to-finger circulation time of oxygenated blood during nocturnal periodic breathing in heart failure patients measured using polysomnography correlates negatively with cardiac function but possesses limited accuracy for cardiac output (CO) estimation. CO was recalculated from lung-to-finger circulation time using a multivariable linear model with information on age and average overnight heart rate in 25 patients who underwent evaluation of heart failure. The multivariable model decreased the percentage error to 22.3% relative to invasive CO measured during cardiac catheterization. This improved automated noninvasive CO estimation using multiple variables meets a recently proposed performance criterion for clinical acceptability of noninvasive CO estimation, and compares very favorably with other available methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Preoperative biomedical risk and depressive symptoms are differently associated with reduced health-related quality of life in patients 1year after cardiac surgery.

PubMed

Patron, Elisabetta; Messerotti Benvenuti, Simone; Palomba, Daniela

2016-01-01

To examine whether preoperative biomedical risk and depressive symptoms were associated with physical and mental components of health-related quality of life (HRQoL) in patients 1year after cardiac surgery. Seventy-five patients completed a psychological evaluation, including the Center for Epidemiological Study of Depression scale, the 12-item Short-Form Physical Component Scale (SF-12-PCS) and Mental Component Scale (SF-12-MCS), the Instrumental Activities of Daily Living questionnaire for depressive symptoms and HRQoL, respectively, before surgery and at 1-year follow-up. Preoperative depressive symptoms predicted the SF-12-PCS (beta=-.22, P<.05) and SF-12-MCS (beta=-.30, P<.04) scores in patients 1year after cardiac surgery, whereas the European System for Cardiac Operative Risk Evaluation was associated with SF-12-PCS (beta=-.28, P<.02), but not SF-12-MCS (beta=.01, P=.97) scores postoperatively. The current findings showed that preoperative depressive symptoms are associated with poor physical and mental components of HRQoL, whereas high biomedical risk predicts reduced physical, but not mental, functioning in patients postoperatively. This study suggests that a preoperative assessment of depressive symptoms in addition to the evaluation of common biomedical risk factors is essential to anticipate which patients are likely to show poor HRQoL after cardiac surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Fusion of 4D echocardiography and cine cardiac magnetic resonance volumes using a salient spatio-temporal analysis

NASA Astrophysics Data System (ADS)

Atehortúa, Angélica; Garreau, Mireille; Romero, Eduardo

2017-11-01

An accurate left (LV) and right ventricular (RV) function quantification is important to support evaluation, diagnosis and prognosis of cardiac pathologies such as the cardiomyopathies. Currently, diagnosis by ultrasound is the most cost-effective examination. However, this modality is highly noisy and operator dependent, hence prone to errors. Therefore, fusion with other cardiac modalities may provide complementary information and improve the analysis of the specific pathologies like cardiomyopathies. This paper proposes an automatic registration between two complementary modalities, 4D echocardiography and Magnetic resonance images, by mapping both modalities to a common space of salience where an optimal registration between them is estimated. The obtained matrix transformation is then applied to the MRI volume which is superimposed to the 4D echocardiography. Manually selected marks in both modalities are used to evaluate the precision of the superimposition. Preliminary results, in three evaluation cases, show the distance between these marked points and the estimated with the transformation is about 2 mm.

Optimized Heart Sampling and Systematic Evaluation of Cardiac Therapies in Mouse Models of Ischemic Injury: Assessment of Cardiac Remodeling and Semi-Automated Quantification of Myocardial Infarct Size.

PubMed

Valente, Mariana; Araújo, Ana; Esteves, Tiago; Laundos, Tiago L; Freire, Ana G; Quelhas, Pedro; Pinto-do-Ó, Perpétua; Nascimento, Diana S

2015-12-02

Cardiac therapies are commonly tested preclinically in small-animal models of myocardial infarction. Following functional evaluation, post-mortem histological analysis is essential to assess morphological and molecular alterations underlying the effectiveness of treatment. However, non-methodical and inadequate sampling of the left ventricle often leads to misinterpretations and variability, making direct study comparisons unreliable. Protocols are provided for representative sampling of the ischemic mouse heart followed by morphometric analysis of the left ventricle. Extending the use of this sampling to other types of in situ analysis is also illustrated through the assessment of neovascularization and cellular engraftment in a cell-based therapy setting. This is of interest to the general cardiovascular research community as it details methods for standardization and simplification of histo-morphometric evaluation of emergent heart therapies. © 2015 by John Wiley & Sons, Inc. Copyright © 2015 John Wiley & Sons, Inc.

Cardiac gene transfer of short hairpin RNA directed against phospholamban effectively knocks down gene expression but causes cellular toxicity in canines.

PubMed

Bish, Lawrence T; Sleeper, Meg M; Reynolds, Caryn; Gazzara, Jeffrey; Withnall, Elanor; Singletary, Gretchen E; Buchlis, George; Hui, Daniel; High, Katherine A; Gao, Guangping; Wilson, James M; Sweeney, H Lee

2011-08-01

Derangements in calcium cycling have been described in failing hearts, and preclinical studies have suggested that therapies aimed at correcting this defect can lead to improvements in cardiac function and survival. One strategy to improve calcium cycling would be to inhibit phospholamban (PLB), the negative regulator of SERCA2a that is upregulated in failing hearts. The goal of this study was to evaluate the safety and efficacy of using adeno-associated virus (AAV)-mediated cardiac gene transfer of short hairpin RNA (shRNA) to knock down expression of PLB. Six dogs were treated with self-complementary AAV serotype 6 (scAAV6) expressing shRNA against PLB. Three control dogs were treated with empty AAV6 capsid, and two control dogs were treated with scAAV6 expressing dominant negative PLB. Vector was delivered via a percutaneously inserted cardiac injection catheter. PLB mRNA and protein expression were analyzed in three of six shRNA dogs between days 16 and 26. The other three shRNA dogs and five control dogs were monitored long-term to assess cardiac safety. PLB mRNA was reduced 16-fold, and PLB protein was reduced 5-fold, with treatment. Serum troponin elevation and depressed cardiac function were observed in the shRNA group only at 4 weeks. An enzyme-linked immunospot assay failed to detect any T cells reactive to AAV6 capsid in peripheral blood mononuclear cells, heart, or spleen. Microarray analysis revealed alterations in cardiac expression of several microRNAs with shRNA treatment. AAV6-mediated cardiac gene transfer of shRNA effectively knocks down PLB expression but is associated with severe cardiac toxicity. Toxicity may result from dysregulation of endogenous microRNA pathways.

Atorvastatin prevents advanced glycation end products (AGEs)-induced cardiac fibrosis via activating peroxisome proliferator-activated receptor gamma (PPAR-γ).

PubMed

Chen, Miao; Li, Hongwei; Wang, Guoxing; Shen, Xuhua; Zhao, Shumei; Su, Wen

2016-04-01

Previous studies have shown that the activation of advanced glycation end products (AGEs) contributed to the cardiac fibrosis in diabetic patients. Although it had been reported that statins have beneficial effects on cardiac fibrosis in hypertension and myocardial ischemia models, their effects on AGEs models have not been studied. We aimed to investigate the effects of atorvastatin (Ator) on the AGEs-induced cardiac fibrosis both in vitro and vivo. Male Sprague-Dawley rats were randomly divided into four groups: Control, AGEs, Ator or AGEs+Ator. The cardiac function was evaluated with the echocardiography at the second and the third month. Fibrosis area, α-SMA and RAGE expression in cardiac tissue were measured. For in vitro study, rat cardiac fibroblasts were treated with PD98059 (ERK inhibitor), Ator or Ator+GW9662 (PPAR-γ antagonist), and then were stimulated with AGEs. Fibroblasts proliferation, ERK1/2, phosphorylated ERK1/2, α-SMA, and RAGE expression were studied. Compared with the control group, in vivo treatment with Ator significantly retarded the AGEs-induced diastolic function and attenuated cardiac fibrosis, α-SMA, and RAGE over expression induced by AGEs. Consistently, Ator prominently downregulated RAGE and α-SMA, while inhibited phosphorylation of ERK1/2 and fibroblast proliferation induced by AGEs in vitro. The GW9662 neutralized these effects of Ator on cardiac fibroblasts stimulated by AGEs. In this study, we demonstrated that AGEs-induced fibroblast proliferation and differentiation were dependent on AGEs-RAGE-ERK1/2 pathway and that atorvastatin could block this pathway via activating PPAR-γ. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiac Gene Transfer of Short Hairpin RNA Directed Against Phospholamban Effectively Knocks Down Gene Expression but Causes Cellular Toxicity in Canines

PubMed Central

Sleeper, Meg M.; Reynolds, Caryn; Gazzara, Jeffrey; Withnall, Elanor; Singletary, Gretchen E.; Buchlis, George; Hui, Daniel; High, Katherine A.; Gao, Guangping; Wilson, James M.; Sweeney, H. Lee

2011-01-01

Abstract Derangements in calcium cycling have been described in failing hearts, and preclinical studies have suggested that therapies aimed at correcting this defect can lead to improvements in cardiac function and survival. One strategy to improve calcium cycling would be to inhibit phospholamban (PLB), the negative regulator of SERCA2a that is upregulated in failing hearts. The goal of this study was to evaluate the safety and efficacy of using adeno-associated virus (AAV)-mediated cardiac gene transfer of short hairpin RNA (shRNA) to knock down expression of PLB. Six dogs were treated with self-complementary AAV serotype 6 (scAAV6) expressing shRNA against PLB. Three control dogs were treated with empty AAV6 capsid, and two control dogs were treated with scAAV6 expressing dominant negative PLB. Vector was delivered via a percutaneously inserted cardiac injection catheter. PLB mRNA and protein expression were analyzed in three of six shRNA dogs between days 16 and 26. The other three shRNA dogs and five control dogs were monitored long-term to assess cardiac safety. PLB mRNA was reduced 16-fold, and PLB protein was reduced 5-fold, with treatment. Serum troponin elevation and depressed cardiac function were observed in the shRNA group only at 4 weeks. An enzyme-linked immunospot assay failed to detect any T cells reactive to AAV6 capsid in peripheral blood mononuclear cells, heart, or spleen. Microarray analysis revealed alterations in cardiac expression of several microRNAs with shRNA treatment. AAV6-mediated cardiac gene transfer of shRNA effectively knocks down PLB expression but is associated with severe cardiac toxicity. Toxicity may result from dysregulation of endogenous microRNA pathways. PMID:21542669

Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials.

PubMed

Holubkov, Richard; Clark, Amy E; Moler, Frank W; Slomine, Beth S; Christensen, James R; Silverstein, Faye S; Meert, Kathleen L; Pollack, Murray M; Dean, J Michael

2015-01-01

The Therapeutic Hypothermia After Pediatric Cardiac Arrest trials will determine whether therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition, in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during Therapeutic Hypothermia After Pediatric Cardiac Arrest protocol development. Consensus assessment of potential outcomes and evaluation timepoints. None. We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. Twelve months after arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in Vineland Adaptive Behavior Scales Second Edition from prearrest level, measured as quasicontinuous with death and vegetative status being worst-possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes because of easier interpretability and favored outcomes based solely on postarrest status because of concerns about accurate parental assessment of prearrest status and differing clinical impact of a given Vineland Adaptive Behavior Scales Second Edition change depending on prearrest status. Simulations found only modest power loss from categorizing or dichotomizing quasicontinuous outcomes because of high expected mortality. The primary outcome selected was survival with 12-month Vineland Adaptive Behavior Scales Second Edition no less than two SD below a reference population mean (70 points), necessarily evaluated only among children with prearrest Vineland Adaptive Behavior Scales Second Edition greater than or equal to 70. Two secondary efficacy outcomes, 12-month survival and quasicontinuous Vineland Adaptive Behavior Scales Second Edition change from prearrest level, will be evaluated among all randomized children, including those with compromised function prearrest. Extensive discussion of optimal efficacy assessment timing, and of the advantages versus drawbacks of incorporating prearrest status and using quasicontinuous versus simpler outcomes, was highly beneficial to the final Therapeutic Hypothermia After Pediatric Cardiac Arrest design. A relatively simple, binary primary outcome evaluated at 12 months was selected, with two secondary outcomes that address the potential disadvantages of primary outcome.

Cardiac iron load and function in transfused patients treated with deferasirox (the MILE study).

PubMed

Ho, P Joy; Tay, Lay; Teo, Juliana; Marlton, Paula; Grigg, Andrew; St Pierre, Tim; Brown, Greg; Badcock, Caro-Anne; Traficante, Robert; Gervasio, Othon L; Bowden, Donald K

2017-02-01

To assess the effect of iron chelation therapy with deferasirox on cardiac iron and function in patients with transfusion-dependent thalassemia major, sickle cell disease (SCD), and myelodysplastic syndromes (MDS). This phase IV, single-arm, open-label study over 53 wk evaluated the change in cardiac and liver iron load with deferasirox (up to 40 mg/kg/d), measured by magnetic resonance imaging (MRI). Cardiac iron load (myocardial T2*) significantly improved (P = 0.002) overall (n = 46; n = 36 thalassemia major, n = 4 SCD, n = 6 MDS). Results were significant for patients with normal and moderate baseline cardiac iron (P = 0.017 and P = 0.015, respectively), but not in the five patients with severe cardiac iron load. Liver iron concentration (LIC) significantly decreased overall [mean LIC 10.4 to 8.2 mg Fe/g dry tissue (dw); P = 0.024], particularly in those with baseline LIC >7 mg Fe/g dw (19.9 to 15.6 mg Fe/g dw; P = 0.002). Furthermore, myocardial T2* significantly increased in patients with LIC <7 mg Fe/g dw, but not in those with a higher LIC. Safety was consistent with previous reports. Once-daily deferasirox over 1 yr significantly increased myocardial T2* and reduced LIC. This confirms that single-agent deferasirox is effective in the management of cardiac iron, especially for patients with myocardial T2* >10 ms (Clinicaltrials.gov identifier: NCT00673608). © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Blanck, Oliver, E-mail: oliver.blanck@uksh.de; CyberKnife Center Northern Germany, Guestrow; Bode, Frank

Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarringmore » of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.« less

Multi-Physics MRI-Based Two-Layer Fluid-Structure Interaction Anisotropic Models of Human Right and Left Ventricles with Different Patch Materials: Cardiac Function Assessment and Mechanical Stress Analysis

PubMed Central

Tang, Dalin; Yang, Chun; Geva, Tal; Gaudette, Glenn; del Nido, Pedro J.

2011-01-01

Multi-physics right and left ventricle (RV/LV) fluid-structure interaction (FSI) models were introduced to perform mechanical stress analysis and evaluate the effect of patch materials on RV function. The FSI models included three different patch materials (Dacron scaffold, treated pericardium, and contracting myocardium), two-layer construction, fiber orientation, and active anisotropic material properties. The models were constructed based on cardiac magnetic resonance (CMR) images acquired from a patient with severe RV dilatation and solved by ADINA. Our results indicate that the patch model with contracting myocardium leads to decreased stress level in the patch area, improved RV function and patch area contractility. PMID:21765559

Sinomenine prevents the development of cardiomyopathy in diabetic rats by inhibiting inflammatory responses and blocking activation of NF-κB.

PubMed

Jiang, Cheng; Tong, Yun-Long; Zhang, Dan; Liu, Li-Zhi; Wang, Ju-Fei

2017-01-01

Diabetic cardiomyopathy is a severe complication of diabetes mellitus (DM). The goal of current work was to study the effects of sinomenine on streptozotocin-induced cardiomyopathy in rats. DM in rats was induced by intraperitoneal injection of streptozotocin. Cardiac function was evaluated by measuring left ventricle end-diastolic diameter, left ventricle end-systolic diameter and ejection fraction. Cardiac inflammation was evaluated by the degree of infiltration of T lymphocytes and the levels of pro-inflammatory cytokines. Sinomenine attenuated diabetic symptoms without affecting plasma glucose. Cardiac dysfunction in the sinomenine-treated diabetic rats was significantly improved, as reflected by decreased levels of left ventricle end-diastolic diameter, left ventricle end systolic diameter and an increased level of ejection fraction. Sinomenine observably reduced cardiomyocyte hypertrophy in DM rats. Moreover, sinomenine reduced infiltration of CD3+ and CD68+ positive cells and decreased the levels of tumor necrosis factor-α, interlukin-1 and interlukin-6. Finally, sinomenine-treated rats showed a reduced expression of NF-κB and an increased expression of IκB in the myocardium compared with the myocardium of untreated diabetic rats. Our results indicate sinomenine significantly improves cardiac function in diabetic rats, which may be attributed to the deactivation of NF-κB and the blockade of inflammatory cytokine-mediated immune reactions.

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.

Normal and Pathological NCAT Image and PhantomData Based onPhysiologically Realistic Left Ventricle Finite-Element Models

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

Veress, Alexander I.; Segars, W. Paul; Weiss, Jeffrey A.

2006-08-02

The 4D NURBS-based Cardiac-Torso (NCAT) phantom, whichprovides a realistic model of the normal human anatomy and cardiac andrespiratory motions, is used in medical imaging research to evaluate andimprove imaging devices and techniques, especially dynamic cardiacapplications. One limitation of the phantom is that it lacks the abilityto accurately simulate altered functions of the heart that result fromcardiac pathologies such as coronary artery disease (CAD). The goal ofthis work was to enhance the 4D NCAT phantom by incorporating aphysiologically based, finite-element (FE) mechanical model of the leftventricle (LV) to simulate both normal and abnormal cardiac motions. Thegeometry of the FE mechanical modelmore » was based on gated high-resolutionx-ray multi-slice computed tomography (MSCT) data of a healthy malesubject. The myocardial wall was represented as transversely isotropichyperelastic material, with the fiber angle varying from -90 degrees atthe epicardial surface, through 0 degreesat the mid-wall, to 90 degreesat the endocardial surface. A time varying elastance model was used tosimulate fiber contraction, and physiological intraventricular systolicpressure-time curves were applied to simulate the cardiac motion over theentire cardiac cycle. To demonstrate the ability of the FE mechanicalmodel to accurately simulate the normal cardiac motion as well abnormalmotions indicative of CAD, a normal case and two pathologic cases weresimulated and analyzed. In the first pathologic model, a subendocardialanterior ischemic region was defined. A second model was created with atransmural ischemic region defined in the same location. The FE baseddeformations were incorporated into the 4D NCAT cardiac model through thecontrol points that define the cardiac structures in the phantom whichwere set to move according to the predictions of the mechanical model. Asimulation study was performed using the FE-NCAT combination toinvestigate how the differences in contractile function between thesubendocardial and transmural infarcts manifest themselves in myocardialSPECT images. The normal FE model produced strain distributions that wereconsistent with those reported in the literature and a motion consistentwith that defined in the normal 4D NCAT beating heart model based ontagged MRI data. The addition of a subendocardial ischemic region changedthe average transmural circumferential strain from a contractile value of0.19 to a tensile value of 0.03. The addition of a transmural ischemicregion changed average circumferential strain to a value of 0.16, whichis consistent with data reported in the literature. Model resultsdemonstrated differences in contractile function between subendocardialand transmural infarcts and how these differences in function aredocumented in simulated myocardial SPECT images produced using the 4DNCAT phantom. In comparison to the original NCAT beating heart model, theFE mechanical model produced a more accurate simulation for the cardiacmotion abnormalities. Such a model, when incorporated into the 4D NCATphantom, has great potential for use in cardiac imaging research. Withits enhanced physiologically-based cardiac model, the 4D NCAT phantom canbe used to simulate realistic, predictive imaging data of a patientpopulation with varying whole-body anatomy and with varying healthy anddiseased states of the heart that will provide a known truth from whichto evaluate and improve existing and emerging 4D imaging techniques usedin the diagnosis of cardiac disease.« less

Cardiac structure and function in relation to cardiovascular risk factors in Chinese

PubMed Central

2012-01-01

Background Cardiac structure and function are well-studied in Western countries. However, epidemiological data is still scarce in China. Methods Our study was conducted in the framework of cardiovascular health examinations for the current and retired employees of a factory and their family members. According to the American Society of Echocardiography recommendations, we performed echocardiography to evaluate cardiac structure and function, including left atrial volume, left ventricular hypertrophy and diastolic dysfunction. Results The 843 participants (43.0 years) included 288 (34.2%) women, and 191 (22.7%) hypertensive patients, of whom 82 (42.9%) took antihypertensive drugs. The prevalence of left atrial enlargement, left ventricular hypertrophy and concentric remodeling was 2.4%, 5.0% and 12.7%, respectively. The prevalence of mild and moderate-to-severe left ventricular diastolic dysfunction was 14.2% and 3.3%, respectively. The prevalence of these cardiac abnormalities significantly (P ≤ 0.002) increased with age, except for the moderate-to-severe left ventricular diastolic dysfunction. After adjustment for age, gender, body height and body weight, left atrial enlargement was associated with plasma glucose (P = 0.009), and left ventricular hypertrophy and diastolic dysfunction were significantly associated with systolic and diastolic blood pressure (P ≤ 0.03), respectively. Conclusions The prevalence of cardiac structural and functional abnormalities increased with age in this Chinese population. Current drinking and plasma glucose had an impact on left atrial enlargement, whereas systolic and diastolic blood pressures were major correlates for left ventricular hypertrophy and diastolic dysfunction, respectively. PMID:23035836

Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

PubMed

Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

2014-11-01

Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

Obscurin Targets Ankyrin-B and Protein Phosphatase 2A to the Cardiac M-line*

PubMed Central

Cunha, Shane R.; Mohler, Peter J.

2008-01-01

Ankyrin-B targets ion channels and transporters in excitable cells. Dysfunction in ankyrin-B-based pathways results in defects in cardiac physiology. Despite a wealth of knowledge regarding the role of ankyrin-B for cardiac function, little is known regarding the mechanisms underlying ankyrin-B regulation. Moreover, the pathways underlying ankyrin-B targeting in heart are unclear. We report that alternative splicing regulates ankyrin-B localization and function in cardiomyocytes. Specifically, we identify a novel exon (exon 43′) in the ankyrin-B regulatory domain that mediates interaction with the Rho-GEF obscurin. Ankyrin-B transcripts harboring exon 43′ represent the primary cardiac isoform in human and mouse. We demonstrate that ankyrin-B and obscurin are co-localized at the M-line of myocytes and co-immunoprecipitate from heart. We define the structural requirements for ankyrin-B/obscurin interaction to two motifs in the ankyrin-B regulatory domain and demonstrate that both are critical for obscurin/ankyrin-B interaction. In addition, we demonstrate that interaction with obscurin is required for ankyrin-B M-line targeting. Specifically, both obscurin-binding motifs are required for the M-line targeting of a GFP-ankyrin-B regulatory domain. Moreover, this construct acts as a dominant-negative by competing with endogenous ankyrin-B for obscurin-binding at the M-line, thus providing a powerful new tool to evaluate the function of obscurin/ankyrin-B interactions. With this new tool, we demonstrate that the obscurin/ankyrin-B interaction is critical for recruitment of PP2A to the cardiac M-line. Together, these data provide the first evidence for the molecular basis of ankyrin-B and PP2A targeting and function at the cardiac M-line. Finally, we report that ankyrin-B R1788W is localized adjacent to the ankyrin-B obscurin-binding motif and increases binding activity for obscurin. In summary, our new findings demonstrate that ANK2 is subject to alternative splicing that gives rise to unique polypeptides with diverse roles in cardiac function. PMID:18782775

Left ventricular diastolic function in workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement

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

Poręba, Rafał, E-mail: sogood@poczta.onet.pl; Skoczyńska, Anna; Gać, Paweł

2012-09-15

The aim of the study was to evaluate left ventricular diastolic function in workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement. The studies included 115 workers (92 men and 23 women) occupationally exposed to mercury vapour without clinical presentation of cardiac involvement (mean age: 47.83 ± 8.29). Blood samples were taken to determine blood lipid profile, urine was collected to estimate mercury concentration (Hg-U) and echocardiographic examination was performed to evaluate diastolic function of the left ventricle. In the entire group of workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement, Spearman correlationsmore » analysis demonstrated the following significant linear relationships: between body mass index (BMI) and ratio of maximal early diastolic mitral flow velocity/early diastolic mitral annular velocity (E/E') (r = 0.32, p < 0.05), between serum HDL concentration and E/E' (r = − 0.22, p < 0.05), between Hg-U and E/E' (r = 0.35, p < 0.05), between Hg-U and isovolumetric relaxation time (IVRT') (r = 0.41, p < 0.05), between Hg-U and ratio of maximal early diastolic mitral flow velocity/maximal late diastolic mitral flow velocity (E/A) (r = − 0.31, p < 0.05) and between serum HDL concentration and E/A (r = 0.43, p < 0,05). In logistic regression analysis it as shown that independent factors of left ventricular diastolic dysfunction risk in the study group included a higher urine mercury concentration, a higher value of BMI and a lower serum HDL concentration (OR{sub Hg}-{sub U} = 1.071, OR{sub BMI} = 1.200, OR{sub HDL} = 0.896, p < 0.05). Summing up, occupational exposure to mercury vapour may be linked to impaired left ventricular diastolic function in workers without clinical presentation of cardiac involvement. -- Highlights: ► Study aimed at evaluation of LVDD in workers occupationally exposed to Hg. ► There was significant linear relationships between Hg-U and E/E'. ► Independent risk factor of LVDD in study group included higher Hg-U. ► Independent risk factor of LVDD in study group included higher BMI and lower HDL. ► Occupational exposure to Hg may be linked to LVDD.« less

Indonesian herbal medicine prevents hypertension-induced left ventricular hypertrophy by diminishing NADPH oxidase-dependent oxidative stress.

PubMed

Sulistyowati, Erna; Hsu, Jong-Hau; Cheng, Yuan-Bin; Chang, Fang-Rong; Chen, Ying-Fu; Yeh, Jwu-Lai

2017-10-17

Indonesian herbal medicine Centella asiatica , Justicia gendarussa and Imperata cylindrica decoction (CJID) are known to be efficacious for hypertension. Oxidative stress plays an important role in hypertension-induced left ventricular hypertrophy (H-LVH). This study evaluated whether CJID inhibit cardiac remodeling in spontaneously hypertensive rats (SHRs) through mechanism of oxidative stress-related cardiac-NADPH oxidase (NOXs) pathway: NOX1, NOX2 and NOX4. Forty-weeks-old SHRs and normotensive-WKY rats, were both randomly divided into 2 groups: CJID and control. All rats were treated for 5 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured. LV morphology, function and performance were assessed by histological staining and echocardiography. Serum and cardiac superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were assessed. Cardiac superoxide and hydrogen peroxide (H 2 O 2 ) productions, protein expressions of SOD2, SOD3, NOX1, NOX2 and NOX4 were also determined. We found that SBP and HR were significantly decreased in SHRs-treated group. Echocardiography showed that CJID significantly improved LV morphometry and function. CJID decreased MDA level, but increased SOD activity. Cardiac superoxide and H 2 O 2 generation were decreased in SHRs-treated group. CJID caused cardiac SODs expressions to be increased but NOXs expressions to be suppressed. In conclusion, CJID prevents H-LVH by reducing reactive oxygen species production via the NOXs-dependent pathway.

Indonesian herbal medicine prevents hypertension-induced left ventricular hypertrophy by diminishing NADPH oxidase-dependent oxidative stress

PubMed Central

Sulistyowati, Erna; Hsu, Jong-Hau; Cheng, Yuan-Bin; Chang, Fang-Rong; Chen, Ying-Fu; Yeh, Jwu-Lai

2017-01-01

Indonesian herbal medicine Centella asiatica, Justicia gendarussa and Imperata cylindrica decoction (CJID) are known to be efficacious for hypertension. Oxidative stress plays an important role in hypertension-induced left ventricular hypertrophy (H-LVH). This study evaluated whether CJID inhibit cardiac remodeling in spontaneously hypertensive rats (SHRs) through mechanism of oxidative stress-related cardiac-NADPH oxidase (NOXs) pathway: NOX1, NOX2 and NOX4. Forty-weeks-old SHRs and normotensive-WKY rats, were both randomly divided into 2 groups: CJID and control. All rats were treated for 5 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured. LV morphology, function and performance were assessed by histological staining and echocardiography. Serum and cardiac superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were assessed. Cardiac superoxide and hydrogen peroxide (H2O2) productions, protein expressions of SOD2, SOD3, NOX1, NOX2 and NOX4 were also determined. We found that SBP and HR were significantly decreased in SHRs-treated group. Echocardiography showed that CJID significantly improved LV morphometry and function. CJID decreased MDA level, but increased SOD activity. Cardiac superoxide and H2O2 generation were decreased in SHRs-treated group. CJID caused cardiac SODs expressions to be increased but NOXs expressions to be suppressed. In conclusion, CJID prevents H-LVH by reducing reactive oxygen species production via the NOXs-dependent pathway. PMID:29156835

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.

Safety: the heart of the matter.

PubMed

Hayat, Sajad A; Senior, Roxy

2005-08-01

An integral part of evaluation of cardiac disease in modern day medicine is echocardiography. It has made great strides since the initial collaboration of Dr. Helmut Hertz and Dr. Inge Edler. In its modern day form, echocardiography maintains a legacy of a bedside utility while adopting many of the technologic advances ushered in by the digital era. As a result, it boasts a broad and growing spectrum of application including routine use in primary cardiac diagnosis and screening, therapeutic assessment, and guidance of interventional and surgical procedures. With the advent of ultrasound contrast agents it is now arguably the most complete 'one-stop' investigational tool to assess cardiac structure, function and perfusion. However, has it maintained its safety profile? The familiar and oft quoted dictum in medicine of "first do no harm" is of great importance for any diagnostic tool and patient safety should remain a primary consideration for any new investigational technique. In this issue Cosyns' et al. have examined whether some of the theoretical and in vitro experimental concerns surrounding myocardial injury during and following contrast echocardiography result in any detectable change in cardiac function.

Thymosin β4: multiple functions in protection, repair and regeneration of the mammalian heart.

PubMed

Bollini, Sveva; Riley, Paul R; Smart, Nicola

2015-01-01

Despite recent improvements in interventional medicine, cardiovascular disease still represents the major cause of morbidity worldwide, with myocardial infarction being the most common cardiac injury. This has sustained the development of several regenerative strategies based on the use of stem cells and tissue engineering approaches in order to achieve cardiac repair and regeneration by enhancing coronary neovascularization, modulating acute inflammation and supporting myocardial regeneration to provide new functional muscle. The actin monomer binding peptide, Thymosin β4 (Tβ4), has recently been described as a powerful regenerative agent with angiogenic, anti-inflammatory and cardioprotective effects on the heart and which specifically acts on its resident cardiac progenitor cells. In this review we will discuss the state of the art regarding the many roles of Tβ4 in preserving and regenerating the mammalian heart, with specific attention to its ability to activate the quiescent adult epicardium and specific subsets of epicardial progenitor cells for repair. The therapeutic potential of Tβ4 for the treatment of cardiac failure is herein evaluated alongside existing, emerging and prospective novel treatments.

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

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.

Cardiac-specific knockout of ETA receptor mitigates low ambient temperature-induced cardiac hypertrophy and contractile dysfunction

PubMed Central

Zhang, Yingmei; Li, Linlin; Hua, Yinan; Nunn, Jennifer M.; Dong, Feng; Yanagisawa, Masashi; Ren, Jun

2012-01-01

Cold exposure is associated with oxidative stress and cardiac dysfunction. The endothelin (ET) system, which plays a key role in myocardial homeostasis, may participate in cold exposure-induced cardiovascular dysfunction. This study was designed to examine the role of ET-1 in cold stress-induced cardiac geometric and contractile responses. Wild-type (WT) and ETA receptor knockout (ETAKO) mice were assigned to normal or cold exposure (4°C) environment for 2 and 5 weeks prior to evaluation of cardiac geometry, contractile, and intracellular Ca2+ properties. Levels of the temperature sensor transient receptor potential vanilloid (TRPV1), mitochondrial proteins for biogenesis and oxidative phosphorylation, including UCP2, HSP90, and PGC1α were evaluated. Cold stress triggered cardiac hypertrophy, depressed myocardial contractile capacity, including fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, reduced intracellular Ca2+ release, prolonged intracellular Ca2+ decay and relengthening duration, generation of ROS and superoxide, as well as apoptosis, the effects of which were blunted by ETAKO. Western blotting revealed downregulated TRPV1 and PGC1α as well as upregulated UCP2 and activation of GSK3β, GATA4, and CREB in cold-stressed WT mouse hearts, which were obliterated by ETAKO. Levels of HSP90, an essential regulator for thermotolerance, were unchanged. The TRPV1 agonist SA13353 attenuated whereas TRPV1 antagonist capsazepine mimicked cold stress- or ET-1-induced cardiac anomalies. The GSK3β inhibitor SB216763 ablated cold stress-induced cardiac contractile (but not remodeling) changes and ET-1-induced TRPV1 downregulation. These data suggest that ETAKO protects against cold exposure-induced cardiac remodeling and dysfunction mediated through TRPV1 and mitochondrial function. PMID:22442497

Cardiac dysfunction in heart failure: the cardiologist's love affair with time.

PubMed

Brutsaert, Dirk L

2006-01-01

Translating research into clinical practice has been a challenge throughout medical history. From the present review, it should be clear that this is particularly the case for heart failure. As a consequence, public awareness of this disease has been disillusionedly low, despite its prognosis being worse than that of most cancers and many other chronic diseases. We explore how over the past 150 years since Ludwig and Marey concepts about the evaluation of cardiac performance in patients with heart failure have emerged. From this historical-physiologic perspective, we have seen how 3 increasingly reductionist approaches or schools of thought have evolved in parallel, that is, an input-output approach, a hemodynamic pump approach, and a muscular pump approach. Each one of these has provided complementary insights into the pathophysiology of heart failure and has resulted in measurements or derived indices, some of which still being in use in present-day cardiology. From the third, most reductionist muscular pump approach, we have learned that myocardial and ventricular relaxation properties as well as temporal and spatial nonuniformities have been largely overlooked in the 2 other, input-output and hemodynamic pump, approaches. A key message from the present review is that relaxation and nonuniformities can be fully understood only from within the time-space continuum of cardiac pumping. As cyclicity and rhythm are, in some way, the most basic aspects of cardiac function, considerations of time should dominate over any measurement of cardiac performance as a muscular pump. Any measurement that is blind for the arrow of cardiac time should therefore be interpreted with caution. We have seen how the escape from the time domain-as with the calculation of LV ejection fraction-fascinating though as it may be, has undoubtedly served to hinder a rational scientific debate on the recent, so-called systolic-diastolic heart failure controversy. Lacking appreciation of early relaxation abnormalities and inappropriate degrees of nonuniformities has, indeed, led to some unfortunate misunderstandings about the pathophysiologic time progression of heart failure, in particular, heart failure with compensated hemodynamic pump function (ie, with normal or preserved LV ejection fraction). We have seen that with the introduction of newer powerful diagnostic techniques, as, for example, TDI and MRI, to evaluate ventricular "muscular pump" function, this debate can now be held in a more serene physiologic context. These aspects will be elaborated further in subsequent chapter papers of this symposium. With ongoing stem and other cell-based therapies and future reductionistic insights into cardiac cellular performance, we foresee the emergence of a fourth simple-parallel school of thought viewing the heart as a network of communicating different cell types, that is, cardiomyocytes, endothelial cells, fibroblasts, neurons. In this postgenomic age with the introduction of the rapidly evolving discipline of in vivo molecular imaging techniques, we anticipate that novel measurements of cardiac performance in patients with heart failure will soon become available and complement biopsy and other already available cardiac cellular biomarkers (cardiac troponin I; creatine kinase-MB; myoglobin; BNP). Through the use of these novel biomarkers as a fourth diagnostic track in the evaluation of cardiac performance in patients with heart failure, we will soon be able to increasingly understand the behavior of the heart as a complex biologic system-in other words, how these "low-level" biologic functions and signal transduction pathways at a cellular level contribute to the above "high-level" or system-level approach of cardiac performance at the muscular, the hemodynamic, and the input-output pump system levels and, hopefully, how they could contribute to an early diagnosis of chronic heart failure, in patients.

Triiodothyronine Facilitates Weaning From Extracorporeal Membrane Oxygenation by Improved Mitochondrial Substrate Utilization

PubMed Central

Files, Matthew D.; Kajimoto, Masaki; O'Kelly Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Des Rosiers, Christine; Isern, Nancy; Portman, Michael A.

2014-01-01

Background Extracorporeal membrane oxygenation (ECMO) provides a bridge to recovery after myocardial injury in infants and children, yet morbidity and mortality remain high. Weaning from the circuit requires adequate cardiac contractile function, which can be impaired by metabolic disturbances induced either by ischemia‐reperfusion and/or by ECMO. We tested the hypothesis that although ECMO partially ameliorates metabolic abnormalities induced by ischemia‐reperfusion, these abnormalities persist or recur with weaning. We also determined if thyroid hormone supplementation (triiodothyronine) during ECMO improves oxidative metabolism and cardiac function. Methods and Results Neonatal piglets underwent transient coronary ischemia to induce cardiac injury then were separated into 4 groups based on loading status. Piglets without coronary ischemia served as controls. We infused into the left coronary artery [2‐13C]pyruvate and [13C6, 15N]l‐leucine to evaluate oxidative metabolism by gas chromatography‐mass spectroscopy and nuclear magnetic resonance methods. ECMO improved survival, increased oxidative substrate contribution through pyruvate dehydrogenase, reduced succinate and fumarate accumulation, and ameliorated ATP depletion induced by ischemia. The functional and metabolic benefit of ECMO was lost with weaning, yet triiodothyronine supplementation during ECMO restored function, increased relative pyruvate dehydrogenase flux, reduced succinate and fumarate, and preserved ATP stores. Conclusions Although ECMO provides metabolic rest by decreasing energy demand, metabolic impairments persist, and are exacerbated with weaning. Treating ECMO‐induced thyroid depression with triiodothyronine improves substrate flux, myocardial oxidative capacity and cardiac contractile function. This translational model suggests that metabolic targeting can improve weaning. PMID:24650924

Triiodothyronine facilitates weaning from extracorporeal membrane oxygenation by improved mitochondrial substrate utilization.

PubMed

Files, Matthew D; Kajimoto, Masaki; O'Kelly Priddy, Colleen M; Ledee, Dolena R; Xu, Chun; Des Rosiers, Christine; Isern, Nancy; Portman, Michael A

2014-03-20

Extracorporeal membrane oxygenation (ECMO) provides a bridge to recovery after myocardial injury in infants and children, yet morbidity and mortality remain high. Weaning from the circuit requires adequate cardiac contractile function, which can be impaired by metabolic disturbances induced either by ischemia-reperfusion and/or by ECMO. We tested the hypothesis that although ECMO partially ameliorates metabolic abnormalities induced by ischemia-reperfusion, these abnormalities persist or recur with weaning. We also determined if thyroid hormone supplementation (triiodothyronine) during ECMO improves oxidative metabolism and cardiac function. Neonatal piglets underwent transient coronary ischemia to induce cardiac injury then were separated into 4 groups based on loading status. Piglets without coronary ischemia served as controls. We infused into the left coronary artery [2-(13)C]pyruvate and [(13)C6, (15)N]l-leucine to evaluate oxidative metabolism by gas chromatography-mass spectroscopy and nuclear magnetic resonance methods. ECMO improved survival, increased oxidative substrate contribution through pyruvate dehydrogenase, reduced succinate and fumarate accumulation, and ameliorated ATP depletion induced by ischemia. The functional and metabolic benefit of ECMO was lost with weaning, yet triiodothyronine supplementation during ECMO restored function, increased relative pyruvate dehydrogenase flux, reduced succinate and fumarate, and preserved ATP stores. Although ECMO provides metabolic rest by decreasing energy demand, metabolic impairments persist, and are exacerbated with weaning. Treating ECMO-induced thyroid depression with triiodothyronine improves substrate flux, myocardial oxidative capacity and cardiac contractile function. This translational model suggests that metabolic targeting can improve weaning.

The importance of integrated left atrial evaluation: From hypertension to heart failure with preserved ejection fraction.

PubMed

Beltrami, Matteo; Palazzuoli, Alberto; Padeletti, Luigi; Cerbai, Elisabetta; Coiro, Stefano; Emdin, Michele; Marcucci, Rossella; Morrone, Doralisa; Cameli, Matteo; Savino, Ketty; Pedrinelli, Roberto; Ambrosio, Giuseppe

2018-02-01

Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies. © 2017 John Wiley & Sons Ltd.

Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

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

Li, Zhao; Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu

2012-08-31

Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiacmore » TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.« less

Evaluation of athletes with complex congenital heart disease.

PubMed

Bates, Benjamin A; Richards, Camille; Hall, Michael; Kerut, Edmund K; Campbell, William; McMullan, Michael R

2017-06-01

As a result of improvements in congenital heart surgery, there are more adults alive today with congenital heart disease (CHD) than children. Individuals with cardiac birth defects may be able to participate in physical activities but require proper cardiovascular evaluation. The American Heart Association and American College of Cardiology released guidelines in 2015 for athletes with cardiovascular abnormalities. The guidelines express that although restriction from competitive athletics may be indicated for some, the majority of individuals with CHD can and should engage in some form of physical activity. This case study demonstrates the importance of combining all aspects of history, physical examination, ECG, and imaging modalities to evaluate cardiac anatomy and function in young athletes with complex CHD. © 2017, Wiley Periodicals, Inc.

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

Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease.

PubMed

Sano, Toshikazu; Ousaka, Daiki; Goto, Takuya; Ishigami, Shuta; Hirai, Kenta; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2018-03-30

Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved ejection fraction (EF) or reduced EF was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of heart failure with preserved EF and heart failure with reduced EF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4±10.0% versus +1.6±6.4%, P =0.03; stage 3: +7.9±7.5% versus -1.1±5.5%, P <0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (log-rank P =0.225), whereas overall patients treated by CDCs had lower incidences of late failure ( P =0.022), adverse events ( P =0.013), and catheter intervention ( P =0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI, 0.179-0.942; P =0.036). Notably, CDC infusion reduced mortality ( P =0.038) and late complications ( P <0.05) in patients with heart failure with reduced EF but not with heart failure with preserved EF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes. CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with heart failure with reduced EF but not heart failure with preserved EF treated by CDCs resulted in significant improvement in clinical outcome. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750. © 2018 American Heart Association, Inc.

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

State of the art in forensic investigation of sudden cardiac death.

PubMed

Oliva, Antonio; Brugada, Ramon; D'Aloja, Ernesto; Boschi, Ilaria; Partemi, Sara; Brugada, Josep; Pascali, Vincenzo L

2011-03-01

The sudden death of a young person is a devastating event for both the family and community. Over the last decade, significant advances have been made in understanding both the clinical and genetic basis of sudden cardiac death. Many of the causes of sudden death are due to genetic heart disorders, which can lead to both structural (eg, hypertrophic cardiomyopathy) and arrhythmogenic abnormalities (eg, familial long QT syndrome, Brugada syndrome). Most commonly, sudden cardiac death can be the first presentation of an underlying heart problem, leaving the family at a loss as to why an otherwise healthy young person has died. Not only is this a tragic event for those involved, but it also presents a great challenge to the forensic pathologist involved in the management of the surviving family members. Evaluation of families requires a multidisciplinary approach, which should include cardiologists, a clinical geneticist, a genetic counselor, and the forensic pathologist directly involved in the sudden death case. This multifaceted cardiac genetic service is crucial in the evaluation and management of the clinical, genetic, psychological, and social complexities observed in families in which there has been a young sudden cardiac death. The present study will address the spectrum of structural substrates of cardiac sudden death with particular emphasis given to the possible role of forensic molecular biology techniques in identifying subtle or even merely functional disorders accounting for electrical instability.

Impact of CPAP treatment on cardiac biomarkers and pro-BNP in obstructive sleep apnea syndrome.

PubMed

Cifçi, Nilüfer; Uyar, Meral; Elbek, Osman; Süyür, Hüseyin; Ekinci, Erhan

2010-09-01

To evaluate the effect of continuous positive airway pressure (CPAP) therapy on pro-brain natriuretic peptide (BNP) and cardiac markers in patients with obstructive sleep apnea syndrome and normal cardiac function. Thirty-three consecutive patients with sleep apnea syndrome were analysed for serum pro-BNP and cardiac markers prior to and after 6 months of CPAP therapy. Twenty five patients had normal (83.3%) while remaining five (16.7%) revealed high pro-BNP values. We did not detect any significant difference between severity of obstructive sleep apnea syndrome and serum pro-BNP levels (p = 0.534). A statistically significant difference was not observed between basal and sixth-month creatine kinase (CK), creatine kinase-MB (CK-MB), troponin I, pro-BNP, aspartate transaminase (AST), and CK levels in patients with sleep apnea syndrome (p > 0.05). Obstructive sleep apnea syndrome does not induce myocardial damage enough to increase serum pro-BNP, CK, CK-MB, troponin I, and AST levels. Markers sensitive to ischemia could be preferred to evaluate effect of obstructive sleep apnea syndrome.

Maternal hyperthyroidism increases the susceptibility of rat adult offspring to cardiovascular disorders.

PubMed

Lino, Caroline A; da Silva, Ivson Bezerra; Shibata, Caroline E R; Monteiro, Priscilla de S; Barreto-Chaves, Maria Luiza M

2015-11-15

Suboptimal intrauterine conditions as changed hormone levels during critical periods of the development are considered an insult and implicate in physiological adaptations which may result in pathological outcomes in later life. This study evaluated the effect of maternal hyperthyroidism (hyper) on cardiac function in adult offspring and the possible involvement of cardiac Renin-Angiotensin System (RAS) in this process. Wistar dams received orally thyroxin (12 mg/L) from gestational day 9 (GD9) until GD18. Adult offspring at postnatal day 90 (PND90) from hyper dams presented increased SBP evaluated by plethysmography and worse recovery after ischemia-reperfusion (I/R), as evidenced by decreased LVDP, +dP/dT and -dP/dT at 25 min of reperfusion and by increased infarct size. Increased cardiac Angiotensin I/II levels and AT1R in hyper offspring were verified. Herein, we provide evidences that maternal hyperthyroidism leads to altered expression of RAS components in adult offspring, which may be correlated with worse recovery of the cardiac performance after ischemic insults and hypertension. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Cardiac PET/CT for the Evaluation of Known or Suspected Coronary Artery Disease

PubMed Central

Murthy, Venkatesh L.

2011-01-01

Positron emission tomography (PET) is increasingly being applied in the evaluation of myocardial perfusion. Cardiac PET can be performed with an increasing variety of cyclotron- and generator-produced radiotracers. Compared with single photon emission computed tomography, PET offers lower radiation exposure, fewer artifacts, improved spatial resolution, and, most important, improved diagnostic performance. With its capacity to quantify rest–peak stress left ventricular systolic function as well as coronary flow reserve, PET is superior to other methods for the detection of multivessel coronary artery disease and, potentially, for risk stratification. Coronary artery calcium scoring may be included for further risk stratification in patients with normal perfusion imaging findings. Furthermore, PET allows quantification of absolute myocardial perfusion, which also carries substantial prognostic value. Hybrid PET–computed tomography scanners allow functional evaluation of myocardial perfusion combined with anatomic characterization of the epicardial coronary arteries, thereby offering great potential for both diagnosis and management. Additional studies to further validate the prognostic value and cost effectiveness of PET are warranted. © RSNA, 2011 PMID:21918042

ALDH2 protects against high fat diet-induced obesity cardiomyopathy and defective autophagy: role of CaM kinase II, histone H3K9 methyltransferase SUV39H, Sirt1, and PGC-1α deacetylation.

PubMed

Wang, Shuyi; Wang, Cong; Turdi, Subat; Richmond, Kacy L; Zhang, Yingmei; Ren, Jun

2018-06-01

Uncorrected obesity contributes to cardiac remodeling and contractile dysfunction although the underlying mechanism remains poorly understood. Mitochondrial aldehyde dehydrogenase (ALDH2) is a mitochondrial enzyme with some promises in a number of cardiovascular diseases. This study was designed to evaluate the impact of ALDH2 on cardiac remodeling and contractile property in high fat diet-induced obesity. Wild-type (WT) and ALDH2 transgenic mice were fed low (10% calorie from fat) or high (45% calorie from fat) fat diet for 5 months prior to the assessment of cardiac geometry and function using echocardiography, IonOptix system, Lectin, and Masson Trichrome staining. Western blot analysis was employed to evaluate autophagy, CaM kinase II, PGC-1α, histone H3K9 methyltransferase SUV39H, and Sirt-1. Our data revealed that high fat diet intake promoted weight gain, cardiac remodeling (hypertrophy and interstitial fibrosis, p < 0.0001) and contractile dysfunction (reduced fractional shortening (p < 0.0001), cardiomyocyte function (p < 0.0001), and intracellular Ca 2+ handling (p = 0.0346)), mitochondrial injury (elevated O 2 - levels, suppressed PGC-1α, and enhanced PGC-1α acetylation, p < 0.0001), elevated SUV39H, suppressed Sirt1, autophagy and phosphorylation of AMPK and CaM kinase II, the effects of which were negated by ALDH2 (p ≤ 0.0162). In vitro incubation of the ALDH2 activator Alda-1 rescued against palmitic acid-induced changes in cardiomyocyte function, the effect of which was nullified by the Sirt-1 inhibitor nicotinamide and the CaM kinase II inhibitor KN-93 (p < 0.0001). The SUV39H inhibitor chaetocin mimicked Alda-1-induced protection again palmitic acid (p < 0.0001). Examination in overweight human revealed an inverse correlation between diastolic cardiac function and ALDH2 gene mutation (p < 0.05). Taken together, these data suggest that ALDH2 serves as an indispensable factor against cardiac anomalies in diet-induced obesity through a mechanism related to autophagy regulation and facilitation of the SUV39H-Sirt1-dependent PGC-1α deacetylation.

Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?

PubMed

Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J

2016-12-01

The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

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.

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

PubMed

Greene, Stephen J; Epstein, Stephen E; Kim, Raymond J; Quyyumi, Arshed A; Cole, Robert T; Anderson, Allen S; Wilcox, Jane E; Skopicki, Hal A; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai I; Gheorghiade, Mihai; Butler, Javed

2017-04-01

This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance. This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion. This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

Deep breathing exercises with positive expiratory pressure at a higher rate improve oxygenation in the early period after cardiac surgery--a randomised controlled trial.

PubMed

Urell, Charlotte; Emtner, Margareta; Hedenström, Hans; Tenling, Arne; Breidenskog, Marie; Westerdahl, Elisabeth

2011-07-01

In addition to early mobilisation, a variety of breathing exercises are used to prevent postoperative pulmonary complications after cardiac surgery. The optimal duration of the treatment is not well evaluated. The aim of this study was to determine the effect of 30 versus 10 deep breaths hourly, while awake, with positive expiratory pressure on oxygenation and pulmonary function the first days after cardiac surgery. A total of 181 patients, undergoing cardiac surgery, were randomised into a treatment group, performing 30 deep breaths hourly the first postoperative days, or into a control group performing 10 deep breaths hourly. The main outcome measurement arterial blood gases and the secondary outcome pulmonary function, evaluated with spirometry, were determined on the second postoperative day. Preoperatively, both study groups were similar in terms of age, SpO(2), forced expiratory volume in 1s and New York Heart Association classification. On the second postoperative day, arterial oxygen tension (PaO(2)) was 8.9 ± 1.7 kPa in the treatment group and 8.1 ± 1.4 kPa in the control group (p = 0.004). Arterial oxygen saturation (SaO(2)) was 92.7 ± 3.7% in the treatment group and 91.1 ± 3.8% in the control group (p = 0.016). There were no differences in measured lung function between the groups or in compliance to the breathing exercises. Compliance was 65% of possible breathing sessions. A significantly increased oxygenation was found in patients performing 30 deep breaths the first two postoperative days compared with control patients performing 10 deep breaths hourly. These results support the implementation of a higher rate of deep breathing exercises in the initial phase after cardiac surgery. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: role of Sirt1-mediated autophagy regulation.

PubMed

Ren, Jun; Yang, Lifang; Zhu, Li; Xu, Xihui; Ceylan, Asli F; Guo, Wei; Yang, Jian; Zhang, Yingmei

2017-10-01

Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca 2+ properties were evaluated using echocardiography, IonOptix ® edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot. Our results revealed that Akt2 ablation prolonged life span (by 9.1%) and alleviated aging (24 months)-induced unfavorable changes in myocardial function and intracellular Ca 2+ handling (SERCA2a oxidation) albeit with more pronounced cardiac hypertrophy (58.1%, 47.8%, and 14.5% rises in heart weight, wall thickness, and cardiomyocyte cross-sectional area). Aging downregulated levels of Sirt1, increased phosphorylation of Akt, and the nuclear transcriptional factor Foxo1, as well as facilitated acetylation of Foxo1, the effects of which (except Sirt1 and Foxo1 acetylation) were significantly attenuated or negated by Akt2 ablation. Advanced aging disturbed autophagy, mitophagy, and mitochondrial integrity as evidenced by increased p62, decreased levels of beclin-1, Atg7, LC3B, BNIP3, PTEN-induced putative kinase 1 (PINK1), Parkin, UCP-2, PGC-1α, and aconitase activity, the effects of which were reversed by Akt2 ablation. Aging-induced cardiomyocyte contractile dysfunction and loss of mitophagy were improved by rapamycin and the Sirt1 activator SRT1720. Activation of Akt using insulin or Parkin deficiency prevented SRT1720-induced beneficial effects against aging. In conclusion, our data indicate that Akt2 ablation protects against cardiac aging through restored Foxo1-related autophagy and mitochondrial integrity. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

2D Echocardiographic Evaluation of Right Ventricular Function Correlates With 3D Volumetric Models in Cardiac Surgery Patients.

PubMed

Magunia, Harry; Schmid, Eckhard; Hilberath, Jan N; Häberle, Leo; Grasshoff, Christian; Schlensak, Christian; Rosenberger, Peter; Nowak-Machen, Martina

2017-04-01

The early diagnosis and treatment of right ventricular (RV) dysfunction are of critical importance in cardiac surgery patients and impact clinical outcome. Two-dimensional (2D) transesophageal echocardiography (TEE) can be used to evaluate RV function using surrogate parameters due to complex RV geometry. The aim of this study was to evaluate whether the commonly used visual evaluation of RV function and size using 2D TEE correlated with the calculated three-dimensional (3D) volumetric models of RV function. Retrospective study, single center, University Hospital. Seventy complete datasets were studied consisting of 2D 4-chamber view loops (2-3 beats) and the corresponding 4-chamber view 3D full-volume loop of the right ventricle. RV function and RV size of the 2D loops then were assessed retrospectively purely qualitatively individually by 4 clinician echocardiographers certified in perioperative TEE. Corresponding 3D volumetric models calculating RV ejection fraction and RV end-diastolic volumes then were established and compared with the 2D assessments. 2D assessment of RV function correlated with 3D volumetric calculations (Spearman's rho -0.5; p<0.0001). No correlation could be established between 2D estimates of RV size and actual 3D volumetric end-diastolic volumes (Spearman's rho 0.15; p = 0.25). The 2D assessment of right ventricular function based on visual estimation as frequently used in clinical practice appeared to be a reliable method of RV functional evaluation. However, 2D assessment of RV size seemed unreliable and should be used with caution. Copyright © 2017 Elsevier Inc. All rights reserved.

Using ballistocardiography to measure cardiac performance: a brief review of its history and future significance.

PubMed

Vogt, Emelie; MacQuarrie, David; Neary, John Patrick

2012-11-01

Ballistocardiography (BCG) is a non-invasive technology that has been used to record ultra-low-frequency vibrations of the heart allowing for the measurement of cardiac cycle events including timing and amplitudes of contraction. Recent developments in BCG have made this technology simple to use, as well as time- and cost-efficient in comparison with other more complicated and invasive techniques used to evaluate cardiac performance. Recent technological advances are considerably greater since the advent of microprocessors and laptop computers. Along with the history of BCG, this paper reviews the present and future potential benefits of using BCG to measure cardiac cycle events and its application to clinical and applied research. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism.

PubMed

Sun, Dan; Yang, Fei

2017-04-29

To investigate whether metformin can improve the cardiac function through improving the mitochondrial function in model of heart failure after myocardial infarction. Male C57/BL6 mice aged about 8 weeks were selected and the anterior descending branch was ligatured to establish the heart failure model after myocardial infarction. The cardiac function was evaluated via ultrasound after 3 days to determine the modeling was successful, and the mice were randomly divided into two groups. Saline group (Saline) received the intragastric administration of normal saline for 4 weeks, and metformin group (Met) received the intragastric administration of metformin for 4 weeks. At the same time, Shame group (Sham) was set up. Changes in cardiac function in mice were detected at 4 weeks after operation. Hearts were taken from mice after 4 weeks, and cell apoptosis in myocardial tissue was detected using TUNEL method; fresh mitochondria were taken and changes in oxygen consumption rate (OCR) and respiratory control rate (RCR) of mitochondria in each group were detected using bio-energy metabolism tester, and change in mitochondrial membrane potential (MMP) of myocardial tissue was detected via JC-1 staining; the expressions and changes in Bcl-2, Bax, Sirt3, PGC-1α and acetylated PGC-1α in myocardial tissue were detected by Western blot. RT-PCR was used to detect mRNA levels in Sirt3 in myocardial tissues. Metformin improved the systolic function of heart failure model rats after myocardial infarction and reduced the apoptosis of myocardial cells after myocardial infarction. Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1α in myocardial tissue of heart failure after myocardial infarction. Metformin decreases the acetylation level of PGC-1α through up-regulating Sirt3, mitigates the damage to mitochondrial membrane potential of model of heart failure after myocardial infarction and improves the respiratory function of mitochondria, thus improving the cardiac function of mice. Copyright © 2017. Published by Elsevier Inc.

Ultrasonographic Measures of Volume Responsiveness

DTIC Science & Technology

2017-02-01

variation, focused rapid echocardiographic evaluation , FREE, point-of-care ultrasound, POCUS, cardiac ultrasound 16. SECURITY CLASSIFICATION OF: 17...in small populations of medical patients on standard ventilator setting. There are very few studies directly comparing measures, or evaluating the...function are assessed as part of the FREE. Several predicative measures described below were assessed in the pre-TTE evaluation (Table 1). 4.2.1

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

PubMed

Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

2018-06-01

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

The usefulness of plasma asymmetric dimethylarginine (ADMA) levels and tissue doppler echocardiography for heart function in term infants born to mothers with gestational diabetes mellitus.

PubMed

Arslan, Derya; Oran, Bulent; Vatansev, Husamettin; Cimen, Derya; Guvenc, Osman

2013-11-01

The aim of this study was to examine whether asymmetric dimethylarginine (ADMA) concentrations are associated with ventricular function in the infants of mothers with gestational diabetes. Twenty-five term newborns of mothers with gestational diabetes and term newborns as the control group (n = 25) with normal general health status were evaluated at two time points, on the 3rd postnatal day, at the 3th months. Echocardiographic evaluations of all participants were performed and ADMA level was measured. In the first analysis, 10 patients (40%) had a septal thickness of 6 mm or more, indicating septal hypertrophy. In the first and second analysis, interventricular septum end-diastolic thickness (IVSTd) and the left ventricular posterior wall end-diastolic thickness (LVPWTd) in the patient group were higher than the control group. ADMA level measurement was not significantly different between the groups the first and second analysis. There was no difference in ADMA levels of the group with septal thickness ≥6 mm and the group with <6 mm. Newborn cardiac wall thickness was increased in pregnancies complicated by Gestational diabetes mellitus (GDM), and the increase was independent of glycemic control. Diastolic newborn cardiac function was impaired in GDM, and this effect was independent of septal thickness. We found no association between ADMA levels and cardiac systolic, diastolic functions or septum thickness in the GDM newborn.

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.

Effect of L-Carnitine Supplementation on Apelin and Apelin Receptor (Apj) Expression in Cardiac Muscle of Obese Diabetic Rats.

PubMed

Ranjbar Kohan, Neda; Nazifi, Saeed; Tabandeh, Mohammad Reza; Ansari Lari, Maryam

2018-10-01

L-carnitine (LC) has been shown to protect cardiac metabolism in diabetes patients with cardiovascular diseases (CVDs). Apelin, a newly discovered adipocytokines, is an important regulator of cardiac muscle function; however, the role of the level of expression of Apelin axis in improvement of cardiac function by LC in diabetic patients, is not clear. In the present study, obese insulin-resistant rats were used to determine the effect of LC, when given orally with a high-calorie diet, on Apelin and Apelin receptor (Apj) expression in cardiac muscle. In this experimental study, rats were fed with high-fat/high-carbohydrate diet for five weeks and subsequently were injected with streptozotocin 30 mg/kg for induction of obesity and insulin resistance. After confirming the induction of diabetes (serum glucose above 7.5 mmol/L), the animals received LC 300 mg/kg in drinking water for 28 days. On days 0, 14 and 28 after treatment, cardiac Apelin and Apj gene expression was evaluated by real time polymerase chain reaction (PCR) analysis. Serum levels of insulin, Apelin, glucose, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and the homeostasis model assessment of insulin resistance (HOMA-IR) were also measured using commercial kits. Cardiac Apelin and Apj expression and serum Apelin were increased in obese rats, while LC supplementation decreased the serum levels of Apelin and down-regulated Apelin and Apj expression in cardiac muscle. These changes were associated with reduced insulin resistance markers and serum inflammatory factors and improved lipid profile. We concluded that LC supplementation could attenuate the over-expression of Apelin axis in heart of diabetic rats, a novel mechanism by which LC improves cardiovascular complications in diabetic patients. Copyright© by Royan Institute. All rights reserved.

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights from Simultaneous Cardio-Neural Mapping

PubMed Central

Hamon, David; Rajendran, Pradeep S.; Chui, Ray W.; Ajijola, Olujimi A.; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S.; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

2017-01-01

Background Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system (ICNS), a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on ICNS function in generating cardiac neuronal and electrical instability using a novel cardio-neural mapping approach. Methods and Results In a porcine model (n=8) neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared to fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electrical instability was also observed following variable (short) CI PVCs. Conclusions Variable CI PVCs affect critical populations of ICNS neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling leading to cardiomyopathy. PMID:28408652

Left Ventricular Endocardium Tracking by Fusion of Biomechanical and Deformable Models

PubMed Central

Gu, Jason

2014-01-01

This paper presents a framework for tracking left ventricular (LV) endocardium through 2D echocardiography image sequence. The framework is based on fusion of biomechanical (BM) model of the heart with the parametric deformable model. The BM model constitutive equation consists of passive and active strain energy functions. The deformations of the LV are obtained by solving the constitutive equations using ABAQUS FEM in each frame in the cardiac cycle. The strain energy functions are defined in two user subroutines for active and passive phases. Average fusion technique is used to fuse the BM and deformable model contours. Experimental results are conducted to verify the detected contours and the results are evaluated by comparing themto a created gold standard. The results and the evaluation proved that the framework has the tremendous potential to track and segment the LV through the whole cardiac cycle. PMID:24587814

Imaging and Modeling of Myocardial Metabolism

PubMed Central

Jamshidi, Neema; Karimi, Afshin; Birgersdotter-Green, Ulrika; Hoh, Carl

2010-01-01

Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed. PMID:20559785

Myocardial Adeno-Associated Virus Serotype 6–βARKct Gene Therapy Improves Cardiac Function and Normalizes the Neurohormonal Axis in Chronic Heart Failure

PubMed Central

Rengo, Giuseppe; Lymperopoulos, Anastasios; Zincarelli, Carmela; Donniacuo, Maria; Soltys, Stephen; Rabinowitz, Joseph E.; Koch, Walter J.

2009-01-01

Background The upregulation of G protein–coupled receptor kinase 2 in failing myocardium appears to contribute to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function. The peptide βARKct, which can inhibit the activation of G protein–coupled receptor kinase 2 and improve βAR signaling, has been shown in transgenic models and short-term gene transfer experiments to rescue heart failure (HF). This study was designed to evaluate long-term βARKct expression in HF with the use of stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). Methods and Results In HF rats, we delivered βARKct or green fluorescent protein as a control via AAV6-mediated direct intramyocardial injection. We also treated groups with concurrent administration of the β-blocker metoprolol. We found robust and long-term transgene expression in the left ventricle at least 12 weeks after delivery. βARKct significantly improved cardiac contractility and reversed left ventricular remodeling, which was accompanied by a normalization of the neurohormonal (catecholamines and aldosterone) status of the chronic HF animals, including normalization of cardiac βAR signaling. Addition of metoprolol neither enhanced nor decreased βARKct-mediated beneficial effects, although metoprolol alone, despite not improving contractility, prevented further deterioration of the left ventricle. Conclusions Long-term cardiac AAV6-βARKct gene therapy in HF results in sustained improvement of global cardiac function and reversal of remodeling at least in part as a result of a normalization of the neurohormonal signaling axis. In addition, βARKct alone improves outcomes more than a β-blocker alone, whereas both treatments are compatible. These findings show that βARKct gene therapy can be of long-term therapeutic value in HF. PMID:19103992

Cardio-hepatic risk assessment by CMR imaging in liver transplant candidates.

PubMed

Reddy, Sahadev T; Thai, Ngoc L; Oliva, Jose; Tom, Kusum B; Dishart, Michael K; Doyle, Mark; Yamrozik, June A; Williams, Ronald B; Shah, Moneal; Wani, Adil; Singh, Anil; Maheswary, Rishi; Biederman, Robert W W

2018-03-02

The preoperative workup of orthotopic liver transplantation (OLT) patients is practically complex given the need for multiple imaging modalities. We recently demonstrated in our proof-of-concept study the value of a one-stop-shop approach using cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of hepatocellular carcinoma (HCC) as well as cardiovascular risk assessment is critically important in these patients. We hypothesized that coronary risk assessment and HCC detectability is acceptable using the one-stop-shop CMR approach. In this observational study, patients underwent CMRI evaluation including cardiac function, stress CMR, thoracoabdominal MRA, and abdominal MRI on a standard MRI scanner in one examination. Over 8 years, 252 OLT candidates underwent evaluation in the cardiac MRI suit. The completion rates for each segment of the CMR examination were 99% for function, 95% completed stress CMR, 93% completed LGE for viability, 85% for liver MRI, and 87% for MRA. A negative CMR stress examination had 100% CAD event-free survival at 12 months. A total of 63 (29%) patients proceeded to OLT. Explant pathology confirmed detection/exclusion of HCC. This study further defines the population suitable for the one-stop-shop CMR concept for preop evaluation of OLT candidates providing a road map for integrated testing in this complex patient population for evaluation of cardiac risk and detection of HCC lesions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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 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.

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.

Influence of acid functionalization on the cardiopulmonary toxicity of carbon nanotubes and carbon black particles in mice

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

Tong Haiyan; McGee, John K.; Saxena, Rajiv K.

2009-09-15

Engineered carbon nanotubes are being developed for a wide range of industrial and medical applications. Because of their unique properties, nanotubes can impose potentially toxic effects, particularly if they have been modified to express functionally reactive chemical groups on their surface. The present study was designed to evaluate whether acid functionalization (AF) enhanced the cardiopulmonary toxicity of single-walled carbon nanotubes (SWCNT) as well as control carbon black particles. Mice were exposed by oropharyngeal aspiration to 10 or 40 {mu}g of saline-suspended single-walled carbon nanotubes (SWCNTs), acid-functionalized SWCNTs (AF-SWCNTs), ultrafine carbon black (UFCB), AF-UFCB, or 2 {mu}g LPS. 24 hours later,more » pulmonary inflammatory responses and cardiac effects were assessed by bronchoalveolar lavage and isolated cardiac perfusion respectively, and compared to saline or LPS-instilled animals. Additional mice were assessed for histological changes in lung and heart. Instillation of 40 {mu}g of AF-SWCNTs, UFCB and AF-UFCB increased percentage of pulmonary neutrophils. No significant effects were observed at the lower particle concentration. Sporadic clumps of particles from each treatment group were observed in the small airways and interstitial areas of the lungs according to particle dose. Patches of cellular infiltration and edema in both the small airways and in the interstitium were also observed in the high dose group. Isolated perfused hearts from mice exposed to 40 {mu}g of AF-SWCNTs had significantly lower cardiac functional recovery, greater infarct size, and higher coronary flow rate than other particle-exposed animals and controls, and also exhibited signs of focal cardiac myofiber degeneration. No particles were detected in heart tissue under light microscopy. This study indicates that while acid functionalization increases the pulmonary toxicity of both UFCB and SWCNTs, this treatment caused cardiac effects only with the AF-carbon nanotubes. Further experiments are needed to understand the physico-chemical processes involved in this phenomenon.« less

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.

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

Reduced aspirin responsiveness as assessed by impedance aggregometry is not associated with adverse outcome after cardiac surgery in a small low-risk cohort.

PubMed

Bolliger, Daniel; Filipovic, Miodrag; Matt, Peter; Tanaka, Kenichi A; Gregor, Michael; Zenklusen, Urs; Seeberger, Manfred D; Lurati Buse, Giovanna

2016-01-01

Reduced aspirin responsiveness (i.e. persistent high platelet reactivity in platelet function testing) might be associated with increased risk of myocardial ischemia and cardiac mortality in patients with coronary disease. However, the impact in patients undergoing coronary artery bypass grafting (CABG) is unclear. The aim of this prospective cohort study was to evaluate the predictive value of reduced aspirin responsiveness on cardiac and thromboembolic events in patients undergoing elective isolated CABG surgery with aspirin intake until at least two days before surgery. We included 304 patients in this prospective single-center cohort study. Impedance platelet aggregometry (Multiplate®) was performed directly before and on the first day after surgery. Reduced aspirin responsiveness was defined as area under the curve in ASPItest (AUCASPI) ≥300 U. The primary outcome was a composite of all-cause mortality and/or major adverse cardiac or thromboembolic events within 1 year. Reduced aspirin responsiveness was found in 13 and 24% of patients pre and postoperatively, respectively. There was no difference in the outcomes between patients with normal and reduced aspirin responsiveness in the preoperative measurement (log-rank test, p = 0.540). Multivariate analysis including logistic EuroSCORE I and postoperative troponin T levels did not show any association of reduced aspirin responsiveness with adverse outcome (hazard ratio, 0.576; (95% CI 0.128-2.585; p = 0.471). Similarly, postoperative reduced aspirin responsiveness was not associated with adverse events. To conclude, reduced aspirin responsiveness as evaluated by Multiplate® platelet function analyzer was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery.

A prospective study on the impact of heart rate control achieved with metoprolol on cardiac performance, motor function and quality of life in Chinese chronic heart failure patients.

PubMed

Meng, Yong; Liu, Xuelu; Liu, Juan; Cheng, Xianliang

2017-01-15

To prospectively evaluate the impact of metoprolol achieved heart rate (HR) on cardiac-motor function and quality of life (QoL) in chronic heart failure (CHF) patients. Between February 2013 to April 2016, association of HR reduction with haemodynamic indices, motor function and QoL in CHF patients with HR>80bpm receiving metoprolol 23.75mg or 47.5mgq.d was studied. Overall, 154 patients (median age, 66.39years; males, n=101; females, n=53) were enrolled, whose average resting HR decreased significantly from baseline value of 82.72±6.73 to 69.38±3.57, 67.72±2.61, 66.50±3.14 and 64.86±3.21bpm in the 1st, 3rd, 6th and 12th months post metoprolol intervention, respectively (P<0.0001). Similarly, the ejection fraction (r=-0.6461, P<0.0001), cardiac output (r=-0.5238, P<0.0001), cardiac index (r=-0.5378, P<0.0001) and veterans specific activity questionnaire scores (r=-0.4088, P<0.0001) were significantly associated with the reduction in HR after 12months. The improvement in 6-min walk test was independent of HR reduction (P=0.005). Similarly, QoL as measured by short form-8 questionnaire (SF-8) but not Minnesota Living with Heart Failure was significantly improved at the 12th-month. However, this was not associated with the reductions in HR. Metoprolol achieved HR control was associated with improvement in cardiac performance and motor function but not QoL in patients with CHF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Adaptive servo-ventilation for central sleep apnoea in systolic heart failure: results of the major substudy of SERVE-HF.

PubMed

Cowie, Martin R; Woehrle, Holger; Wegscheider, Karl; Vettorazzi, Eik; Lezius, Susanne; Koenig, Wolfgang; Weidemann, Frank; Smith, Gillian; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita K; Somers, Virend K; Zannad, Faiez; Teschler, Helmut

2018-03-01

The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers. In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months. In secondary analyses, data for patients with baseline and 12-month values were evaluated; 312 patients participated in the substudy. The primary endpoint, change in echocardiographically determined left ventricular ejection fraction from baseline to 12 months, did not differ significantly between the ASV and the control groups. There were also no significant between-group differences for changes in left ventricular dimensions, wall thickness, diastolic function or right ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in small patient numbers). Plasma N-terminal pro B-type natriuretic peptide concentration decreased in both groups, and values were similar at 12 months. There were no significant between-group differences in changes in cardiac, renal and systemic inflammation biomarkers. In patients with systolic heart failure and CSA, addition of ASV to guideline-based medical management had no statistically significant effect on cardiac structure and function, or on cardiac biomarkers, renal function and systemic inflammation over 12 months. The increased cardiovascular mortality reported in SERVE-HF may not be related to adverse remodelling or worsening heart failure. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

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

Ledee, Dolena R.; Smith, Lincoln; Kajimoto, Masaki

Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of glycolytic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin. Western blots were used to evaluate metabolic enzymes. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (presumably glucose) contribution. Myc inactivation (MycKO-TAC) inhibited these metabolic changes. Hypertrophy in general increased protein levels of PKM2; however this change was not linked to Myc status. Protein post-translation modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. In conclusion, Myc regulates substrate utilization during early pressure overload hypertrophy. Our results show that the metabolic switch during hypertrophy is not necessary to maintain cardiac function, but it may be important mechanism to promote cardiomyocyte growth. Myc also regulates protein O-GlcNAcylation during hypertrophy.« less

Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study

PubMed Central

Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

2014-01-01

Background: Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. Objectives: The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Methods: Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism. Results: Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Conclusion: Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism. PMID:25093618

Myocardial Autophagy after Severe Burn in Rats

PubMed Central

Zhang, Qiong; Shi, Xiao-hua; Huang, Yue-sheng

2012-01-01

Background Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn. Methods Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function. Results Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 ± 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 ± 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite response. Enalaprilat, losartan, and DPI all inhibited autophagy and enhanced heart function. Conclusion Myocardial autophagy is enhanced in severe burns and autophagic cell death occurred early at 3 h post-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important roles in this process by regulating cell signaling transduction. PMID:22768082

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.

Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

PubMed Central

Xie, Jun; He, Guixin; Chen, Qinhua; Sun, Jiayin; Dai, Qin; Lu, Jianrong; Li, Guannan; Wu, Han; Li, Ran; Chen, Jianzhou; Xu, Wei; Xu, Biao

2016-01-01

Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4–/–) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4–/– compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy. PMID:26835698

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model.

PubMed

Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio

2016-07-16

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.

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.

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.

[Myocardial viability: update in nuclear cardiology].

PubMed

Vallejo, Enrique

2007-01-01

Evaluation of myocardial viability with the aid of radionuclides, is a technique that offers reliable, reproducible information, with an attractive cost-benefit relationship, in the study of the myocardial viability, integrating cardiac molecular, metabolic, and functional aspects. Nowadays, coronary risk stratification in post-myocardial infarction patients pretends to locate them as low-, intermediate, and high risk-subjects that can suffer cardiovascular complications in the very near future. Low-risk patients are characterized by a cardiac-related mortality below 1%, whereas high-risk mortality is greater than 3%. Because of clinical complications following a myocardial infarction are observed during the first month of evolution, clinical guidelines suggest to evaluate the cardiovascular risk before hospital discharge.

Cardiac Magnetic Resonance-Verified Myocardial Fibrosis in Chagas Disease: Clinical Correlates and Risk Stratification

PubMed Central

Uellendahl, Marly; de Siqueira, Maria Eduarda Menezes; Calado, Eveline Barros; Kalil-Filho, Roberto; Sobral, Dário; Ribeiro, Clébia; Oliveira, Wilson; Martins, Silvia; Narula, Jagat; Rochitte, Carlos Eduardo

2016-01-01

Background Chagas disease (CD) is an important cause of heart failure and mortality, mainly in Latin America. This study evaluated the morphological and functional characteristics of the heart as well the extent of myocardial fibrosis (MF) in patients with CD by cardiac magnetic resonance (CMR). The prognostic value of MF evaluated by myocardial-delayed enhancement (MDE) was compared with that via Rassi score. Methods This study assessed 39 patients divided into 2 groups: 28 asymptomatic patients as indeterminate form group (IND); and symptomatic patients as Chagas Heart Disease (CHD) group. All patients underwent CMR using the techniques of cine-MRI and MDE, and the amount of MF was compared with the Rassi score. Results Regarding the morphological and functional analysis, significant differences were observed between both groups (p < 0.001). Furthermore, there was a strong correlation between the extent of MF and the Rassi score (r = 0.76). Conclusions CMR is an important technique for evaluating patients with CD, stressing morphological and functional differences in all clinical presentations. The strong correlation with the Rassi score and the extent of MF detected by CMR emphasizes its role in the prognostic stratification of patients with CD. PMID:27982271

Left Ventricular Assist Device as a Bridge to Recovery for Patients With Advanced Heart Failure.

PubMed

Jakovljevic, Djordje G; Yacoub, Magdi H; Schueler, Stephan; MacGowan, Guy A; Velicki, Lazar; Seferovic, Petar M; Hothi, Sandeep; Tzeng, Bing-Hsiean; Brodie, David A; Birks, Emma; Tan, Lip-Bun

2017-04-18

Left ventricular assist devices (LVADs) have been used as an effective therapeutic option in patients with advanced heart failure, either as a bridge to transplantation, as destination therapy, or in some patients, as a bridge to recovery. This study evaluated whether patients undergoing an LVAD bridge-to-recovery protocol can achieve cardiac and physical functional capacities equivalent to those of healthy controls. Fifty-eight male patients-18 implanted with a continuous-flow LVAD, 16 patients with LVAD explanted (recovered patients), and 24 heart transplant candidates (HTx)-and 97 healthy controls performed a maximal graded cardiopulmonary exercise test with continuous measurements of respiratory gas exchange and noninvasive (rebreathing) hemodynamic data. Cardiac function was represented by peak exercise cardiac power output (mean arterial blood pressure × cardiac output) and functional capacity by peak exercise O 2 consumption. All patients demonstrated a significant exertional effort as demonstrated with the mean peak exercise respiratory exchange ratio >1.10. Peak exercise cardiac power output was significantly higher in healthy controls and explanted LVAD patients compared with other patients (healthy 5.35 ± 0.95 W; explanted 3.45 ± 0.72 W; LVAD implanted 2.37 ± 0.68 W; and HTx 1.31 ± 0.31 W; p < 0.05), as was peak O 2 consumption (healthy 36.4 ± 10.3 ml/kg/min; explanted 29.8 ± 5.9 ml/kg/min; implanted 20.5 ± 4.3 ml/kg/min; and HTx 12.0 ± 2.2 ml/kg/min; p < 0.05). In the LVAD explanted group, 38% of the patients achieved peak cardiac power output and 69% achieved peak O 2 consumption within the ranges of healthy controls. The authors have shown that a substantial number of patients who recovered sufficiently to allow explantation of their LVAD can even achieve cardiac and physical functional capacities nearly equivalent to those of healthy controls. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality.

PubMed

Jorge, Luciana; Rodrigues, Bruno; Rosa, Kaleizu Teodoro; Malfitano, Christiane; Loureiro, Tatiana Carolina Alba; Medeiros, Alessandra; Curi, Rui; Brum, Patricia Chakur; Lacchini, Silvia; Montano, Nicola; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2011-04-01

To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO(2) max). Left ventricular function was evaluated non-invasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 ± 6%) compared with SI (34 ± 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.

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.

IFATS Collection: Human Adipose Tissue-Derived Stem Cells Induce Angiogenesis and Nerve Sprouting Following Myocardial Infarction, in Conjunction with Potent Preservation of Cardiac Function

PubMed Central

Cai, Liying; Johnstone, Brian H.; Cook, Todd G.; Tan, Jian; Fishbein, Michael C.; Chen, Peng-Sheng; March, Keith L.

2010-01-01

The administration of therapeutic cell types, such as stem and progenitor cells, has gained much interest for the limitation or repair of tissue damage caused by a variety of insults. However, it is still uncertain whether the morphological and functional benefits are mediated predominantly via cell differentiation or paracrine mechanisms. Here, we assessed the extent and mechanisms of adipose-derived stromal/stem cells (ASC)-dependent tissue repair in the context of acute myocardial infarction. Human ASCs in saline or saline alone was injected into the peri-infarct region in athymic rats following left anterior descending (LAD) coronary artery ligation. Cardiac function and structure were evaluated by serial echocardiography and histology. ASC-treated rats consistently exhibited better cardiac function, by all measures, than control rats 1 month following LAD occlusion. Left ventricular (LV) ejection fraction and fractional shortening were improved in the ASC group, whereas LV remodeling and dilation were limited in the ASC group compared with the saline control group. Anterior wall thinning was also attenuated by ASC treatment, and post-mortem histological analysis demonstrated reduced fibrosis in ASC-treated hearts, as well as increased peri-infarct density of both arterioles and nerve sprouts. Human ASCs were persistent at 1 month in the peri-infarct region, but they were not observed to exhibit significant cardiomyocyte differentiation. Human ASCs preserve heart function and augment local angiogenesis and cardiac nerve sprouting following myocardial infarction predominantly by the provision of beneficial trophic factors. PMID:18772313

Irradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature.

PubMed

Seemann, Ingar; Gabriels, Karen; Visser, Nils L; Hoving, Saske; te Poele, Johannes A; Pol, Jeffrey F; Gijbels, Marion J; Janssen, Ben J; van Leeuwen, Fijs W; Daemen, Mat J; Heeneman, Sylvia; Stewart, Fiona A

2012-05-01

Radiotherapy of thoracic and chest wall tumors increases the long-term risk of cardiotoxicity, but the underlying mechanisms are unclear. Single doses of 2, 8, or 16 Gy were delivered to the hearts of mice and damage was evaluated at 20, 40, and 60 weeks, relative to age matched controls. Single photon emission computed tomography (SPECT/CT) and ultrasound were used to measure cardiac geometry and function, which was related to histo-morphology and microvascular damage. Gated SPECT/CT and ultrasound demonstrated decreases in end diastolic and systolic volumes, while the ejection fraction was increased at 20 and 40 weeks after 2, 8, and 16 Gy. Cardiac blood volume was decreased at 20 and 60 weeks after irradiation. Histological examination revealed inflammatory changes at 20 and 40 weeks after 8 and 16 Gy. Microvascular density in the left ventricle was decreased at 40 and 60 weeks after 8 and 16 Gy, with functional damage to remaining microvasculature manifest as decreased alkaline phosphatase (2, 8, and 16 Gy), increased von Willebrand Factor and albumin leakage from vessels (8 and 16 Gy), and amyloidosis (16 Gy). 16 Gy lead to sudden death between 30 and 40 weeks in 38% of mice. Irradiation with 2 and 8 Gy induced modest changes in murine cardiac function within 20 weeks but this did not deteriorate further, despite progressive structural and microvascular damage. This indicates that heart function can compensate for significant structural damage, although higher doses, eventually lead to sudden death. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Current trends in cardiac rehabilitation

PubMed Central

Dafoe, W; Huston, P

1997-01-01

Cardiac rehabilitation can reduce mortality and morbidity for patients with many types of cardiac disease cost-effectively, yet is generally underutilized. Rehabilitation is helpful not only for patients who have had a myocardial infarction but also for those with stable angina or congestive heart failure or those who have undergone myocardial revascularization procedures, a heart transplant or heart valve surgery. The beneficial effects of rehabilitation include a reduction in the rate of death from cardiovascular disease, improved exercise tolerance, fewer cardiac symptoms, improved lipid levels, decreased cigarette smoking, improvement in psychosocial well-being and increased likelihood of return to work. Rehabilitation involves a multidisciplinary team that focuses on education, individually tailored exercise, risk-factor modification and the optimization of functional status and mental health. Current research trends in this area include the evaluation of new secondary-prevention modalities and alternative program options, such as home-based rehabilitation. PMID:9054823

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.

Electroactive polyurethane/siloxane derived from castor oil as a versatile cardiac patch, part I: Synthesis, characterization, and myoblast proliferation and differentiation.

PubMed

Baheiraei, Nafiseh; Gharibi, Reza; Yeganeh, Hamid; Miragoli, Michele; Salvarani, Nicolò; Di Pasquale, Elisa; Condorelli, Gianluigi

2016-03-01

Tissue-engineered cardiac patch aims at regenerating an infarcted heart by improving cardiac function and providing mechanical support to the diseased myocardium. In order to take advantages of electroactivity, a new synthetic method was developed for the introduction of an electroactive oligoaniline into the backbone of prepared patches. For this purpose, a series of electroactive polyurethane/siloxane films containing aniline tetramer (AT) was prepared through sol-gel reaction of trimethoxysilane functional intermediate polyurethane prepolymers made from castor oil and poly(ethylene glycol). Physicochemical, mechanical, and electrical conductivity of samples were evaluated and the recorded results were correlated to their structural characteristics. The optimized films were proved to be biodegradable and have tensile properties suitable for cardiac patch application. The embedded AT moieties in the backbone of the prepared samples preserved their electroactivity with the electrical conductivity in the range of 10 -4 S/cm. The prepared films were compatible with proliferation of C2C12 and had potential for enhancing myotube formation even without external electrical stimulation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 775-787, 2016. © 2015 Wiley Periodicals, Inc.

Transplantation of marrow-derived cardiac stem cells carried in fibrin improves cardiac function after myocardial infarction.

PubMed

Guo, Hai-Dong; Wang, Hai-Jie; Tan, Yu-Zhen; Wu, Jin-Hong

2011-01-01

The high death rate of the transplanted stem cells in the infarcted heart and the low efficiency of differentiation toward cardiomyocytes influence the outcome of stem cell transplantation for treatment of myocardial infarction (MI). Fibrin glue (FG) has been extensively used as a cell implantation matrix to increase cell survival. However, mechanisms of the effects of FG for stem cell transplantation to improve cardiac function are unclear. We have isolated c-kit+/Sca-1+ marrow-derived cardiac stem cells (MCSCs) from rat bone marrow; the cells expressed weakly early cardiac transcription factor Nkx2.5, GATA-4, Mef2C, and Tbx5. Effects of FG on survival, proliferation, and migration of MCSCs were examined in vitro. Cytoprotective effects of FG were assessed by exposure of MCSCs to anoxia. Efficacy of MCSC transplantation in FG was evaluated in the female rat MI model. The MCSCs survived well and proliferated in FG, and they may migrate out from the edge of FG in the wound and nature state. Acridine orange/ethidium bromide staining and lactate dehydrogenase analysis showed that MCSCs in FG were more resistant to anoxia as compared with MCSCs alone. In a rat MI model, cardiac function was improved and scar area was obviously reduced in group of MCSCs in FG compared with group of MCSCs and FG alone, respectively. Y chromosome fluorescence in situ hybridization showed that there were more survived MCSCs in group of MCSCs in FG than those in group of MCSCs alone, and most Y chromosome positive cells expressed cardiac troponin T (cTnT) and connexin-43 (Cx-43). Cx-43 was located between Y chromosome positive cells and recipient cardiomyocytes. Microvessel density in the peri-infarct regions and infarct regions significantly increased in group of MCSCs in FG. These results suggest that FG provide a suitable microenvironment for survival and proliferation of MCSCs and protect cells from apoptosis and necrosis caused by anoxia. MCSCs could differentiate into cardiomyocytes after being transplanted in the border of the infarcted myocardium and form connections with native cardiomyocytes. FG is helpful for MCSC transplantation to repair myocardium and improve cardiac function through promoting the survival, migration, and cardiomyogenic differentiation of MCSCs and inducing angiogenesis.

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.

LncRNA ZFAS1 as a SERCA2a Inhibitor to Cause Intracellular Ca2+ Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction.

PubMed

Zhang, Ying; Jiao, Lei; Sun, Lihua; Li, Yanru; Gao, Yuqiu; Xu, Chaoqian; Shao, Yingchun; Li, Mengmeng; Li, Chunyan; Lu, Yanjie; Pan, Zhenwei; Xuan, Lina; Zhang, Yiyuan; Li, Qingqi; Yang, Rui; Zhuang, Yuting; Zhang, Yong; Yang, Baofeng

2018-05-11

Ca 2+ homeostasis-a critical determinant of cardiac contractile function-is critically regulated by SERCA2a (sarcoplasmic reticulum Ca 2+ -ATPase 2a). Our previous study has identified ZFAS1 as a new lncRNA biomarker of acute myocardial infarction (MI). To evaluate the effects of ZFAS1 on SERCA2a and the associated Ca 2+ homeostasis and cardiac contractile function in the setting of MI. ZFAS1 expression was robustly increased in cytoplasm and sarcoplasmic reticulum in a mouse model of MI and a cellular model of hypoxia. Knockdown of endogenous ZFAS1 by virus-mediated silencing shRNA partially abrogated the ischemia-induced contractile dysfunction. Overexpression of ZFAS1 in otherwise normal mice created similar impairment of cardiac function as that observed in MI mice. Moreover, at the cellular level, ZFAS1 overexpression weakened the contractility of cardiac muscles. At the subcellular level, ZFAS1 deleteriously altered the Ca 2+ transient leading to intracellular Ca 2+ overload in cardiomyocytes. At the molecular level, ZFAS1 was found to directly bind SERCA2a protein and to limit its activity, as well as to repress its expression. The effects of ZFAS1 were readily reversible on knockdown of this lncRNA. Notably, a sequence domain of ZFAS1 gene that is conserved across species mimicked the effects of the full-length ZFAS1 . Mutation of this domain or application of an antisense fragment to this conserved region efficiently canceled out the deleterious actions of ZFAS1 . ZFAS1 had no significant effects on other Ca 2+ -handling regulatory proteins. ZFAS1 is an endogenous SERCA2a inhibitor, acting by binding to SERCA2a protein to limit its intracellular level and inhibit its activity, and a contributor to the impairment of cardiac contractile function in MI. Therefore, anti- ZFAS1 might be considered as a new therapeutic strategy for preserving SERCA2a activity and cardiac function under pathological conditions of the heart. © 2018 The Authors.

Qiliqiangxin inhibits the development of cardiac hypertrophy, remodeling, and dysfunction during 4 weeks of pressure overload in mice.

PubMed

Zou, Yunzeng; Lin, Li; Ye, Yong; Wei, Jianming; Zhou, Ning; Liang, Yanyan; Gong, Hui; Li, Lei; Wu, Jian; Li, Yunbo; Jia, Zhenhua; Wu, Yiling; Zhou, Jingmin; Ge, Junbo

2012-03-01

Qiliqiangxin (QL), a traditional Chinese medicine, has been used in the treatment of chronic heart failure. However, whether QL can benefit cardiac remodeling in the hypertensive state is unknown. We here examined the effects of QL on the development of cardiac hypertrophy through comparing those of losartan in C57BL/6 mice underlying transverse aorta constriction for 4 weeks. QL and losartan were administrated at 0.6 mg and 13.4 mg·kg·d, respectively. Cardiac hypertrophy, function, and remodeling were evaluated by echocardiography, catheterization, histology, and examination of specific gene expression and ERK phosphorylation. Cardiac apoptosis, autophagy, tumor necrosis factor α/insulin-like growth factor-1, and angiotensin II type 1 receptor expression and especially the proliferation of cardiomyocytes and phosphorylation of ErbB receptors were examined in vivo to elucidate the mechanisms. Transverse aorta constriction for 2 weeks resulted in a significant cardiac hypertrophy, which was significantly suppressed by either QL or losartan treatment. At 4 weeks after transverse aorta constriction, although the development of cardiac dysfunction and remodeling and the increases in apoptosis, autophagy, tumor necrosis factor α/insulin-like growth factor-1, and angiotensin II type 1 receptor expression were abrogated comparably between QL and losartan treatments, QL, but not losartan, enhanced proliferation of cardiomyocytes, which was paralleled with dowregulation of CCAAT/enhancer-binding protein β, upregulation of CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4, and increases in ErbB2 and ErbB4 phosphorylation. Furthermore, inhibition of either ErbB2 or CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4 abolished the cardiac protective effects of QL. Thus, QL inhibits myocardial inflammation and cardiomyocyte death and promotes cardiomyocyte proliferation, leading to an ameliorated cardiac remodeling and function in a mouse model of pressure overload. The possible mechanisms may involve inhibition of angiotensin II type 1 receptor and activation of ErbB receptors.

Isolated, broad-based apical diverticulum: cardiac magnetic resonance is a "terminator" of cardiac imaging modality for the evaluation of cardiac apex.

PubMed

Ahn, Hyo-Suk; Kim, Hyung-Kwan; Park, Eun-Ah; Lee, Whal; Park, Jae-Hyung; Sohn, Dae-Won

2013-10-01

In spite of the frequent involvement of many cardiac diseases, it is difficult to evaluate the left ventricular apex in detail with transthoracic echocardiography, a first-line imaging modality in cardiovascular diseases, because the apex is very closely located at the echocardiographic probe. Cardiac magnetic resonance enables us to evaluate the cardiac apex without any limitation to the image acquisition. We here present a case regarding a broad-based apical diverticulum, which was initially confused with apical aneurysm.

Haemodynamic Changes During Anaesthesia in the Prone Position, Evaluated Using Transoesophageal Ultrasound

ClinicalTrials.gov

2015-11-02

Obesity; Spinal Surgery; Anaesthesia; Changes in Left and Right Ventricle Dimension; Changes in Bloodflow Across Cardiac Valves; Changes in Dimensions of Inferior Caval Dimension and Hepatic Venous Bloodflow; Changes i Myocardial Velocities; Changes in Diastolic Function

Inhalation of Simulated Smog Affects Cardiac Function in Mice

EPA Science Inventory

Rationale: The health effects of individual criteria air pollutants have been well investigated. Little is known about health effects of inhaled multi-pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the card...

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.

The Effect of Tonsillectomy and Adenoidectomy on Right Ventricle Function and Pulmonary Artery Pressure by Using Doppler Echocardiography in Children.

PubMed

Acar, Onur Çağlar; Üner, Abdurrahman; Garça, Mehmet Fatih; Ece, İbrahim; Epçaçan, Serdar; Turan, Mahfuz; Kalkan, Ferhat

2016-06-01

The purpose of the present study is to emphasize the efficacy of the myocardial performance index and tricuspid annular plane systolic excursion (TAPSE) in the determination of impaired cardiac functions and recovery period following the treatment in children with adenoid and/or tonsillar hypertrophy. Fifty-three healthy children after routine laboratory, imaging and clinical examinations, with adenoid and/or tonsillar hypertrophy were evaluated before and 3 months after adenotonsillectomy for cardiac functions using M mode and Doppler echocardiography. The mean age of cases was 6.4±3.0 years, 34 (65%) were male, and 19 (35%) were female. Pulmonary hypertension was observed to be mild in 3 patients and moderate in 1 patient preoperatively. When the preoperative and postoperative echocardiographic measurements of the patients were compared, the tricuspid valve E wave velocity, the E/A ratio (E, early diastolic flow rate; A, late diastolic flow rate), and the TAPSE values were determined to be significantly higher postoperatively (P<0.05). The tricuspid valve deceleration time, the isovolumetric relaxation time and the systolic pulmonary artery pressure were found to be significantly lower compared to the preoperative values (P<0.05). Adenoidectomy and/or tonsillectomy may prevent cardiac dysfunctions that can develop in the later periods due to adenoid and/or tonsil hypertrophy in children, before the appearance of the clinical findings of cardiac failure.

Influence of antipsychotic agents on heart rate variability in male WKY rats: implications for cardiovascular safety.

PubMed

Wang, Ying-Chieh; Chen, Chun-Yu; Kuo, Terry B J; Lai, Ching-Jung; Yang, Cheryl C H

2012-06-01

Sudden cardiac death is higher among schizophrenic patients and is associated with parasympathetic hypoactivity. Antipsychotic agents are highly suspected to be a precipitating factor. Thus, we aimed to test if the antipsychotics haloperidol, risperidone and clozapine affect cardiac autonomic function, excluding the confounding effect of altered sleep structure by the drugs. In this study, haloperidol, risperidone and clozapine were given separately by intraperitoneal injection to male Wistar-Kyoto rats for 5 days. Electroencephalogram (EEG), electromyogram (EMG) and electrocardiographic signals were recorded at baseline and 5 days after drug treatments. Sleep scoring was based on EEG and EMG signals. Cardiac autonomic function was assessed using heart rate variability analysis. Clozapine increased heart rate and suppressed cardiac sympathetic and parasympathetic activity. Cardiac acceleration was more severe during sleep. Haloperidol tended to decrease heart rate while risperidone mildly increased heart rate; however, their effects were less obvious than those of clozapine. There was a significant drug-by-stage interaction on several heart rate variability measures. Taking this evidence as a whole, we conclude that haloperidol has a better level of cardiovascular safety than either risperidone or clozapine. Application of this approach to other psychotropic agents in the future will be a useful and helpful way to evaluate the cardiovascular safety of the various psychotropic medications that are in clinical use. Copyright © 2012 S. Karger AG, Basel.

Cardiac parasympathetic regulation in obese women with binge eating disorder.

PubMed

Friederich, H-C; Schild, S; Schellberg, D; Quenter, A; Bode, C; Herzog, W; Zipfel, S

2006-03-01

Obese individuals with a binge eating disorder (BED) differ from obese non-binge eaters (NBED) with respect to (a) eating behaviour, (b) psychiatric comorbidity and (c) level of psychosocial distress. The aim of the study was to explore whether these three factors have an influence on cardiac parasympathetic function, that is independent of obesity: as alterations in cardiac parasympathetic function may have a role in the higher cardiovascular mortality that is present in obese individuals. In total, 38 obese women (BMI>30 kg/m(2)), with a BED and 34 age and BMI matched healthy controls (NBED) completed a laboratory stress protocol that incorporated a baseline resting period, Head-up Tilt Testing (HUT) and two challenging mental tasks. Heart rate and blood pressure were measured continuously during the protocol. Parasympathetic cardiac regulation was assessed as the high frequency component of heart rate variability (HRV-HF). Mental challenge led to an augmented reduction of HRV-HF in obese binge eaters, which was linked to the binge eating frequency and hunger perception, but not to psychiatric comorbidity. During baseline conditions and HUT, no significant differences in parasympathetic measures were observed between the two subject groups. Subjects with a BED showed greater reduction in parasympathetic cardiac control (HRV-HF) during mental stress, suggesting higher stress vulnerability in women with a BED. Longitudinal investigations are necessary to evaluate whether this is associated with an increased cardiovascular mortality.

Biomaterial strategies for alleviation of myocardial infarction

PubMed Central

Venugopal, Jayarama Reddy; Prabhakaran, Molamma P.; Mukherjee, Shayanti; Ravichandran, Rajeswari; Dan, Kai; Ramakrishna, Seeram

2012-01-01

World Health Organization estimated that heart failure initiated by coronary artery disease and myocardial infarction (MI) leads to 29 per cent of deaths worldwide. Heart failure is one of the leading causes of death in industrialized countries and is expected to become a global epidemic within the twenty-first century. MI, the main cause of heart failure, leads to a loss of cardiac tissue impairment of left ventricular function. The damaged left ventricle undergoes progressive ‘remodelling’ and chamber dilation, with myocyte slippage and fibroblast proliferation. Repair of diseased myocardium with in vitro-engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for heart failure patients. These events reflect an apparent lack of effective intrinsic mechanism for myocardial repair and regeneration. Motivated by the desire to develop minimally invasive procedures, the last 10 years observed growing efforts to develop injectable biomaterials with and without cells to treat cardiac failure. Biomaterials evaluated include alginate, fibrin, collagen, chitosan, self-assembling peptides, biopolymers and a range of synthetic hydrogels. The ultimate goal in therapeutic cardiac tissue engineering is to generate biocompatible, non-immunogenic heart muscle with morphological and functional properties similar to natural myocardium to repair MI. This review summarizes the properties of biomaterial substrates having sufficient mechanical stability, which stimulates the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering. PMID:21900319

Effect of granulocyte colony stimulating EPC on cardiac function and myocardial energy expenditure in patients with heart failure after myocardial infarction.

PubMed

Zhao, Zilin; Luo, Jianchun; Ma, Lixian; Luo, Xia; Huang, Liangyan

2015-01-01

To study the changes of cardiac function and myocardial energy expenditure following treatment with granulocyte colony stimulating factor (G-CSF) in patients with heart failure after myocardial infarction. Thirty-eight patients with heart failure after myocardial infarction were randomized into G-CSF treatment group and control group. All the patients received conventional treatment (medication and interventional therapy), and the patients in treatment group were given additional G-CSF (600 μg/day) for 7 consecutive days. The plasma level of brain-type natriuretic peptide (BNP) and the number of endothelial progenitor cells (EPC) in the peripheral blood were detected before and at 7 days and 4 months after the treatment. The cardiac functions (LVEF, FS, LVIDs, PWTs, EDV, SV, ET) was evaluated by ultrasonic imaging before and at 2 weeks and 4 months after the treatment. The MEE and circumferential end-systolic wall stress (cESS) were calculated by correlation formula. The number of EPC was significantly higher in the treatment group than in the control group after the treatment especially at 7 days (P<0.01). In both groups, BNP level was lowered significantly after the treatment to recover the normal level (P<0.01). The cardiac functions and myocardial energy expenditure were improved in all the patients at 2 weeks and 4 months after the treatment, and the improvement was more obvious in the treatment group (P<0.05), especially in terms of the MEE and cESS was significantly lowered in the treatment group than in the control group after the treatment at 2 weeks (P<0.01), the LVEF and FS was significantly increased in the treatment group than in the control group after the treatment at 4 months (P<0.01). EPC mobilization by G-CSF can effectively improve the cardiac functions, lessen ventricular remodeling and reduce myocardial energy expenditure in patients with heart failure after myocardial infarction.

The adenosine A2A receptor — Myocardial protectant and coronary target in endotoxemia

PubMed Central

Reichelt, Melissa E.; Ashton, Kevin J.; Tan, Xing Lin; Mustafa, S. Jamal; Ledent, Catherine; Delbridge, Lea M.D.; Hofmann, Polly A.; Headrick, John P.; Morrison, R. Ray

2013-01-01

Background Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation. Methods We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO). Results Cardiac injury was evident in LPS-treated WTs, with ∼7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by 3-fold without additional demise of contraction function. Importantly, A2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A2AARs. Effects of A2AAR KO were independent of major shifts in circulating C-reactive protein (CRP) and haptoglobin. Cytokine responses were largely insensitive to A2AAR deletion; substantial LPS-induced elevations (up to 100-fold) in IFN-γ and IL-10 were unaltered in A2AAR KO mice, as were levels of IL-4 and TNF-α. However, late elevations in IL-2 and IL-5 were differentially modulated by A2AAR KO (IL-2 reduced, IL-5 increased). Data demonstrate that in the context of LPS-triggered cardiac and coronary injury, A2AAR activity protects myocardial viability without modifying contractile dysfunction, and selectively modulates cytokine (IL-2, IL-5) release. A2AARs also appear to be targeted by LPS in the coronary vasculature. Conclusions These experimental data suggest that preservation of A2AAR functionality might provide therapeutic benefit in human sepsis. PMID:22192288

Mitochondrial proteome disruption in the diabetic heart through targeted epigenetic regulation at the mitochondrial heat shock protein 70 (mtHsp70) nuclear locus.

PubMed

Shepherd, Danielle L; Hathaway, Quincy A; Nichols, Cody E; Durr, Andrya J; Pinti, Mark V; Hughes, Kristen M; Kunovac, Amina; Stine, Seth M; Hollander, John M

2018-06-01

>99% of the mitochondrial proteome is nuclear-encoded. The mitochondrion relies on a coordinated multi-complex process for nuclear genome-encoded mitochondrial protein import. Mitochondrial heat shock protein 70 (mtHsp70) is a key component of this process and a central constituent of the protein import motor. Type 2 diabetes mellitus (T2DM) disrupts mitochondrial proteomic signature which is associated with decreased protein import efficiency. The goal of this study was to manipulate the mitochondrial protein import process through targeted restoration of mtHsp70, in an effort to restore proteomic signature and mitochondrial function in the T2DM heart. A novel line of cardiac-specific mtHsp70 transgenic mice on the db/db background were generated and cardiac mitochondrial subpopulations were isolated with proteomic evaluation and mitochondrial function assessed. MicroRNA and epigenetic regulation of the mtHsp70 gene during T2DM were also evaluated. MtHsp70 overexpression restored cardiac function and nuclear-encoded mitochondrial protein import, contributing to a beneficial impact on proteome signature and enhanced mitochondrial function during T2DM. Further, transcriptional repression at the mtHsp70 genomic locus through increased localization of H3K27me3 during T2DM insult was observed. Our results suggest that restoration of a key protein import constituent, mtHsp70, provides therapeutic benefit through attenuation of mitochondrial and contractile dysfunction in T2DM. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Cardiac microRNA-133 is down-regulated in thyroid hormone-mediated cardiac hypertrophy partially via Type 1 Angiotensin II receptor.

PubMed

Diniz, Gabriela Placoná; Lino, Caroline Antunes; Guedes, Elaine Castilho; Moreira, Luana do Nascimento; Barreto-Chaves, Maria Luiza Morais

2015-09-01

Elevated thyroid hormone (TH) levels induce cardiac hypertrophy partially via type 1 Angiotensin II receptor (AT1R). MicroRNAs (miRNAs) are key regulators of cardiac homeostasis, and miR-133 has been shown to be involved in cardiac hypertrophy. However, the potential role of miR-133 in cardiac growth induced by TH is unknown. Thus, we aimed to investigate the miR-133 expression, as well as its potential role in cardiac hypertrophy in response to TH. Wistar rats were subjected to hyperthyroidism combined or not with the AT1R blocker. T3 serum levels were assessed to confirm the hyperthyroid status. TH induced cardiac hypertrophy, as evidenced by higher cardiac weight/tibia length ratio and α-actin mRNA levels, which was prevented by AT1R blocker. miR-133 expression was decreased in TH-induced cardiac hypertrophy in part through the AT1R. Additionally, the cardiac mRNA levels of miR-133 targets, SERCA2a and calcineurin were increased in hyperthyroidism partially via AT1R, as evaluated by real-time RT-PCR. Interestingly, miR-133 levels were unchanged in T3-induced cardiomyocyte hypertrophy in vitro. However, a gain-of-function study revealed that miR-133 mimic blunted the T3-induced cardiomyocyte hypertrophy in vitro. Together, our data indicate that miR-133 expression is reduced in TH-induced cardiac hypertrophy partially by the AT1R and that miR-133 mimic prevents the cardiomyocyte hypertrophy in response to T3 in vitro. These findings provide new insights regarding the mechanisms involved in the cardiac growth mediated by TH, suggesting that miR-133 plays a key role in TH-induced cardiomyocyte hypertrophy.

The Visible Heart® project and free-access website 'Atlas of Human Cardiac Anatomy'.

PubMed

Iaizzo, Paul A

2016-12-01

Pre- and post-evaluations of implantable cardiac devices require innovative and critical testing in all phases of the design process. The Visible Heart ® Project was successfully launched in 1997 and 3 years later the Atlas of Human Cardiac Anatomy website was online. The Visible Heart ® methodologies and Atlas website can be used to better understand human cardiac anatomy, disease states and/or to improve cardiac device design throughout the development process. To date, Visible ® Heart methodologies have been used to reanimate 75 human hearts, all considered non-viable for transplantation. The Atlas is a unique free-access website featuring novel images of functional and fixed human cardiac anatomies from >400 human heart specimens. Furthermore, this website includes education tutorials on anatomy, physiology, congenital heart disease and various imaging modalities. For instance, the Device Tutorial provides examples of commonly deployed devices that were present at the time of in vitro reanimation or were subsequently delivered, including: leads, catheters, valves, annuloplasty rings, leadless pacemakers and stents. Another section of the website displays 3D models of vasculature, blood volumes, and/or tissue volumes reconstructed from computed tomography (CT) and magnetic resonance images (MRI) of various heart specimens. A new section allows the user to interact with various heart models. Visible Heart ® methodologies have enabled our laboratory to reanimate 75 human hearts and visualize functional cardiac anatomies and device/tissue interfaces. The website freely shares all images, video clips and CT/MRI DICOM files in honour of the generous gifts received from donors and their families. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

The impact of cardiac arrest on the long-term wellbeing and caregiver burden of family caregivers: a prospective cohort study.

PubMed

van Wijnen, Helena Gfm; Rasquin, Sascha Mc; van Heugten, Caroline M; Verbunt, Jeanine A; Moulaert, Véronique Rm

2017-09-01

The purpose was to gain insight in the functioning of caregivers of cardiac arrest survivors at 12 months after a cardiac arrest. Secondly, the course of the wellbeing of the caregivers during the first year was studied. Finally, factors that are associated with a higher care burden at 12 months after the cardiac arrest were investigated. A total of 195 family caregivers of cardiac arrest survivors were included. Quality of life (SF-36, EuroQol-VAS), caregiver strain (CSI) and emotional functioning (HADS, IES) were measured at two weeks, three months and one year after the cardiac arrest. Thereby, the caregiver was asked to fill out the cognitive failure questionnaire (CFQ) to evaluate their view on the cognitive status of the patient. Caregiver strain was high in 16 (15%) of the caregivers at 12 months. Anxiety was present in 33 (25%) caregivers and depression in 18 (14%) caregivers at 12 months. The repeated measures MANOVA showed that during the first year the following variables improved significantly: SF-36 domains social and mental health, role physical, role emotional and vitality, caregiver strain, HADS and IES ( P<0.001). At 12 months caregiver strain correlated significantly (explained variance 63%, P=0.03) with caregiver HADS ( P=0.01), EuroQol-VAS ( P=0.02), and the CFQ ( P<0.001), all measured at 12 months after the cardiac arrest. Overall wellbeing of the caregivers improves during the first year up to normal levels, but caregivers with emotional problems or perceived cognitive problems at 12 months are at risk for developing a higher care burden.

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration.

PubMed

Formiga, Fabio R; Pelacho, Beatriz; Garbayo, Elisa; Imbuluzqueta, Izaskun; Díaz-Herráez, Paula; Abizanda, Gloria; Gavira, Juan J; Simón-Yarza, Teresa; Albiasu, Edurne; Tamayo, Esther; Prósper, Felipe; Blanco-Prieto, Maria J

2014-01-10

Acidic fibroblast growth factor (FGF1) and neuregulin-1 (NRG1) are growth factors involved in cardiac development and regeneration. Microparticles (MPs) mediate cytokine sustained release, and can be utilized to overcome issues related to the limited therapeutic protein stability during systemic administration. We sought to examine whether the administration of microparticles (MPs) containing FGF1 and NRG1 could promote cardiac regeneration in a myocardial infarction (MI) rat model. We investigated the possible underlying mechanisms contributing to the beneficial effects of this therapy, especially those linked to endogenous regeneration. FGF1- and NRG1-loaded MPs were prepared using a multiple emulsion solvent evaporation technique. Seventy-three female Sprague-Dawley rats underwent permanent left anterior descending coronary artery occlusion, and MPs were intramyocardially injected in the peri-infarcted zone four days later. Cardiac function, heart tissue remodeling, revascularization, apoptosis, cardiomyocyte proliferation, and stem cell homing were evaluated one week and three months after treatment. MPs were shown to efficiently encapsulate FGF1 and NRG1, releasing the bioactive proteins in a sustained manner. Three months after treatment, a statistically significant improvement in cardiac function was detected in rats treated with growth factor-loaded MPs (FGF1, NRG1, or FGF1/NRG1). The therapy led to inhibition of cardiac remodeling with smaller infarct size, a lower fibrosis degree and induction of tissue revascularization. Cardiomyocyte proliferation and progenitor cell recruitment were detected. Our data support the therapeutic benefit of NRG1 and FGF1 when combined with protein delivery systems for cardiac regeneration. This approach could be scaled up for use in pre-clinical and clinical studies. © 2013.

Use of diagnostic information submitted to the United Kingdom Central Cardiac Audit Database: development of categorisation and allocation algorithms.

PubMed

Brown, Kate L; Crowe, Sonya; Pagel, Christina; Bull, Catherine; Muthialu, Nagarajan; Gibbs, John; Cunningham, David; Utley, Martin; Tsang, Victor T; Franklin, Rodney

2013-08-01

To categorise records according to primary cardiac diagnosis in the United Kingdom Central Cardiac Audit Database in order to add this information to a risk adjustment model for paediatric cardiac surgery. Codes from the International Paediatric Congenital Cardiac Code were mapped to recognisable primary cardiac diagnosis groupings, allocated using a hierarchy and less refined diagnosis groups, based on the number of functional ventricles and presence of aortic obstruction. A National Clinical Audit Database. Patients Children undergoing cardiac interventions: the proportions for each diagnosis scheme are presented for 13,551 first patient surgical episodes since 2004. In Scheme 1, the most prevalent diagnoses nationally were ventricular septal defect (13%), patent ductus arteriosus (10.4%), and tetralogy of Fallot (9.5%). In Scheme 2, the prevalence of a biventricular heart without aortic obstruction was 64.2% and with aortic obstruction was 14.1%; the prevalence of a functionally univentricular heart without aortic obstruction was 4.3% and with aortic obstruction was 4.7%; the prevalence of unknown (ambiguous) number of ventricles was 8.4%; and the prevalence of acquired heart disease only was 2.2%. Diagnostic groups added to procedural information: of the 17% of all operations classed as "not a specific procedure", 97.1% had a diagnosis identified in Scheme 1 and 97.2% in Scheme 2. Diagnostic information adds to surgical procedural data when the complexity of case mix is analysed in a national database. These diagnostic categorisation schemes may be used for future investigation of the frequency of conditions and evaluation of long-term outcome over a series of procedures.

Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

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

Lin, Xinchun

Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, andmore » improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.« less

Feasibility of dynamic cardiac ultrasound transmission via mobile phone for basic emergency teleconsultation.

PubMed

Lim, Tae Ho; Choi, Hyuk Joong; Kang, Bo Seung

2010-01-01

We assessed the feasibility of using a camcorder mobile phone for teleconsulting about cardiac echocardiography. The diagnostic performance of evaluating left ventricle (LV) systolic function was measured by three emergency medicine physicians. A total of 138 short echocardiography video sequences (from 70 subjects) was selected from previous emergency room ultrasound examinations. The measurement of LV ejection fraction based on the transmitted video displayed on a mobile phone was compared with the original video displayed on the LCD monitor of the ultrasound machine. The image quality was evaluated using the double stimulation impairment scale (DSIS). All observers showed high sensitivity. There was an improvement in specificity with the observer's increasing experience of cardiac ultrasound. Although the image quality of video on the mobile phone was lower than that of the original, a receiver operating characteristic (ROC) analysis indicated that there was no significant difference in diagnostic performance. Immediate basic teleconsulting of echocardiography movies is possible using current commercially-available mobile phone systems.

Characterizing cardiac dysfunction in fetuses with left congenital diaphragmatic hernia.

PubMed

Cruz-Lemini, Mónica; Valenzuela-Alcaraz, Brenda; Granados-Montiel, Julio; Martínez, Josep M; Crispi, Fátima; Gratacós, Eduard; Cruz-Martínez, Rogelio

2018-03-23

To evaluate cardiac function by conventional echocardiography and tissue Doppler imaging in fetuses with left congenital diaphragmatic hernia (CDH). Conventional echocardiography (myocardial performance index, ventricular filling velocities, and E/A ratios) and tissue Doppler imaging (annular myocardial peak velocities, E/E' and E'/A' ratios) in mitral, septal, and tricuspid annulus were evaluated in a cohort of 31 left-sided CDH fetuses and compared with 75 controls matched for gestational age 2:1. In comparison to controls, CDH fetuses had prolonged isovolumetric time periods (isovolumetric contraction time 35 ms vs 28 ms, P < .001), with higher myocardial performance index (0.49 vs 0.42, P < .001) and tricuspid E/A ratios (0.77 vs 0.72, P = .033). Longitudinal function assessed by tissue Doppler showed signs of impaired relaxation (mitral lateral A' 8.0 vs 10.1 cm/s, P < .001 and an increased mitral lateral E'/A' ratio 0.93 vs 0.78, P < .001) in the CDH fetuses as compared with controls, with preserved systolic function. Left CDH fetuses show echocardiographic signs of diastolic dysfunction, probably secondary to fetal heart compression, maintaining a preserved systolic function. © 2018 John Wiley & Sons, Ltd.

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

Postnatal Ablation of Foxm1 from Cardiomyocytes Causes Late Onset Cardiac Hypertrophy and Fibrosis without Exacerbating Pressure Overload-Induced Cardiac Remodeling

PubMed Central

Bolte, Craig; Zhang, Yufang; York, Allen; Kalin, Tanya V.; Schultz, Jo El J.; Molkentin, Jeffery D.; Kalinichenko, Vladimir V.

2012-01-01

Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2) plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1fl/fl mice were generated. Surprisingly, αMHC-Cre/Foxm1fl/fl mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis. PMID:23144938

Incidence and implication of vocal fold paresis following neonatal cardiac surgery.

PubMed

Dewan, Karuna; Cephus, Constance; Owczarzak, Vicki; Ocampo, Elena

2012-12-01

To study the incidence and implications of vocal fold paresis (VFP) following congenital neonatal cardiac surgery. Retrospective chart review. All neonates who underwent median sternotomy for cardiac surgery from May 2007 to May 2008 were evaluated. Flexible laryngoscopy was performed to evaluate vocal fold function after extubation. Swallow evaluation and a modified barium swallow study were performed prior to initiating oral feeding if the initial screening was abnormal. A total of 101 neonates underwent cardiac surgery during the study period. Ninety-four patients underwent a median sternotomy, and 76 of these were included in the study. Fifteen (19.7%) had vocal fold paresis (VFP) postoperatively. Almost 27% of the patients with aortic arch surgery had VFP while only 4.1% of the patients with nonaortic arch surgery developed VFP (P=0.02) Those patients who underwent aortic arch surgery weighed significantly less (P<0.01). All the patients with VFP had significant morbidity related to swallowing and nutrition (P=0.01) and required longer postsurgical hospitalization (P=0.02). The reported incidence of VFP following cardiac surgery via median sternotomy ranges between 1.7% and 67% depending on the type of surgery and the weight of the infant at the time of surgery. In our cohort, 19.7% had VFP. Surgery requiring aortic arch manipulation had a higher incidence of complications and required longer hospitalizations. These results may be used to improve informed consent and to manage postoperative expectations by identifying patients who are at higher risk for complications. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

A comparative analysis of alternative approaches for quantifying nonlinear dynamics in cardiovascular system.

PubMed

Chen, Yun; Yang, Hui

2013-01-01

Heart rate variability (HRV) analysis has emerged as an important research topic to evaluate autonomic cardiac function. However, traditional time and frequency-domain analysis characterizes and quantify only linear and stationary phenomena. In the present investigation, we made a comparative analysis of three alternative approaches (i.e., wavelet multifractal analysis, Lyapunov exponents and multiscale entropy analysis) for quantifying nonlinear dynamics in heart rate time series. Note that these extracted nonlinear features provide information about nonlinear scaling behaviors and the complexity of cardiac systems. To evaluate the performance, we used 24-hour HRV recordings from 54 healthy subjects and 29 heart failure patients, available in PhysioNet. Three nonlinear methods are evaluated not only individually but also in combination using three classification algorithms, i.e., linear discriminate analysis, quadratic discriminate analysis and k-nearest neighbors. Experimental results show that three nonlinear methods capture nonlinear dynamics from different perspectives and the combined feature set achieves the best performance, i.e., sensitivity 97.7% and specificity 91.5%. Collectively, nonlinear HRV features are shown to have the promise to identify the disorders in autonomic cardiovascular function.

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

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.

Preexisting depressive symptoms are associated with long-term cognitive decline in patients after cardiac surgery.

PubMed

Patron, Elisabetta; Messerotti Benvenuti, Simone; Zanatta, Paolo; Polesel, Elvio; Palomba, Daniela

2013-01-01

To examine whether preoperative psychological dysfunctions rather than intraoperative factors may differentially predict short- and long-term postoperative cognitive decline (POCD) in patients after cardiac surgery. Forty-two patients completed a psychological evaluation, including the Trail Making Test Part A and B (TMT-A/B), the memory with 10/30-s interference, the phonemic verbal fluency and the Center for Epidemiological Studies of Depression (CES-D) scale for cognitive functions and depressive symptoms, respectively, before surgery, at discharge and at 18-month follow-up. Ten (24%) and 11 (26%) patients showed POCD at discharge and at 18-month follow-up, respectively. The duration of cardiopulmonary bypass significantly predicted short-term POCD [odds ratio (OR)=1.04, P<.05], whereas preoperative psychological factors were unrelated to cognitive decline at discharge. Conversely, long-term cognitive decline after cardiac surgery was significantly predicted by preoperative scores in the CES-D (OR=1.26, P<.03) but not by intraoperative variables (all Ps >.23). Our findings showed that preexisting depressive symptoms rather than perioperative risk factors are associated with cognitive decline 18 months after cardiac surgery. This study suggests that a preoperative psychological evaluation of depressive symptoms is essential to anticipate which patients are likely to show long-term cognitive decline after cardiac surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of hepatocyte growth factor in myocarditis rats induced by immunization with porcine cardiac myosin

PubMed Central

Nakano, Jota; Marui, Akira; Muranaka, Hiroyuki; Masumoto, Hidetoshi; Noma, Hisashi; Tabata, Yasuhiko; Ido, Akio; Tsubouchi, Hirohito; Ikeda, Tadashi; Sakata, Ryuzo

2014-01-01

OBJECTIVES Myocarditis is considered one of the major causes of dilated cardiomyopathy. Hepatocyte growth factor (HGF) has pleiotropic activities that promote tissue regeneration and facilitate functional improvement of injured tissue. We investigated whether the epicardial sustained-release of HGF, using gelatin hydrogel sheets, improves cardiac function in a chronic myocarditis rat model. METHODS Six weeks after Lewis rats were immunized with porcine cardiac myosin to establish autoimmune myocarditis, HGF- or normal saline (NS)-incorporated gelatin hydrogel sheets were applied to the epicardium (G-HGF and G-NS, respectively). At either 2 or 4 weeks after treatment, these were compared with the Control myocarditis group. Cardiac function was evaluated by echocardiography and cardiac catheterization. Development of fibrosis was determined by histological study and expression of transforming growth factor-β1 (TGF-β1). Bax and Bcl-2 levels were measured to evaluate apoptotic activity. RESULTS At both points, fractional shortening and end-systolic elastance were higher in the G-HGF group than in the Control and G-NS groups (P < 0.01). Fractional shortening at 2 weeks of each group were as follows: 31.0 ± 0.9%, 24.8 ± 2.7% and 48.6 ± 2.6% (Control, G-NS and G-HGF, respectively). The ratio of the fibrotic area of the myocardium was lower in the G-HGF group than in the Control and G-NS groups at 2 weeks (G-HGF, 8.8 ± 0.9%; Control, 17.5 ± 0.2%; G-NS, 15.6 ± 0.7%; P < 0.01). The ratio at 4 weeks was lower in the G-HGF group than in the G-NS group (10.9 ± 1.4% vs 18.5 ± 1.3%; P < 0.01). The mRNA expression of TGF-β1 in the G-HGF group was lower than in the Control group at 2 weeks (0.6 ± 0.1 vs 1.1 ± 0.2) and lower than that in the G-NS group at 4 weeks (0.7 ± 0.1 vs 1.3 ± 0.2). The Bax-to-Bcl-2 ratios at both points were lower in the G-HGF group than in the Control group. CONCLUSIONS Sustained-released HGF markedly improves cardiac function in chronic myocarditis rats. The antifibrotic and antiapoptotic actions of HGF may contribute to the improvement. HGF-incorporated gelatin hydrogel sheet can be a new therapeutic modality for myocarditis. PMID:24327573

Amelioration of High Fructose-Induced Cardiac Hypertrophy by Naringin.

PubMed

Park, Jung Hyun; Ku, Hyeong Jun; Kim, Jae Kyeom; Park, Jeen-Woo; Lee, Jin Hyup

2018-06-21

Heart failure is a frequent unfavorable outcome of pathological cardiac hypertrophy. Recent increase in dietary fructose consumption mirrors the rise in prevalence of cardiovascular diseases such as cardiac hypertrophy leading to concerns raised by public health experts. Mitochondria, comprising 30% of cardiomyocyte volume, play a central role in modulating redox-dependent cellular processes such as metabolism and apoptosis. Furthermore, mitochondrial dysfunction is a key cause of pathogenesis of fructose-induced cardiac hypertrophy. Naringin, a major flavanone glycoside in citrus species, has displayed strong antioxidant potential in models of oxidative stress. In this study, we evaluated protective effects of naringin against fructose-induced cardiac hypertrophy and associated mechanisms of action, using in vitro and in vivo models. We found that naringin suppressed mitochondrial ROS production and mitochondrial dysfunction in cardiomyocytes exposed to fructose and consequently reduced cardiomyocyte hypertrophy by regulating AMPK-mTOR signaling axis. Furthermore, naringin counteracted fructose-induced cardiomyocyte apoptosis, and this function of naringin was linked to its ability to inhibit ROS-dependent ATM-mediated p53 signaling. This result was supported by observations in in vivo mouse model of cardiac hypertrophy. These findings indicate a novel role for naringin in protecting against fructose-induced cardiac hypertrophy and suggest unique therapeutic strategies for prevention of cardiovascular diseases.

Frailty and cardiac rehabilitation: A call to action from the EAPC Cardiac Rehabilitation Section.

PubMed

Vigorito, Carlo; Abreu, Ana; Ambrosetti, Marco; Belardinelli, Romualdo; Corrà, Ugo; Cupples, Margaret; Davos, Constantinos H; Hoefer, Stefan; Iliou, Marie-Christine; Schmid, Jean-Paul; Voeller, Heinz; Doherty, Patrick

2017-04-01

Frailty is a geriatric syndrome characterised by a vulnerability status associated with declining function of multiple physiological systems and loss of physiological reserves. Two main models of frailty have been advanced: the phenotypic model (primary frailty) or deficits accumulation model (secondary frailty), and different instruments have been proposed and validated to measure frailty. However measured, frailty correlates to medical outcomes in the elderly, and has been shown to have prognostic value for patients in different clinical settings, such as in patients with coronary artery disease, after cardiac surgery or transvalvular aortic valve replacement, in patients with chronic heart failure or after left ventricular assist device implantation. The prevalence, clinical and prognostic relevance of frailty in a cardiac rehabilitation setting has not yet been well characterised, despite the increasing frequency of elderly patients in cardiac rehabilitation, where frailty is likely to influence the onset, type and intensity of the exercise training programme and the design of tailored rehabilitative interventions for these patients. Therefore, we need to start looking for frailty in elderly patients entering cardiac rehabilitation programmes and become more familiar with some of the tools to recognise and evaluate the severity of this condition. Furthermore, we need to better understand whether exercise-based cardiac rehabilitation may change the course and the prognosis of frailty in cardiovascular patients.

Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis.

PubMed

Huang, Zhan-Peng; Kataoka, Masaharu; Chen, Jinghai; Wu, Gengze; Ding, Jian; Nie, Mao; Lin, Zhiqiang; Liu, Jianming; Hu, Xiaoyun; Ma, Lixin; Zhou, Bin; Wakimoto, Hiroko; Zeng, Chunyu; Kyselovic, Jan; Deng, Zhong-Liang; Seidman, Christine E; Seidman, J G; Pu, William T; Wang, Da-Zhi

2015-11-02

Cardiomyopathy is a common human disorder that is characterized by contractile dysfunction and cardiac remodeling. Genetic mutations and altered expression of genes encoding many signaling molecules and contractile proteins are associated with cardiomyopathy; however, how cardiomyocytes sense pathophysiological stresses in order to then modulate cardiac remodeling remains poorly understood. Here, we have described a regulator in the heart that harmonizes the progression of cardiac hypertrophy and dilation. We determined that expression of the myocyte-enriched protein cardiac ISL1-interacting protein (CIP, also known as MLIP) is reduced in patients with dilated cardiomyopathy. As CIP is highly conserved between human and mouse, we evaluated the effects of CIP deficiency on cardiac remodeling in mice. Deletion of the CIP-encoding gene accelerated progress from hypertrophy to heart failure in several cardiomyopathy models. Conversely, transgenic and AAV-mediated CIP overexpression prevented pathologic remodeling and preserved cardiac function. CIP deficiency combined with lamin A/C deletion resulted in severe dilated cardiomyopathy and cardiac dysfunction in the absence of stress. Transcriptome analyses of CIP-deficient hearts revealed that the p53- and FOXO1-mediated gene networks related to homeostasis are disturbed upon pressure overload stress. Moreover, FOXO1 overexpression suppressed stress-induced cardiomyocyte hypertrophy in CIP-deficient cardiomyocytes. Our studies identify CIP as a key regulator of cardiomyopathy that has potential as a therapeutic target to attenuate heart failure progression.

Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis

PubMed Central

Huang, Zhan-Peng; Kataoka, Masaharu; Chen, Jinghai; Wu, Gengze; Ding, Jian; Nie, Mao; Lin, Zhiqiang; Liu, Jianming; Hu, Xiaoyun; Ma, Lixin; Zhou, Bin; Wakimoto, Hiroko; Zeng, Chunyu; Kyselovic, Jan; Deng, Zhong-Liang; Seidman, Christine E.; Seidman, J.G.; Pu, William T.; Wang, Da-Zhi

2015-01-01

Cardiomyopathy is a common human disorder that is characterized by contractile dysfunction and cardiac remodeling. Genetic mutations and altered expression of genes encoding many signaling molecules and contractile proteins are associated with cardiomyopathy; however, how cardiomyocytes sense pathophysiological stresses in order to then modulate cardiac remodeling remains poorly understood. Here, we have described a regulator in the heart that harmonizes the progression of cardiac hypertrophy and dilation. We determined that expression of the myocyte-enriched protein cardiac ISL1-interacting protein (CIP, also known as MLIP) is reduced in patients with dilated cardiomyopathy. As CIP is highly conserved between human and mouse, we evaluated the effects of CIP deficiency on cardiac remodeling in mice. Deletion of the CIP-encoding gene accelerated progress from hypertrophy to heart failure in several cardiomyopathy models. Conversely, transgenic and AAV-mediated CIP overexpression prevented pathologic remodeling and preserved cardiac function. CIP deficiency combined with lamin A/C deletion resulted in severe dilated cardiomyopathy and cardiac dysfunction in the absence of stress. Transcriptome analyses of CIP-deficient hearts revealed that the p53- and FOXO1-mediated gene networks related to homeostasis are disturbed upon pressure overload stress. Moreover, FOXO1 overexpression suppressed stress-induced cardiomyocyte hypertrophy in CIP-deficient cardiomyocytes. Our studies identify CIP as a key regulator of cardiomyopathy that has potential as a therapeutic target to attenuate heart failure progression. PMID:26436652

Never in mitosis gene A related kinase-6 attenuates pressure overload-induced activation of the protein kinase B pathway and cardiac hypertrophy.

PubMed

Bian, Zhouyan; Liao, Haihan; Zhang, Yan; Wu, Qingqing; Zhou, Heng; Yang, Zheng; Fu, Jinrong; Wang, Teng; Yan, Ling; Shen, Difei; Li, Hongliang; Tang, Qizhu

2014-01-01

Cardiac hypertrophy appears to be a specialized form of cellular growth that involves the proliferation control and cell cycle regulation. NIMA (never in mitosis, gene A)-related kinase-6 (Nek6) is a cell cycle regulatory gene that could induce centriole duplication, and control cell proliferation and survival. However, the exact effect of Nek6 on cardiac hypertrophy has not yet been reported. In the present study, the loss- and gain-of-function experiments were performed in Nek6 gene-deficient (Nek6-/-) mice and Nek6 overexpressing H9c2 cells to clarify whether Nek6 which promotes the cell cycle also mediates cardiac hypertrophy. Cardiac hypertrophy was induced by transthoracic aorta constriction (TAC) and then evaluated by echocardiography, pathological and molecular analyses in vivo. We got novel findings that the absence of Nek6 promoted cardiac hypertrophy, fibrosis and cardiac dysfunction, which were accompanied by a significant activation of the protein kinase B (Akt) signaling in an experimental model of TAC. Consistent with this, the overexpression of Nek6 prevented hypertrophy in H9c2 cells induced by angiotonin II and inhibited Akt signaling in vitro. In conclusion, our results demonstrate that the cell cycle regulatory gene Nek6 is also a critical signaling molecule that helps prevent cardiac hypertrophy and inhibits the Akt signaling pathway.

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.

Aerobic exercise training promotes additional cardiac benefits better than resistance exercise training in postmenopausal rats with diabetes.

PubMed

Quinteiro, Hugo; Buzin, Morgana; Conti, Filipe Fernandes; Dias, Danielle da Silva; Figueroa, Diego; Llesuy, Susana; Irigoyen, Maria-Cláudia; Sanches, Iris Callado; De Angelis, Kátia

2015-05-01

The aim of this study was to evaluate the effects of aerobic exercise training or resistance exercise training on cardiac morphometric, functional, and oxidative stress parameters in rats with ovarian hormone deprivation and diabetes. Female Wistar rats (200-220 g) were divided into a sham-operated group (euglycemic sham-operated sedentary [ES]; n = 8) and three ovariectomized (bilateral removal of ovaries) and diabetic (streptozotocin 50 mg/kg IV) groups as follows: diabetic ovariectomized sedentary (DOS; n = 8), diabetic ovariectomized undergoing aerobic exercise training (DOTA; n = 8), and diabetic ovariectomized undergoing resistance exercise training (DOTR; n = 8). After 8 weeks of resistance (ladder) or aerobic (treadmill) exercise training, left ventricle function and morphometry were evaluated by echocardiography, whereas oxidative stress was evaluated at the left ventricle. The DOS group presented with increased left ventricle cavity in diastole and relative wall thickness (RWT), and these changes were attenuated in both DOTA and DOTR groups. Systolic and diastolic function was impaired in the DOS group compared with the ES group, and only the DOTA group was able to reverse this dysfunction. Lipoperoxidation and glutathione redox balance were improved in both trained groups compared with the DOS group. Glutathione peroxidase and superoxide dismutase were higher in the DOTA group than in the other studied groups. Correlations were observed between lipoperoxidation and left ventricle cavity in diastole (r = 0.55), between redox balance and RWT (r = 0.62), and between lipoperoxidation and RWT (r = -0.60). Aerobic exercise training and resistance exercise training promote attenuation of cardiac morphometric dysfunction associated with a reduction in oxidative stress in an experimental model of diabetes and menopause. However, only dynamic aerobic exercise training is able to attenuate systolic and diastolic dysfunction under this condition.

Analysis of Regional Left Ventricular Strain in Patients with Chagas Disease and Normal Left Ventricular Systolic Function.

PubMed

Gomes, Victor Augusto M; Alves, Gabriel F; Hadlich, Marcelo; Azevedo, Clerio F; Pereira, Iane M; Santos, Carla Renata F; Brasil, Pedro Emmanuel A A; Sangenis, Luiz Henrique C; Cunha, Ademir B; Xavier, Sergio S; Saraiva, Roberto M

2016-07-01

Chagas heart disease has a high socioeconomic burden, and any strategy to detect early myocardial damage is welcome. Speckle-tracking echocardiography assesses global and segmental left ventricular (LV) systolic function, yielding values of two-dimensional strain (ε). The aim of this study was to determine if patients with chronic Chagas disease and normal LV ejection fractions present abnormalities in global and segmental LV ε. In this prospective study, patients with Chagas disease with no evidence of cardiac involvement (group I; n = 83) or at stage A of the cardiac form (i.e., with changes limited to the electrocardiogram) (group A; n = 42) and 43 control subjects (group C) underwent evaluation of global and segmental LV ε by speckle-tracking echocardiography. A subset of randomly selected patients in group A underwent cardiac magnetic resonance imaging and repeated echocardiography 3.5 ± 0.8 years after the first evaluation. Mean age, chamber dimensions, and LV ejection fraction were similar among the groups. Global longitudinal (group C, -19 ± 2%; group I, -19 ± 2%; group A, -19 ± 2%), circumferential (group C, -19 ± 3%; group I, -20 ± 3%; group A, -19 ± 3%), and radial (group C, 46 ± 10%; group I, 45 ± 13%; group A, 42 ± 14%) LV ε were similar among the groups. Segmental longitudinal, circumferential, and radial LV ε were similar across the studied groups. Seven of 14 patients had areas of fibrosis on cardiac magnetic resonance imaging. Patients with fibrosis had lower global longitudinal (-15 ± 2% vs -18 ± 2%, P = .004), circumferential (-14 ± 2% vs -19 ± 2%, P = .002), and radial LV ε (36 ± 13% vs 54 ± 12%, P = .02) than those without cardiac fibrosis despite similar LV ejection fractions. Patients with fibrosis had lower radial LV ε in the basal inferoseptal wall than patients without cardiac fibrosis (27 ± 17% vs 60 ± 15%, P = .04). Patients with chronic Chagas disease and normal global and segmental LV systolic function on two-dimensional echocardiography had global and segmental LV ε similar to that of control subjects. However, those in the early stages of the cardiac form and cardiac fibrosis had lower global longitudinal, circumferential, and radial LV ε. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Instant images of the human heart using a new, whole-body MR imaging system.

PubMed

Rzedzian, R R; Pykett, I L

1987-08-01

An extremely rapid MR imaging technique is described, and its use on a new 2.0-T high-speed MR system is demonstrated. This implementation permits complete filling of the two-dimensional spatial-frequency domain (k-space) within an acquisition window of 26 msec. With this acquisition window placed under the spin-echo signal envelope generated by a 90-180 degree pulse pair, the image contrast is the same as that of a conventional spin-echo pulse sequence. Resultant proton images have a motion-independent voxel resolution of 0.08 cm3 and a signal-to-noise ratio for cardiac muscle of approximately 30:1 (for TE = 30 msec) with no signal averaging. The pulse sequence yields images that are chemical shift-resolved. The total proton density distribution is optionally presented with lipid and water signals displayed in two different colors. Cardiac function is observed by displaying multiple images, acquired at different times in successive cardiac periods, in a cyclic movie format. Such motion pictures are obtained within a single period of suspended respiration, thereby assuring freedom from respiratory related motion artifacts. As preliminary examples, we present MR images of the normal adult human heart that have total acquisition times of only 40 msec/image and that show the major cardiac anatomy. Frames from movie loops show contraction of cardiac chambers and left ventricular wall thickening. The extremely rapid acquisition time of this technique suggests that it may hold promise for the routine and cost-effective evaluation of cardiac anatomy and function.

Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

PubMed Central

Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

2012-01-01

Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

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.

Therapeutic effect of a novel Wnt pathway inhibitor on cardiac regeneration after myocardial infarction.

PubMed

Yang, Dezhong; Fu, Wenbin; Li, Liangpeng; Xia, Xuewei; Liao, Qiao; Yue, Rongchuan; Chen, Hongmei; Chen, Xiongwen; An, Songzhu; Zeng, Chunyu; Wang, Wei Eric

2017-12-15

After myocardial infarction (MI), the heart is difficult to repair because of great loss of cardiomyoctyes and lack of cardiac regeneration. Novel drug candidates that aim at reducing pathological remodeling and stimulating cardiac regeneration are highly desirable. In the present study, we identified if and how a novel porcupine inhibitor CGX1321 influenced MI and cardiac regeneration. Permanent ligation of left anterior descending (LAD) coronary artery was performed in mice to induce MI injury. Cardiac function was measured by echocardiography, infarct size was examined by TTC staining. Fibrosis was evaluated with Masson's trichrome staining and vimentin staining. As a result, CGX1321 administration blocked the secretion of Wnt proteins, and inhibited both canonical and non-canonical Wnt signaling pathways. CGX1321 improved cardiac function, reduced myocardial infarct size, and fibrosis of post-MI hearts. CGX1321 significantly increased newly formed cardiomyocytes in infarct border zone of post-MI hearts, evidenced by the increased EdU + cardiomyocytes. Meanwhile, CGX1321 increased Ki67 + and phosphohistone H3 (PH3 + ) cardiomyocytes in culture, indicating enhanced cardiomyocyte proliferation. The mRNA microarray showed that CGX1321 up-regulated cell cycle regulating genes such as Ccnb1 and Ccne1 CGX1321 did not alter YAP protein phosphorylation and nuclear translocation in cardiomyocytes. In conclusion, porcupine inhibitor CGX1321 reduces MI injury by limiting fibrosis and promoting regeneration. It promotes cardiomyocyte proliferation by stimulating cell cycle regulating genes with a Hippo/YAP-independent pathway. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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.

Depression and reduced heart rate variability after cardiac surgery: the mediating role of emotion regulation.

PubMed

Patron, Elisabetta; Messerotti Benvenuti, Simone; Favretto, Giuseppe; Gasparotto, Renata; Palomba, Daniela

2014-02-01

Heart rate variability (HRV), as an index of autonomic nervous system (ANS) functioning, is reduced by depression after cardiac surgery, but the underlying mechanisms of this relationship are poorly understood. Poor emotion regulation as a core symptom of depression has also been associated with altered ANS functioning. The present study aimed to examine whether emotion dysregulation could be a mediator of the depression-reduced HRV relationship observed after cardiac surgery. Self-reported emotion regulation and four-minute HRV were measured in 25 depressed and 43 nondepressed patients after cardiac surgery. Mediation analysis was conducted to evaluate emotion regulation as a mediator of the depression-reduced HRV relationship. Compared to nondepressed patients, those with depression showed lower standard deviation of normal-to-normal (NN) intervals (p<.05), root mean square successive difference of NN intervals (p<.004), and number of interval differences of successive NN intervals greater than 50ms (NN50) (p<.05). Increased low frequency (LF) in normalized units (n.u.) and reduced high frequency (HF) n.u. were also found in depressed compared to nondepressed patients (p's<.01). Mediation analysis revealed that suppression of emotion-expressive behavior partially mediated the effect of depression on LF n.u. and HF n.u. Results confirmed previous findings showing that depression is associated with reduced HRV, especially a reduced vagal tone and a sympathovagal imbalance, after cardiac surgery. This study also provides preliminary evidence that increased trait levels of suppression of emotion-expressive behavior may mediate the depression-related sympathovagal imbalance after cardiac surgery. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Reproducibility of cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance for measuring left ventricular strains, torsion, and synchrony in mice.

PubMed

Haggerty, Christopher M; Kramer, Sage P; Binkley, Cassi M; Powell, David K; Mattingly, Andrea C; Charnigo, Richard; Epstein, Frederick H; Fornwalt, Brandon K

2013-08-27

Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance (CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE CMR would show excellent inter-test and inter-observer reproducibility for advanced measures of left ventricular (LV) function in mice. Five normal mice (C57BL/6) and four mice with depressed cardiac function (diet-induced obesity) were imaged twice, two days apart, on a 7T ClinScan MR system. Images were acquired with 15-20 frames per cardiac cycle in three short-axis (basal, mid, apical) and two long-axis orientations (4-chamber and 2-chamber). LV strain, twist, torsion, and measures of synchrony were quantified. Images from both days were analyzed by one observer to quantify inter-test reproducibility, while inter-observer reproducibility was assessed by a second observer's analysis of day-1 images. The coefficient of variation (CoV) was used to quantify reproducibility. LV strains and torsion were highly reproducible on both inter-observer and inter-test bases with CoVs ≤ 15%, and inter-observer reproducibility was generally better than inter-test reproducibility. However, end-systolic twist angles showed much higher variance, likely due to the sensitivity of slice location within the sharp longitudinal gradient in twist angle. Measures of synchrony including the circumferential (CURE) and radial (RURE) uniformity of strain indices, showed excellent reproducibility with CoVs of 1% and 3%, respectively. Finally, peak measures (e.g., strains) were generally more reproducible than the corresponding rates of change (e.g., strain rate). Cine DENSE CMR is a highly reproducible technique for quantification of advanced measures of left ventricular cardiac function in mice including strains, torsion and measures of synchrony. However, myocardial twist angles are not reproducible and future studies should instead report torsion.

Long-term functional and echocardiographic assessment after penetrating cardiac injury: 5-year follow-up results.

PubMed

Carr, John Alfred; Buterakos, Roxanne; Bowling, William M; Janson, Lisa; Kralovich, Kurt A; Copeland, Craig; Link, Renee; Roiter, Cecilia; Casey, Gregory; Wagner, James W

2011-03-01

There is almost no data describing the long-term functional outcome of patients after penetrating cardiac injury. A retrospective study at a Level I trauma center from 2000 to 2009. Sixty-three patients had penetrating cardiac injuries from 28 stabbings and 35 gunshots. Men comprised 89% (56) of the patients. Overall, there were 21 survivors (33%) and 42 died in the emergency room or perioperative period. The mean age did not significantly differ between survivors (36 years ± 12 years) compared with those who died (30 years ± 11 years; p=0.07). There was an increased chance of survival after being stabbed compared with being shot (17 patients vs. 4 patients; odds ratio=12; p=0.002). Thirteen (62%) had injuries to the right ventricle only. Three patients died during follow-up: one from lung cancer and two other patients died from myocardial infarctions, one 9 years later at the age of 45 years and the other 8 years later at the age of 55 years. The survivors had functional follow-up evaluations from 2 months to 114 months (median, 71; interquartile range, 34-92 months) and echocardiographic follow-up from 2 months to 107 months (median, 64; interquartile range, 31-84 months) after their injuries. Functionally, all patients were in NYHA class 1 status, except one patient in class II who was 54 years old and had a mild exertional limitation. The previously injured area could only be identified by echocardiogram in one patient who had a patch repair of a ventricular septal defect (VSD). The mean ejection fraction improved over time from a mean of 51% ± 8% in the immediate postoperative period to 60% ± 9% after a mean follow-up of 59 months (p=0.01). After surgery, 43% of patients had a mild to moderate pericardial effusion; however, the long-term follow-up studies showed that all these had resolved. Wall motion abnormalities occurred in 33% of patients in the immediate postoperative period and, again, all these resolved during long-term follow-up. Patients who survive penetrating cardiac injuries, without coronary arterial or valvular disruption, have an excellent long-term functional outcome with minimal subsequent cardiac morbidity related to the injury. Full physiologic recovery and normal cardiac function can be expected if the patient survives. Copyright © 2011 by Lippincott Williams & Wilkins

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.

Specific α7 nicotinic acetylcholine receptor agonist ameliorates isoproterenol-induced cardiac remodelling in mice through TGF-β1/Smad3 pathway.

PubMed

Yang, Yong-Hua; Fang, Huan-Le; Zhao, Ming; Wei, Xiang-Lan; Zhang, Ning; Wang, Shun; Lu, Yi; Yu, Xiao-Jiang; Sun, Lei; He, Xi; Li, Dong-Ling; Liu, Jin-Jun; Zang, Wei-Jin

2017-12-01

It is well-accepted that inflammation plays an important role in the development of cardiac remodelling and that therapeutic approaches targeting inflammation can inhibit cardiac remodelling. Although a large amount of evidence indicates that activation of α7 nicotinic acetylcholine receptor (α7nAChR) causes an anti-inflammatory effect, the role of α7nAChR in cardiac remodelling and the underlying mechanism have not been established. To investigate the effect of the specific α7nAChR agonist, PNU282987, on cardiac remodelling induced by isoproterenol (ISO 60 mg/kg per day) in mice, the cardiomyocyte cross-sectional area (CSA) and collagen volume fraction were evaluated by hematoxylin and eosin (HE) and Masson staining, respectively. Cardiac function and ventricular wall thickness were measured by echocardiography. The protein expressions of collagen I, matrix metalloproteinase 9 (MMP-9), transforming growth factor β1 (TGF-β1), and Smad3 were analyzed by Western blot. ISO-induced cardiac hypertrophy, characterized by an increase in the heart weight/body weight ratio, CSA and ventricular wall thickness. Moreover, cardiac fibrosis indices, such as collagen volume fraction, MMP-9 and collagen I protein expression, were also increased by ISO. PNU282987 not only attenuated cardiac hypertrophy but also decreased the cardiac fibrosis induced by ISO. Furthermore, PNU282987 suppressed TGF-β1 protein expression and the phosphorylation of Smad3 induced by ISO. In conclusion, PNU282987 ameliorated the cardiac remodelling induced by ISO, which may be related to the TGF-β1/Smad3 pathway. These data imply that the α7nAChR may represent a novel therapeutic target for cardiac remodelling in many cardiovascular diseases. © 2017 John Wiley & Sons Australia, Ltd.

The role of dietary long chain fatty acids in mitochondrial structure and function. Effects on rat cardiac mitochondrial respiration.

PubMed

Clandinin, M T

1978-02-01

To evaluate the effect of dietary rapeseed oils on cardiac mitochondrial function and metabolic conservation of energy, male weanling rats derived from the Sprague-Dawley strain were fed three rations containing either 15% (w/w) soybean oil, low erucic acid rapeseed oil or a high erucic acid rapeseed oil. Cardiac mitochondria were isolated for measurement of mitochondrial respiratory functions. Pyruvate and malate plus malonate or succinate plus amytal, or alpha-ketoglutarate and malate plus malonate were utilized as substrates for oxidative phosphorylation. Net rates of state 3 oxygen uptake and therefore ATP synthesis were found to decline with chronic feeding of the 15% (w/w) oil containing diets. Significantly reduced ADP/O ratios were observed for groups fed high erucic acid rapeseed oil containing diets for 11 days. Decreased ADP/O ratios were also observed for groups fed high or low erucic acid rapeseed oils for 112 days. When pyruvate and malate plus malonate were utilized as substrates, reduced rates of ATP synthesis were observed after chronic feeding of high erucic acid rapeseed oil diets. Only prolonged feeding of low erucic acid rapeseed oils resulted in significant alterations in the efficiency of oxidative phosphorylation.

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.

Exposure to occupational air pollution and cardiac function in workers of the Esfahan Steel Industry, Iran.

PubMed

Golshahi, Jafar; Sadeghi, Masoumeh; Saqira, Mohammad; Zavar, Reihaneh; Sadeghifar, Mostafa; Roohafza, Hamidreza

2016-06-01

Air pollution is recognized as an important risk factor for cardiovascular disease. We investigated association of exposure to occupational air pollution and cardiac function in the workers of the steel industry. Fifty male workers of the agglomeration and coke-making parts of the Esfahan Steel Company were randomly selected (n = 50). Workers in the administrative parts were studied as controls (n = 50). Those with known history of hypertension, dyslipidemia, or diabetes, and active smokers were not included. Data of age, body mass index, employment duration, blood pressure, fasting blood sugar, and lipid profile were gathered. Echocardiography was performed to evaluate cardiac function. Left ventricular ejection fraction was lower in workers of the agglomeration/coke-making parts than in controls (mean difference = 5 to 5.5 %, P < 0.001). Mild right ventricular dilatation and grade I pulmonary hypertension were present in three (12 %) workers of the coke-making part, but none of the controls (P = 0.010). According to these results, occupational air pollution exposure in workers of the steel industry is associated with left heart systolic dysfunction. Possible right heart insults due to air pollution exposure warrant further investigations.

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.

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

PubMed

Liu, Zhong-wei; Wang, Jun-kui; Qiu, Chuan; Guan, Gong-chang; Liu, Xin-hong; Li, Shang-jian; Deng, Zheng-rong

2015-03-01

Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction.

PubMed

Chen, Yueqiu; Zhao, Yunfeng; Chen, Weiqian; Xie, Lincen; Zhao, Zhen-Ao; Yang, Junjie; Chen, Yihuan; Lei, Wei; Shen, Zhenya

2017-11-25

Our study aim was to evaluate the therapeutic efficacy and mechanisms of miR-133-overexpressing mesenchymal stem cells (MSCs) on acute myocardial infarction. Rat MSCs were isolated and purified by whole bone marrow adherent culturing. After transfection with the agomir or antagomir of miR-133, MSCs were collected for assay of cell vitality, apoptosis, and cell cycle progression. At the same time, exosomes were isolated from the supernatant to analyze the paracrine miR-133. For in-vivo studies, constitutive activation of miR-133 in MSCs was achieved by lentivirus-mediated miR-133 overexpression. A rat myocardial infarction model was created by ligating the left anterior descending coronary artery, while control MSCs (vector-MSCs) or miR-133-overexpressed MSCs (miR-133-MSCs) were injected into the zone around the myocardial infarction. Subsequently, myocardial function was evaluated by echocardiography on days 7 and 28 post infarction. Finally the infarcted hearts were collected on days 7 and 28 for myocardial infarct size measurement and detection of snail 1 expression. Hypoxia-induced apoptosis of MSCs obviously reduced, along with enhanced expression of total poly ADP-ribose polymerase protein, after miR-133 agomir transfection, while the apoptosis rate increased in MSCs transfected with miR-133 antagomir. However, no change in cell viability and cell-cycle distribution was observed in control, miR-133-overexpressed, and miR-133-interfered MSCs. Importantly, rats transplanted with miR-133-MSCs displayed more improved cardiac function after acute myocardial infarction, compared with those that received vector-MSC injection. Further studies indicated that cardiac expression of snail 1 was significantly repressed by adjacent miR-133-overexpressing MSCs, and both the inflammatory level and the infarct size decreased in miR-133-MSC-injected rat hearts. miR-133-MSCs obviously improved cardiac function in a rat model of myocardial infarction. Transplantation of miR-133-overexpressing MSCs provides an effective strategy for cardiac repair and modulation of cardiac-related diseases.

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.

Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

PubMed

Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Abe, Masami; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-05-26

BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

Cardiac function in children with premature ventricular contractions: the effect of omega-3 polyunsaturated fatty acid supplementation.

PubMed

Oner, Taliha; Ozdemir, Rahmi; Doksöz, Onder; Genc, Dildar B; Guven, Baris; Demirpence, Savas; Yilmazer, Murat M; Yozgat, Yilmaz; Mese, Timur; Tavli, Vedide

2018-07-01

Premature ventricular contractions are accepted as benign in structurally normal hearts. However, reversible cardiomyopathy can sometimes develop. Omega-3 polyunsaturated fatty acids have anti-arrhythmic properties in animals and humans.AimWe evaluated left ventricular function in children with premature ventricular contractions with normal cardiac anatomy and assessed the impact of omega-3 fatty acid supplementation on left ventricular function in a prospective trial. A total of 25 patients with premature ventricular contraction, with more than 2% premature ventricular contractions on 24-hour Holter electrocardiography, and 30 healthy patients were included into study. All patients underwent electrocardiography, left ventricular M-mode echocardiography, and myocardial performance index testing. Patients with premature ventricular contraction were given omega-3 fatty acids at a dose of 1 g/day for 3 months, and control echocardiography and 24-hour Holter electrocardiography were performed. Neither placebo nor omega-3 fatty acids were given to the control group. Compared with the values of the control group, the patients with premature ventricular contraction had significantly lower fractional shortening. The myocardial performance index decreased markedly in the patient groups. The mean heart rate and mean premature ventricular contraction percentage of Group 2 significantly decreased in comparison with their baseline values after the omega-3 supplementation. In conclusion, premature ventricular contractions can lead to systolic cardiac dysfunction in children. Omega-3 supplementation may improve cardiac function in children with premature ventricular contractions. This is the first study conducted in children to investigate the possible role of omega-3 fatty acid supplementation on treatment of premature ventricular contractions.

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

Hu Shunying; Chen Yundai; Li Libing

Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrastmore » echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +- 9.01 vs. 41.94 +- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +- 1303 vs. 1667 +- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +- 1084 vs. 1566 +- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.« less

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.

External validation of the Revised Cardiac Risk Index and update of its renal variable to predict 30-day risk of major cardiac complications after non-cardiac surgery: rationale and plan for analyses of the VISION study.

PubMed

Roshanov, Pavel S; Walsh, Michael; Devereaux, P J; MacNeil, S Danielle; Lam, Ngan N; Hildebrand, Ainslie M; Acedillo, Rey R; Mrkobrada, Marko; Chow, Clara K; Lee, Vincent W; Thabane, Lehana; Garg, Amit X

2017-01-09

The Revised Cardiac Risk Index (RCRI) is a popular classification system to estimate patients' risk of postoperative cardiac complications based on preoperative risk factors. Renal impairment, defined as serum creatinine >2.0 mg/dL (177 µmol/L), is a component of the RCRI. The estimated glomerular filtration rate has become accepted as a more accurate indicator of renal function. We will externally validate the RCRI in a modern cohort of patients undergoing non-cardiac surgery and update its renal component. The Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study is an international prospective cohort study. In this prespecified secondary analysis of VISION, we will test the risk estimation performance of the RCRI in ∼34 000 participants who underwent elective non-cardiac surgery between 2007 and 2013 from 29 hospitals in 15 countries. Using data from the first 20 000 eligible participants (the derivation set), we will derive an optimal threshold for dichotomising preoperative renal function quantified using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) glomerular filtration rate estimating equation in a manner that preserves the original structure of the RCRI. We will also develop a continuous risk estimating equation integrating age and CKD-Epi with existing RCRI risk factors. In the remaining (approximately) 14 000 participants, we will compare the risk estimation for cardiac complications of the original RCRI to this modified version. Cardiac complications will include 30-day non-fatal myocardial infarction, non-fatal cardiac arrest and death due to cardiac causes. We have examined an early sample to estimate the number of events and the distribution of predictors and missing data, but have not seen the validation data at the time of writing. The research ethics board at each site approved the VISION protocol prior to recruitment. We will publish our results and make our models available online at http://www.perioperativerisk.com. ClinicalTrials.gov NCT00512109. 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/.

SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function

PubMed Central

Hatcher, Jeffrey; Gu, He; Cheng, Zixi (Jack)

2016-01-01

Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2 ∙−), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions of O2 ∙− may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and ΔHR versus ΔMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function. PMID:26823951

Flexible Molybdenum Electrodes towards Designing Affinity Based Protein Biosensors.

PubMed

Kamakoti, Vikramshankar; Panneer Selvam, Anjan; Radha Shanmugam, Nandhinee; Muthukumar, Sriram; Prasad, Shalini

2016-07-18

Molybdenum electrode based flexible biosensor on porous polyamide substrates has been fabricated and tested for its functionality as a protein affinity based biosensor. The biosensor performance was evaluated using a key cardiac biomarker; cardiac Troponin-I (cTnI). Molybdenum is a transition metal and demonstrates electrochemical behavior upon interaction with an electrolyte. We have leveraged this property of molybdenum for designing an affinity based biosensor using electrochemical impedance spectroscopy. We have evaluated the feasibility of detection of cTnI in phosphate-buffered saline (PBS) and human serum (HS) by measuring impedance changes over a frequency window from 100 mHz to 1 MHz. Increasing changes to the measured impedance was correlated to the increased dose of cTnI molecules binding to the cTnI antibody functionalized molybdenum surface. We achieved cTnI detection limit of 10 pg/mL in PBS and 1 ng/mL in HS medium. The use of flexible substrates for designing the biosensor demonstrates promise for integration with a large-scale batch manufacturing process.

[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

Evaluation of concordance among three cardiac output measurement techniques in adult patients during cardiovascular surgery postoperative care.

PubMed

Muñoz, L; Velandia, A; Reyes, L E; Arevalo-Rodríguez, I; Mejía, C; Asprilla, D; Uribe, D V; Arevalo, J J

2017-12-01

The standard method for cardiac output measuring is thermodilution although it is an invasive technique. Transesophageal Echocardiography (TEE) offers a dynamic and functional alternative to thermodilution. Analyze concordance between two TEE methods and thermodilution for cardiac output assessment. Observational concordance study in cardiovascular surgery patients that required pulmonary artery catheter. TEE cardiac output measurement at both mitral annulus (MA) and left ventricle outflow tract (LVOT) were performed. Results were compared with thermodilution. Correlation was evaluated by Lin's concordance correlation coefficient and Bland-Altman analysis. Statistical analysis was undertaken in STATA 13.0. Twenty-five patients were enrolled. Fifty two percent of patients were male, median age and ejection fraction was 63 years and 35% respectively. Median thermodilution, LVOT and MA -measured cardiac output was 3.25 L/min, 3.46 L/min and 8.4 L/min respectively. Different values between thermodilution and MA measurements were found (Lin concordance=0.071; Confidence Interval 95%=-0.009 to 0.151; Spearman's correlation=0.22) as values between thermodilution and LVOT (Lin concordance=0.232; Confidence Interval 95%=-0.12 a 0.537; Spearman's correlation 0.28). Bland-Altman analysis showed greater difference between MA measurements and thermodilution (DM=-0.408; Bland-Altman Limits=-0.809 to -0.007), than the other echocardiographic findings (DM=0.007; Bland-Altman Limits=-0.441 to 0.428). Results from cardiac output measurement by doppler and 2D-TEE on both MA and LVOT do not correlate with those obtained by thermodilution. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Pathological presentation of cardiac mitochondria in a rat model for chronic kidney disease.

PubMed

Bigelman, Einat; Cohen, Lena; Aharon-Hananel, Genya; Levy, Ran; Rozenbaum, Zach; Saada, Ann; Keren, Gad; Entin-Meer, Michal

2018-01-01

Mitochondria hold crucial importance in organs with high energy demand especially the heart. We investigated whether chronic kidney disease (CKD), which eventually culminates in cardiorenal syndrome, could affect cardiac mitochondria and assessed the potential involvement of angiotensin II (AngII) in the process. Male Lewis rats underwent 5/6 nephrectomy allowing CKD development for eight months or for eleven weeks. Short-term CKD rats were administered with AngII receptor blocker (ARB). Cardiac function was assessed by echocardiography and cardiac sections were evaluated for interstitial fibrosis and cardiomyocytes' hypertrophy. Electron microscopy was used to explore the spatial organization of the cardiomyocytes. Expression levels of mitochondrial content and activity markers were tested in order to delineate the underlying mechanisms for mitochondrial pathology in the CKD setting with or without ARB administration. CKD per-se resulted in induced cardiac interstitial fibrosis and cardiomyocytes' hypertrophy combined with a marked disruption of the mitochondrial structure. Moreover, CKD led to enhanced cytochrome C leakage to the cytosol and to enhanced PARP-1 cleavage which are associated with cellular apoptosis. ARB treatment did not improve kidney function but markedly reduced left ventricular mass, cardiomyocytes' hypertrophy and interstitial fibrosis. Interestingly, ARB administration improved the spatial organization of cardiac mitochondria and reduced their increased volume compared to untreated CKD animals. Nevertheless, ARB did not improve mitochondrial content, mitochondrial biogenesis or the respiratory enzyme activity. ARB mildly upregulated protein levels of mitochondrial fusion-related proteins. CKD results in cardiac pathological changes combined with mitochondrial damage and elevated apoptotic markers. We anticipate that the increased mitochondrial volume mainly represents mitochondrial swelling that occurs during the pathological process of cardiac hypertrophy. Chronic administration of ARB may improve the pathological appearance of the heart. Further recognition of the molecular pathways leading to mitochondrial insult and appropriate intervention is of crucial importance.

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.

Pharmacological inhibition of DNA methylation attenuates pressure overload-induced cardiac hypertrophy in rats.

PubMed

Stenzig, Justus; Schneeberger, Yvonne; Löser, Alexandra; Peters, Barbara S; Schaefer, Andreas; Zhao, Rong-Rong; Ng, Shi Ling; Höppner, Grit; Geertz, Birgit; Hirt, Marc N; Tan, Wilson; Wong, Eleanor; Reichenspurner, Hermann; Foo, Roger S-Y; Eschenhagen, Thomas

2018-07-01

Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes. Young male Wistar rats were subjected to PO by transverse aortic constriction (TAC) or to sham surgery. Rats from both groups received solvent or 12.5 mg/kg body weight of the non-nucleosidic DNMT inhibitor RG108, initiated on the day of the intervention. After 4 weeks, we analysed cardiac function by MRI, fibrosis with Sirius Red staining, gene expression by RNA sequencing and qPCR, and DNA methylation by reduced representation bisulphite sequencing (RRBS). RG108 attenuated the ~70% increase in heart weight/body weight ratio of TAC over sham to 47% over sham, partially rescued reduced contractility, diminished the fibrotic response and the downregulation of a set of genes including Atp2a2 (SERCA2a) and Adrb1 (beta1-adrenoceptor). RG108 was associated with significantly lower global DNA methylation in cardiomyocytes by ~2%. The differentially methylated pathways were "cardiac hypertrophy", "cell death" and "xenobiotic metabolism signalling". Among these, "cardiac hypertrophy" was associated with significant methylation differences in the group comparison sham vs. TAC, but not significant between sham+RG108 and TAC+RG108 treatment, suggesting that RG108 partially prevented differential methylation. However, when comparing TAC and TAC+RG108, the pathway cardiac hypertrophy was not significantly differentially methylated. DNMT inhibitor treatment is associated with attenuation of cardiac hypertrophy and moderate changes in cardiomyocyte DNA methylation. The potential mechanistic link between these two effects and the role of non-myocytes need further clarification. Copyright © 2018 Elsevier Ltd. All rights reserved.

Usefulness of cardiac MRI in the prognosis and follow-up of ischemic heart disease.

PubMed

Hidalgo, A; Pons-Lladó, G

2015-01-01

Cardiac magnetic resonance imaging (MRI) is an important tool that makes it possible to evaluate patients with cardiovascular disease; in addition to infarction and alterations in myocardial perfusion, cardiac MRI is useful for evaluating other phenomena such as microvascular obstruction and ischemia. The main prognostic factors in cardiac MRI are ventricular dysfunction, necrosis in late enhancement sequences, and ischemia in stress sequences. In acute myocardial infarction, cardiac MRI can evaluate the peri-infarct zone and quantify the size of the infarct. Furthermore, cardiac MRI's ability to detect and evaluate microvascular obstruction makes it a fundamental tool for establishing the prognosis of ischemic heart disease. In patients with chronic ischemic heart disease, cardiac MRI can detect ischemia induced by pharmacological stress and can diagnose infarcts that can be missed on other techniques. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

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

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.

Randomized controlled trial on the impact of music therapy during cardiac catheterization on reactive hyperemia index and patient satisfaction: the Functional Change in Endothelium After Cardiac Catheterization, With and Without Music Therapy (FEAT) study.

PubMed

Ripley, Lindsay; Christopoulos, Georgios; Michael, Tesfaldet T; Alomar, Mohammed; Rangan, Bavana V; Roesle, Michele; Kotsia, Anna; Banerjee, Subhash; Brilakis, Emmanouil S

2014-09-01

To determine the impact of music intervention on endothelial function, hemodynamics, and patient anxiety before, during, and after cardiac catheterization. The effect of music therapy during cardiac catheterization on endothelial function and patient satisfaction has received limited study. Seventy patients undergoing elective cardiac catheterization were randomized to music therapy (n=36) or no music therapy (n=34). Peripheral arterial tonometry was performed before and after catheterization. A 6 item (24-point scale) questionnaire evaluating patient anxiety and discomfort levels was also administered after the procedure. Both study groups had similar baseline characteristics, fluoroscopy time, and contrast administration. Reactive hyperemia index (RHI) change was 0.14 ± 0.72 in the music group and 0.30 ± 0.58 in the control group (P=.35). Systolic and diastolic blood pressure (BP) changes did not significantly differ between the two groups (systolic BP change -3.3 ± 17.3 mm Hg vs -2.3 ± 19.4 mm Hg; P=.83 and diastolic BP change -1.9 ± 12.2 mm Hg vs. 2.0 ± 13.4 mm Hg; P=.23). Heart rate changes were also comparable between the two groups (-1 ± 6 beats/ min vs -1 ± 7 beats/min; P=.22). Patient satisfaction questionnaire measurements were found to be similar in patients with and without music therapy (8 [7-11] vs 9 [8-12]; P=.36). In this study, music intervention did not elicit a vasodilator response, did not lower blood pressure or heart rate, and did not relieve anxiety or stress discomfort in patients who underwent coronary angiography.

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.

Autonomic Nervous Activity and Lipid Oxidation Postexercise with Capsaicin in the Humans

PubMed Central

Yeo, Nam Hwoeh; Kang, Sunghwun

2010-01-01

This study evaluated the synergistic effects of acute exercise with capsaicin (200mg) upon the restoration of cardiac autonomic functions and depolarization- repolarization interval as well as substrate oxidation. Nine healthy males [21.9(0.8) yrs] volunteered for this study. Cardiac autonomic activity, metabolic responses, and the ECG QT intervals were continuously measured during 5 min at rest and postexercise recovery after 30 min exercise at 50% VO2max on a stationary ergometer with placebo (ECON) or capsaicin intake (ECAP), and no exercise control (NCON) were randomized. Results indicated that the HF power reflecting parasympathetic activity significantly returned to the baseline much faster during ECAP than ECON trial during postexercise [122.1 (23.2) vs. 60.2 (11.7) %, p < 0.05]. The ECAP trial significantly decreased RQ [0.79(0.02) vs. 0.85 (0.03), p < 0.05] with significantly greater fat oxidation [69.3 (6.0) vs. 49.4 (10.8) %, p < 0.05] in comparison to NCON trial during 120 min postexercise recovery without any adverse effects on cardiac electrical stability as determined by trigger-averaged ECG QT interval analyses. We suggest that capsaicin before the exercise may contribute to the improvement of cardio-protective functions and metabolic responses as one of the beneficial supplements accelerating faster restoration of autonomic activity and enhanced lipolysis during postexercise recovery without any adverse effects on cardiac electrical stability. Key points Capsaicin before exercise may contribute to the improvement of cardio-protective functions as one of the beneficial supplements accelerating faster restoration of autonomic activity Capsaicin before exercise enhanced lipolysis during postexercise recovery period Capsaicin intake does not influence cardiac electrical stability during recovery period. PMID:24149693

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.

Is plasma N-BNP a good indicator of the functional reserve of failing hearts? The FRESH-BNP study.

PubMed

Williams, Simon G; Ng, Leong L; O'Brien, Russell J; Taylor, Steve; Wright, D Jay; Tan, Lip-Bun

2004-12-01

Whether plasma N-terminal brain natriuretic peptide (N-BNP) is useful in the diagnosis of heart failure (HF) depends traditionally on whether it is as good as the putative 'gold-standard', left ventricular ejection fraction (LVEF), in indicating cardiac dysfunction. However, since HF is primarily an impairment of function of the cardiac pump, we explored the relationship between N-BNP and direct and indirect indicators of cardiac pump dysfunction. Eighty-six HF patients (mean age 56 years) with a range of LVEF's (mean 36.9+/-15.2%, range 15-66%) and 10 age-matched healthy controls were recruited into the study and had resting N-BNP measured. Cardiopulmonary exercise testing was performed to assess peak oxygen consumption (Vo(2)). A subgroup of 23 subjects underwent further exercise haemodynamic assessment to evaluate peak cardiac power output (CPO). The CHF group had significantly higher N-BNP (median [interquartile range]) levels (299 [705] fmol/ml) than the control group (7 [51] fmol/ml, P<0.005). Significant correlations between N-BNP and peak Vo(2), and N-BNP and peak CPO were observed (R> or =0.5, P<0.005). Although significant correlation was observed between N-BNP and LVEF (R=0.34, P=0.01), the correlations between LVEF and peak Vo(2) or peak CPO (all R<0.3, P>0.3) were not significant. Multivariate analysis identified plasma N-BNP and NYHA class, but not LVEF, as independent predictors of peak Vo(2). We have found that N-BNP was surprisingly good as a simple indicator of cardiac pump dysfunction. Since heart failure is an inadequacy of function, these results strongly support the notion that N-BNP is a useful blood test in estimating the extent of cardiac pump dysfunction and helpful in establishing positive diagnosis of heart failure.

Cardiac rehabilitation improves coronary endothelial function in patients with heart failure due to dilated cardiomyopathy: A positron emission tomography study.

PubMed

Legallois, Damien; Belin, Annette; Nesterov, Sergey V; Milliez, Paul; Parienti, J-J; Knuuti, Juhani; Abbas, Ahmed; Tirel, Olivier; Agostini, Denis; Manrique, Alain

2016-01-01

Endothelial dysfunction is common in patients with heart failure and is associated with poor clinical outcome. Cardiac rehabilitation is able to enhance peripheral endothelial function but its impact on coronary vasomotion remains unknown. We aimed to evaluate the effect of cardiac rehabilitation on coronary vasomotion in patients with heart failure. We prospectively enrolled 29 clinically stable heart failure patients from non-ischaemic dilated cardiomyopathy and without coronary risk factors. Myocardial blood flow was quantified using (15)-O water positron emission tomography at rest and during a cold pressor test, before and after 12 weeks of cardiac rehabilitation and optimization of medical therapy. Rest myocardial blood flow was significantly improved after the completion of rehabilitation compared to baseline (1.31 ± 0.38 mL/min/g vs. 1.16 ± 0.41 mL/min/g, p = 0.04). The endothelium-related change in myocardial blood flow from rest to cold pressor test and the percentage of myocardial blood flow increase during the cold pressor test were both significantly improved after cardiac rehabilitation (respectively from -0.03 ± 0.22 mL/min/g to 0.19 ± 0.22 mL/min/g, p < 0.001 and from 101.5 ± 16.5% to 118.3 ± 24.4%, p < 0.001). Left ventricular ejection fraction, plasma levels of brain natriuretic peptide, maximal oxygen consumption and the Minnesota Living with Heart Failure Questionnaire score were also significantly improved. The improvement was not related to uptitration of medical therapy. Coronary endothelial function is altered in patients with heart failure due to non-ischaemic dilated cardiomyopathy. In these patients, cardiac rehabilitation significantly improves coronary vasomotion. © The European Society of Cardiology 2014.

Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing cardiac effects of long-term enzyme replacement therapy.

PubMed

Messalli, G; Imbriaco, M; Avitabile, G; Russo, R; Iodice, D; Spinelli, L; Dellegrottaglie, S; Cademartiri, F; Salvatore, M; Pisani, A

2012-02-01

Anderson-Fabry disease is a multisystemic disorder of lipid metabolism secondary to X-chromosome alterations and is frequently associated with cardiac manifestations such as left ventricular (LV) hypertrophy, gradually leading to an alteration in cardiac performance. The purpose of this study was to monitor, using magnetic resonance imaging (MRI), any changes produced by enzyme replacement therapy with agalsidase beta at the cardiac level in patients with Anderson-Fabry disease. Sixteen (ten men, six women) patients with genetically confirmed Anderson-Fabry disease underwent cardiac MRI before starting enzyme replacement therapy (baseline study) and after 48 months of treatment with agalsidase beta at the dose of 1 mg/kg (follow-up study). After 48 months of treatment, a significant reduction in LV mass and wall thickness was observed: 187±59 g vs. 149±44 g, and 16±3 mm vs. 13±3 mm, respectively. A significant reduction in T2 relaxation time was noted at the level of the interventricular septum (81±3 ms vs. 67±7 ms), at the apical level (80±8 ms vs. 63±6 ms) and at the level of the lateral wall (82±8 ms vs. 63±10 ms) (p<0.05). No significant variation was observed in ejection fraction between the two studies (65±3% vs. 64±2%; p>0.05) (mean bias 1.0); however, an improvement was noted in the New York Heart Association (NYHA) class of the majority of patients (12/16) (p<0.05). In patients with Anderson-Fabry disease undergoing enzyme replacement therapy with agalsidase beta, MRI documented a significant reduction in myocardial T2 relaxation time, a significant decrease in maximal myocardial thickness and in total LV mass. MRI did not reveal significant improvements in LV global systolic function; however, improvement in NYHA functional class was noted, consistent with improved diastolic function.

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.

Cardiac tissue injury resistance during myocardial infarction at adulthood by developmental exposure to cadmium.

PubMed

Zepeda, Ramiro; Castillo, Paula; Sáez, Daniel; Llanos, Miguel N; Ronco, Ana M

2012-03-01

It has been suggested that prenatal exposure to cadmium may alter the cardiovascular function during adulthood. Using the left coronary artery ligation model of acute myocardial infarction, we studied the cardiac function of female adult offspring rats exposed to cadmium (30 ppm) during gestation. The cardiac ischemic zone in the control and cadmium-exposed groups was measured 72 h post-ligation using the TPT staining technique. Offspring from cadmium-treated dams showed a significantly smaller infarcted area compared with the control group (7.1 ± 1.5 vs. 19.6 ± 2.8%, P ≤ 0.05). We also performed echocardiographic and biochemical studies, which positively correlated with the differences observed previously. To evaluate whether the effects were associated to pre-infarct tissue damage and/or angiogenic molecules, we performed histological studies and measured the expression of vascular endothelial growth factor (VEGF), and platelet endothelial cellular adhesion molecule-1 (PECAM-1). Results revealed a higher heart vascularization in the exposed offspring that was associated with an increase in PECAM and a decrease in VEGF expression. We conclude that prenatal exposure to cadmium induces fetal adaptive responses involving changes in the expression of some cardiac angiogenic molecules resulting in long-term resistance to infarction.

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

The effect of childhood obesity on cardiac functions.

PubMed

Üner, Abdurrahman; Doğan, Murat; Epcacan, Zerrin; Epçaçan, Serdar

2014-03-01

Obesity is a metabolic disorder defined as excessive accumulation of body fat, which is made up of genetic, environmental, and hormonal factors and has various social, psychological, and medical complications. Childhood obesity is a major indicator of adult obesity. The aim of this study is to evaluate the cardiac functions via electrocardiography (ECG), echocardiography (ECHO), and treadmill test in childhood obesity. A patient group consisting of 30 obese children and a control group consisting of 30 non-obese children were included in the study. The age range was between 8 and 17 years. Anthropometric measurements, physical examination, ECG, ECHO, and treadmill test were done in all patients. P-wave dispersion (PD) was found to be statistically significantly high in obese patients. In ECHO analysis, we found that end-diastolic diameter, end-systolic diameter, left ventricle posterior wall thickness, and interventricular septum were significantly greater in obese children. In treadmill test, exercise capacity was found to be significantly lower and the hemodynamic response to exercise was found to be defective in obese children. Various cardiac structural and functional changes occur in childhood obesity and this condition includes important cardiovascular risks. PD, left ventricle end-systolic and end-diastolic diameter, left ventricle posterior wall thickness, interventricular septum thickness, exercise capacity, and hemodynamic and ECG measurements during exercise testing are useful tests to determine cardiac dysfunctions and potential arrhythmias even in early stages of childhood obesity. Early recognition and taking precautions for obesity during childhood is very important to intercept complications that will occur in adulthood.

Risk of cardiac disease and observations on lack of potential predictors by clinical history among children presenting for cardiac evaluation of mid-exertional syncope.

PubMed

Miyake, Christina Y; Motonaga, Kara S; Fischer-Colbrie, Megan E; Chen, Liyuan; Hanisch, Debra G; Balise, Raymond R; Kim, Jeffrey J; Dubin, Anne M

2016-06-01

This study aimed to evaluate the incidence of cardiac disorders among children with mid-exertional syncope evaluated by a paediatric cardiologist, determine how often a diagnosis was not established, and define potential predictors to differentiate cardiac from non-cardiac causes. Study design We carried out a single-centre, retrospective review of children who presented for cardiac evaluation due to a history of exertional syncope between 1999 and 2012. Inclusion criteria included the following: (1) age ⩽18 years; (2) mid-exertional syncope; (3) electrocardiogram, echocardiogram and an exercise stress test, electrophysiology study, or tilt test, with exception of long QT, which did not require additional testing; and (4) evaluation by a paediatric cardiologist. Mid-exertional syncope was defined as loss of consciousness in the midst of active physical activity. Patients with peri-exertional syncope immediately surrounding but not during active physical exertion were excluded. A total of 60 patients met the criteria for mid-exertional syncope; 32 (53%) were diagnosed with cardiac syncope and 28 with non-cardiac syncope. A majority of cardiac patients were diagnosed with an electrical myopathy, the most common being Long QT syndrome. In nearly half of the patients, a diagnosis could not be established or syncope was felt to be vasovagal in nature. Neither the type of exertional activity nor the symptoms or lack of symptoms occurring before, immediately preceding, and after the syncopal event differentiated those with or without a cardiac diagnosis. Children with mid-exertional syncope are at risk for cardiac disease and warrant evaluation. Reported symptoms may not differentiate benign causes from life-threatening disease.

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.

Echocardiographic assessment of cardiac disease

NASA Technical Reports Server (NTRS)

Popp, R. L.

1976-01-01

The physical principles and current applications of echocardiography in assessment of heart diseases are reviewed. Technical considerations and unresolved points relative to the use of echocardiography in various disease states are stressed. The discussion covers normal mitral valve motion, mitral stenosis, aortic regurgitation, atrial masses, mitral valve prolapse, and idiopathic hypertrophic subaortic stenosis. Other topics concern tricuspic valve abnormalities, aortic valve disease, pulmonic valve, pericardial effusion, intraventricular septal motion, and left ventricular function. The application of echocardiography to congenital heart disease diagnosis is discussed along with promising ultrasonic imaging systems. The utility of echocardiography in quantitative evaluation of cardiac disease is demonstrated.

Clinical experience with a high-performance ATM-connected DICOM archive for cardiology

NASA Astrophysics Data System (ADS)

Solomon, Harry P.

1997-05-01

A system to archive large image sets, such as cardiac cine runs, with near realtime response must address several functional and performance issues, including efficient use of a high performance network connection with standard protocols, an architecture which effectively integrates both short- and long-term mass storage devices, and a flexible data management policy which allows optimization of image distribution and retrieval strategies based on modality and site-specific operational use. Clinical experience with such as archive has allowed evaluation of these systems issues and refinement of a traffic model for cardiac angiography.

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch

PubMed Central

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M. L.; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G.

2015-01-01

Introduction Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. Methods hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. Results SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Conclusions Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment created by an aligned nanofiber patch. In this environment, these cells better approximate normal cardiac tissue compared with cells cultured on flat surface and can serve as the basis for bioengineering of an implantable cardiac patch. PMID:25993466

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch.

PubMed

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M L; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G

2015-01-01

Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment created by an aligned nanofiber patch. In this environment, these cells better approximate normal cardiac tissue compared with cells cultured on flat surface and can serve as the basis for bioengineering of an implantable cardiac patch.

p53 and Mdm2 act synergistically to maintain cardiac homeostasis and mediate cardiomyocyte cell cycle arrest through a network of microRNAs.

PubMed

Stanley-Hasnain, Shanna; Hauck, Ludger; Grothe, Daniela; Aschar-Sobbi, Roozbeh; Beca, Sanja; Butany, Jagdish; Backx, Peter H; Mak, Tak W; Billia, Filio

2017-01-01

Defining the roadblocks responsible for cell cycle arrest in adult cardiomyocytes lies at the core of developing cardiac regenerative therapies. p53 and Mdm2 are crucial mediators of cell cycle arrest in proliferative cell types, however, little is known about their function in regulating homeostasis and proliferation in terminally differentiated cell types, like cardiomyocytes. To explore this, we generated a cardiac-specific conditional deletion of p53 and Mdm2 (DKO) in adult mice. Herein we describe the development of a dilated cardiomyopathy, in the absence of cardiac hypertrophy. In addition, DKO hearts exhibited a significant increase in cardiomyocyte proliferation. Further evaluation showed that proliferation was mediated by a significant increase in Cdk2 and cyclin E with downregulation of p21 Cip1 and p27 Kip1 . Comparison of miRNA expression profiles from DKO mouse hearts and controls revealed 11 miRNAs that were downregulated in the DKO hearts and enriched for mRNA targets involved in cell cycle regulation. Knockdown of these miRNAs in neonatal rat cardiomyocytes significantly increased cytokinesis with an upregulation in the expression of crucial cell cycle regulators. These results illustrate the importance of the cooperative activities of p53 and Mdm2 in a network of miRNAs that function to impose a barrier against aberrant cardiomyocyte cell cycle re-entry to maintain cardiac homeostasis.

STRUCTURAL AND FUNCTIONAL BASES OF CARDIAC FIBRILLATION. DIFFERENCES AND SIMILARITIES BETWEEN ATRIA AND VENTRICLES

PubMed Central

Filgueiras-Rama, David; Jalife, José

2016-01-01

Evidence accumulated over the last 25 years suggests that, whether in the atria or ventricles, fibrillation may be explained by the self-organization of the cardiac electrical activity into rapidly spinning rotors giving way to spiral waves that break intermittently and result in fibrillatory conduction. The dynamics and frequency of such rotors depend on the ion channel composition, excitability and refractory properties of the tissues involved, as well as on the thickness and respective three-dimensional fiber structure of the atrial and ventricular chambers. Therefore, improving the understanding of fibrillation has required the use of multidisciplinary research approaches, including optical mapping, patch clamping and molecular biology, and the application of concepts derived from the theory of wave propagation in excitable media. Moreover, translation of such concepts to the clinic has recently opened new opportunities to apply novel mechanistic approaches to therapy, particularly during atrial fibrillation ablation. Here we review the current understanding of the manner in which the underlying myocardial structure and function influence rotor initiation and maintenance during cardiac fibrillation. We also examine relevant underlying differences and similarities between atrial fibrillation and ventricular fibrillation and evaluate the latest clinical mapping technologies used to identify rotors in either arrhythmia. Altogether, the data being discussed have significantly improved our understanding of the cellular and structural bases of cardiac fibrillation and pointed toward potentially exciting new avenues for more efficient and effective identification and therapy of the most complex cardiac arrhythmias. PMID:27042693

Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage

PubMed Central

Hadanny, A.; Golan, H.; Fishlev, G.; Bechor, Y.; Volkov, O.; Suzin, G.; Ben-Jacob, E.; Efrati, S.

2015-01-01

Abstract Purpose: Cognitive impairment may occur in 42–50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury. The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. Methods: Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. Results: The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5–7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. Conclusions: Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event. PMID:26409406

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

Translational overview of cytokine inhibition in acute myocardial infarction and chronic heart failure.

PubMed

Hartman, Minke H T; Groot, Hilde E; Leach, Irene Mateo; Karper, Jacco C; van der Harst, Pim

2018-02-15

Many cytokines are currently under investigation as potential target to improve cardiac function and outcome in the setting of acute myocardial infarction (MI) or chronic heart failure (HF). Here we aim to provide a translational overview of cytokine inhibiting therapies tested in experimental models and clinical studies. In various experimental studies, inhibition of interleukin-1 (IL-1), -6 (IL-6), -8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), CC- and CXC chemokines, and tumor necrosis factor-α (TNF-α) had beneficial effects on cardiac function and outcome. On the other hand, neutral or even detrimental results have been reported for some (IL-1, IL-6, IL-8, and MCP-1). Ambivalence of cytokine function, differences in study designs, treatment regimens and chosen endpoints hamper the translation of experimental research into clinical practice. Human studies are currently limited to IL-1β inhibition, IL-1 receptor antagonists (IL-1RA), IL-6 receptor antagonists (IL-6RA) or TNF inhibition. Despite favorable effects on cardiovascular events observed in retrospective cohort studies of rheumatoid arthritis patients treated with TNF inhibition or IL-1RA, most prospective studies reported disappointing and inconsistent results. Smaller studies (n < 100) generally reported favorable results of anticytokine therapy on cardiac function, but only one of the larger studies (n > 100) evaluating IL-1β inhibition presented positive results on outcome. In conclusion, of the 10 anticytokine therapies tested in animals models beneficial effects have been reported in at least one setting. In larger clinical studies, findings were unsatisfactory in all but one. Many anticytokine therapies with promising animal experimental data continue to require further evaluation in humans. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

IMPORTANCE OF INTEGRATED MANAGEMENT SYSTEM APPLIED IN HEALTH ESTABLISHMENTS IN ORDER TO RAISE TREATMENT QUALITY.

PubMed

Dodić, Biljana; Miljković, Tatjana; Bjelobrk, Marija; Cemerlic Ađić, Nada; Ađić, Filip; Dodić, Slobodan

2016-01-01

The term "management" is best characterized as "managing" economic or social processes to achieve objectives through a rational use of material and immaterial resources by applying the principles, functions, and management methods. This study has been aimed at evaluating the value of an integrated quality management system implemented at the Institute of Cardiovascular Diseases of Vojvodina to improve the quality of treatment. In the period from 2008 to 2010 about 40 employees from the Institute of Cardiovascular Diseases of Vojvodina attended various courses given by the lecturers of the Faculty of Technical Sciences, where the function and significance of the "International Standards Organization" were explained, after which standards of interest were implemented at the Institute of Cardiovascular Diseases of Vojvodina. The Department of Cardiology has introduced 11 cardiac procedures with 5 special instructions, 14 general procedures, and 7 specific procedures with 2 instructions. The Department of Cardiac Surgery has introduced 7 procedures to be implemented. The "Vojvodina score" model was put into practice for the perioperative evaluation of cardiac surgery risk. During 2014, the Institute of Cardiovascular Diseases ofVojvodina obtained accreditation for the period of 7 years. The integrated quality management system must be applied in order to achieve a high level of health care in the shortest possible time and with the least possible consumption of material and human resources. The application of this system in practice gives a realistic insight into the working processes and facilitates their functioning. It demands and requires constant monitoring of the system efficiency along with continuous changes and improvements of all elements of the working processes and functional units.

One-year renal and cardiac effects of bisoprolol versus losartan in recently diagnosed hypertensive patients: a randomized, double-blind study.

PubMed

Parrinello, Gaspare; Paterna, Salvatore; Torres, Daniele; Di Pasquale, Pietro; Mezzero, Manuela; La Rocca, Gabriella; Cardillo, Mauro; Trapanese, Caterina; Caradonna, Mario; Licata, Giuseppe

2009-01-01

Hypertension is a significant cause of chronic renal injury and its effective treatment is capable of reducing the rate of renal failure. beta-Adrenoceptor antagonists (beta-blockers) have been reported to induce a deterioration in renal function, while several data have indicated a renoprotective effect of treatment with the angiotensin II type 1 receptor antagonist losartan. Previous studies of the interaction between the selective beta(1)-blocker bisoprolol and kidney function were performed only for short- and medium-term periods. The aim of this study was to compare the antihypertensive efficacy and renal and cardiac haemodynamic effects of bisoprolol with those of losartan over a 1-year time period in patients with essential hypertension. Seventy-two patients (40 males) with recently diagnosed uncomplicated (European Society of Hypertension [ESH] criteria stage 1-2) hypertension (mean +/- SD age 52 +/- 12 years) were enrolled in the study. After a run-in period of 14 days on placebo, the patients were randomized in a double-blind, prospective study to receive either bisoprolol 5 mg or losartan 50 mg, administered once daily for 1 year. At recruitment and 12 months after treatment, cardiac output and renal haemodynamics and function were evaluated by echocardiography and radionuclide studies, respectively. There were no significant differences in baseline clinical data, including glomerular filtration rate and blood pressure, between the two treatment groups. At 1 year, blood pressure had decreased significantly (p < 0.001) with both treatments, and heart rate was reduced only in the group taking bisoprolol. The long-term effects on renal haemodynamics and cardiac function were similar with both drugs, the only change being a significant reduction in the filtration fraction for each group. These data suggest that both bisoprolol and losartan are effective agents for the treatment of patients with recently diagnosed ESH stage 1-2 hypertension. Over a 1-year period, both agents maintained good renal and cardiac performance and haemodynamics.

Transition from metabolic adaptation to maladaptation of the heart in obesity: role of apelin.

PubMed

Alfarano, C; Foussal, C; Lairez, O; Calise, D; Attané, C; Anesia, R; Daviaud, D; Wanecq, E; Parini, A; Valet, P; Kunduzova, O

2015-02-01

Impaired energy metabolism is the defining characteristic of obesity-related heart failure. The adipocyte-derived peptide apelin has a role in the regulation of cardiovascular and metabolic homeostasis and may contribute to the link between obesity, energy metabolism and cardiac function. Here we investigate the role of apelin in the transition from metabolic adaptation to maladaptation of the heart in obese state. Adult male C57BL/6J, apelin knock-out (KO) or wild-type mice were fed a high-fat diet (HFD) for 18 weeks. To induce heart failure, mice were subjected to pressure overload after 18 weeks of HFD. Long-term effects of apelin on fatty acid (FA) oxidation, glucose metabolism, cardiac function and mitochondrial changes were evaluated in HFD-fed mice after 4 weeks of pressure overload. Cardiomyocytes from HFD-fed mice were isolated for analysis of metabolic responses. In HFD-fed mice, pressure overload-induced transition from hypertrophy to heart failure is associated with reduced FA utilization (P<0.05), accelerated glucose oxidation (P<0.05) and mitochondrial damage. Treatment of HFD-fed mice with apelin for 4 weeks prevented pressure overload-induced decline in FA metabolism (P<0.05) and mitochondrial defects. Furthermore, apelin treatment lowered fasting plasma glucose (P<0.01), improved glucose tolerance (P<0.05) and preserved cardiac function (P<0.05) in HFD-fed mice subjected to pressure overload. In apelin KO HFD-fed mice, spontaneous cardiac dysfunction is associated with reduced FA oxidation (P<0.001) and increased glucose oxidation (P<0.05). In isolated cardiomyocytes, apelin stimulated FA oxidation in a dose-dependent manner and this effect was prevented by small interfering RNA sirtuin 3 knockdown. These data suggest that obesity-related decline in cardiac function is associated with defective myocardial energy metabolism and mitochondrial abnormalities. Furthermore, our work points for therapeutic potential of apelin to prevent myocardial metabolic abnormalities in heart failure paired with obesity.

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.

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

N-Terminal Pro-B-type Natriuretic Peptide Is Useful to Predict Cardiac Complications Following Lung Resection Surgery

PubMed Central

Lee, Chang Young; Bae, Mi Kyung; Lee, Jin Gu; Kim, Kwan-Wook; Park, In Kyu

2011-01-01

Background Cardiovascular complications are major causes of morbidity and mortality following non-cardiac thoracic operations. Recent studies have demonstrated that elevation of N-Terminal Pro-B-type natriuretic peptide (NT-proBNP) levels can predict cardiac complications following non-cardiac major surgery as well as cardiac surgery. However, there is little information on the correlation between lung resection surgery and NT-proBNP levels. We evaluated the role of NT-proBNP as a potential marker for the risk stratification of cardiac complications following lung resection surgery. Material and Methods Prospectively collected data of 98 patients, who underwent elective lung resection from August 2007 to February 2008, were analyzed. Postoperative adverse cardiac events were categorized as myocardial injury, ECG evidence of ischemia or arrhythmia, heart failure, or cardiac death. Results Postoperative cardiac complications were documented in 9 patients (9/98, 9.2%): Atrial fibrillation in 3, ECG-evidenced ischemia in 2 and heart failure in 4. Preoperative median NT-proBNP levels was significantly higher in patients who developed postoperative cardiac complications than in the rest (200.2 ng/L versus 45.0 ng/L, p=0.009). NT-proBNP levels predicted adverse cardiac events with an area under the receiver operating characteristic curve of 0.76 [95% confidence interval (CI) 0.545~0.988, p=0.01]. A preoperative NT-proBNP value of 160 ng/L was found to be the best cut-off value for detecting postoperative cardiac complication with a positive predictive value of 0.857 and a negative predictive value of 0.978. Other factors related to cardiac complications by univariate analysis were a higher American Society of Anesthesiologists grade, a higher NYHA functional class and a history of hypertension. In multivariate analysis, however, high preoperative NT-proBNP level (>160 ng/L) only remained significant. Conclusion An elevated preoperative NT-proBNP level is identified as an independent predictor of cardiac complications following lung resection surgery. PMID:22263123

Role of Myofibril-Inducing RNA in cardiac TnT expression in developing Mexican axolotl

PubMed Central

Sferrazza, Gian-Franco; Zhang, Chi; Jia, Pingping; Lemanski, Sharon L.; Athauda, Gagani; Stassi, Alyssa; Halager, Kristine; Maier, Jennifer A.; Rueda-de-Leon, Elena; Gupta, Amit; Dube, Syamalima; Huang, Xupei; Prentice, Howard M.; Dube, Dipak K.; Lemanski, Larry F.

2007-01-01

The Mexican axolotl, Ambystoma mexicanum, has been a useful animal model to study heart development and cardiac myofibrillogenesis. A naturally-occurring recessive mutant, gene “c”, for cardiac non-function in the Mexican axolotl causes a failure of myofibrillogenesis due to a lack of tropomyosin expression in homozygous mutant (c/c) embryonic hearts.. Myofibril-Inducing RNA (MIR) rescues mutant hearts in vitro by promoting tropomyosin expression and myofibril formation thereafter. We have studied the effect of MIR on the expression of various isoforms of cardiac Troponin-T (cTnT), a component of the thin filament that binds with tropomyosin. Four alternatively spliced cTnT isoforms have been characterized from developing axolotl heart. The expression of various cTnT isoforms in normal, mutant, and mutant hearts corrected with MIR, is evaluated by real-time RT-PCR using isoform specific primer pairs; MIR affects the total transcription as well as the splicing of the cTnT in axolotl heart PMID:17408593

Acute effects of firefighting on cardiac performance.

PubMed

Fernhall, Bo; Fahs, Christopher A; Horn, Gavin; Rowland, Thomas; Smith, Denise

2012-02-01

This study examined standard echocardiographic measures of cardiac size and performance in response to a 3-h firefighting training exercise. Forty experienced male personnel completed a standardized 3 h live firefighting exercise. Before and after the firefighting activities, participants were weighed, height, heart rate, blood pressure and blood samples were obtained, and echocardiographic measurements were made. Firefighting produced significant decreases in left ventricular diastolic dimension, stroke volume, fractional shortening, and mitral E velocity, tachycardia, a rise in core temperature, and a reduction in calculated plasma volume. On tissue Doppler imaging, there were no changes in systolic contractile function, but a decreased lateral wall diastolic velocity was observed. These findings show that 3 h of live firefighting produced cardiac changes consistent with cardiac fatigue, coupled with a decrease in systemic arterial compliance. These data show that live firefighting produces significant cardiovascular changes and future work is needed to evaluate if these changes are related to the increase in cardiovascular risk during live firefighting.

Audit of availability and distribution of paediatric cardiology services and facilities in Nigeria

PubMed Central

Ekure, Ekanem N; Sadoh, Wilson E; Bode-Thomas, Fidelia; Yilgwan, Christopher S; Orogade, Adeola A; Animasahun, Adeola B; Ogunkunle, Oluwatoyin O; Omokhodion, Samuel I; Babaniyi, Iretiola; Anah, Maxwell U; Otaigbe, Barbara E; Olowu, Adebiyi; Okpokowuruk, Frances; Maduka, Ogechi C; Onakpoya, Uvie U; Adiele, Daberechi K; Sani, Usman. M; Asani, Mustapha; Daniels, Queennette; Uzodimma, Chinyere C; Duru, Chika O; Abdulkadir, Mohammad B; Afolabi, Joseph K; Okeniyi, John A

2017-01-01

Summary Background Paediatric cardiac services in Nigeria have been perceived to be inadequate but no formal documentation of availability and distribution of facilities and services has been done. Objective: To evaluate and document the currently available paediatric cardiac services in Nigeria. Methods In this questionnaire-based, cross-sectional descriptive study, an audit was undertaken from January 2010 to December 2014, of the personnel and infrastructure, with their distributions according to geopolitical zones of Nigeria. Results Forty-eight centres participated in the study, with 33 paediatric cardiologists and 31 cardiac surgeons. Echocardiography, electrocardiography and pulse oximetry were available in 45 (93.8%) centres while paediatric intensive care units were in 23 (47.9%). Open-heart surgery was performed in six (12.5%) centres. South-West zone had the majority of centres (20; 41.7%). Conclusions Available paediatric cardiac services in Nigeria are grossly inadequate and poorly distributed. Efforts should be intensified to upgrade existing facilities, establish new and functional centres, and train personnel. PMID:27701490

Audit of availability and distribution of paediatric cardiology services and facilities in Nigeria.

PubMed

Ekure, Ekanem N; Sadoh, Wilson E; Bode-Thomas, Fidelia; Orogade, Adeola A; Animasahun, Adeola B; Ogunkunle, Oluwatoyin O; Babaniyi, Iretiola; Anah, Maxwell U; Otaigbe, Barbara E; Olowu, Adebiyi; Okpokowuruk, Frances; Omokhodion, Samuel I; Maduka, Ogechi C; Onakpoya, Uvie U; Adiele, Daberechi K; Sani, Usman M; Asani, Mustapha; Yilgwan, Christopher S; Daniels, Queennette; Uzodimma, Chinyere C; Duru, Chika O; Abdulkadir, Mohammad B; Afolabi, Joseph K; Okeniyi, John A

Paediatric cardiac services in Nigeria have been perceived to be inadequate but no formal documentation of availability and distribution of facilities and services has been done. To evaluate and document the currently available paediatric cardiac services in Nigeria. In this questionnaire-based, cross-sectional descriptive study, an audit was undertaken from January 2010 to December 2014, of the personnel and infrastructure, with their distributions according to geopolitical zones of Nigeria. Forty-eight centres participated in the study, with 33 paediatric cardiologists and 31 cardiac surgeons. Echocardiography, electrocardiography and pulse oximetry were available in 45 (93.8%) centres while paediatric intensive care units were in 23 (47.9%). Open-heart surgery was performed in six (12.5%) centres. South-West zone had the majority of centres (20; 41.7%). Available paediatric cardiac services in Nigeria are grossly inadequate and poorly distributed. Efforts should be intensified to upgrade existing facilities, establish new and functional centres, and train personnel.

Cardio-oncology/onco-cardiology.

PubMed

Hong, Robert A; Iimura, Takeshi; Sumida, Kenneth N; Eager, Robert M

2010-12-01

An understanding of onco-cardiology or cardio-oncology is critical for the effective care of cancer patients. Virtually all antineoplastic agents are associated with cardiotoxicity, which can be divided into 5 categories: direct cytotoxic effects of chemotherapy and associated cardiac systolic dysfunction, cardiac ischemia, arrhythmias, pericarditis, and chemotherapy-induced repolarization abnormalities. Radiation therapy can also lead to coronary artery disease and fibrotic changes to the valves, pericardium, and myocardium. All patients being considered for chemotherapy, especially those who have prior cardiac history, should undergo detailed cardiovascular evaluation to optimize the treatment. Serial assessment of left ventricular systolic function and cardiac biomarkers might also be considered in selected patient populations. Cardiotoxic effects of chemotherapy might be decreased by the concurrent use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Antiplatelet or anticoagulation therapy might be considered in patients with a potential hypercoagulable state associated with chemotherapy or cancer. Open dialogue between both cardiologists and oncologists will be required for optimal patient care. Copyright © 2010 Wiley Periodicals, Inc.

Sirtuin 1 protects the aging heart from contractile dysfunction mediated through the inhibition of endoplasmic reticulum stress-mediated apoptosis in cardiac-specific Sirtuin 1 knockout mouse model.

PubMed

Hsu, Yu-Juei; Hsu, Shih-Che; Hsu, Chiao-Po; Chen, Yen-Hui; Chang, Yung-Lung; Sadoshima, Junichi; Huang, Shih-Ming; Tsai, Chien-Sung; Lin, Chih-Yuan

2017-02-01

The longevity regulator Sirtuin 1 is an NAD + -dependent histone deacetylase that regulates endoplasmic reticulum stress and influences cardiomyocyte apoptosis during cardiac contractile dysfunction induced by aging. The mechanism underlying Sirtuin 1 function in cardiac contractile dysfunction related to aging has not been completely elucidated. We evaluated cardiac contractile function, endoplasmic reticulum stress, apoptosis, and oxidative stress in 6- and 12month-old cardiac-specific Sirtuin 1 knockout (Sirt1 -/- ) and control (Sirt1 f/f ) mice using western blotting and immunohistochemistry. Mice were injected with a protein disulphide isomerase inhibitor. For in vitro analysis, cultured H9c2 cardiomyocytes were exposed to either a Sirtuin 1 inhibitor or activator, with or without a mitochondrial inhibitor, to evaluate the effects of Sirtuin 1 on endoplasmic reticulum stress, nitric oxide synthase expression, and apoptosis. The effects of protein disulphide isomerase inhibition on oxidative stress and ER stress-related apoptosis were also investigated. Compared with 6-month-old Sirt1 f/f mice, marked impaired contractility was observed in 12-month-old Sirt1 -/- mice. These findings were consistent with increased endoplasmic reticulum stress and apoptosis in the myocardium. Measures of oxidative stress and nitric oxide synthase expression were significantly higher in Sirt1 -/- mice compared with those in Sirt1 f/f mice at 6months. In vitro experiments revealed increased endoplasmic reticulum stress-mediated apoptosis in H9c2 cardiomyocytes treated with a Sirtuin 1 inhibitor; the effects were ameliorated by a Sirtuin 1 activator. Moreover, consistent with the in vitro findings, impaired cardiac contractility was demonstrated in Sirt1 -/- mice injected with a protein disulphide isomerase inhibitor. The present study demonstrates that the aging heart is characterized by contractile dysfunction associated with increased oxidative stress and endoplasmic reticulum stress and Sirtuin 1 might have the ability to protect the aging hearts from the inhibition of endoplasmic reticulum-mediated apoptosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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

ECG telemetry in conscious guinea pigs.

PubMed

Ruppert, Sabine; Vormberge, Thomas; Igl, Bernd-Wolfgang; Hoffmann, Michael

2016-01-01

During preclinical drug development, monitoring of the electrocardiogram (ECG) is an important part of cardiac safety assessment. To detect potential pro-arrhythmic liabilities of a drug candidate and for internal decision-making during early stage drug development an in vivo model in small animals with translatability to human cardiac function is required. Over the last years, modifications/improvements regarding animal housing, ECG electrode placement, and data evaluation have been introduced into an established model for ECG recordings using telemetry in conscious, freely moving guinea pigs. Pharmacological validation using selected reference compounds affecting different mechanisms relevant for cardiac electrophysiology (quinidine, flecainide, atenolol, dl-sotalol, dofetilide, nifedipine, moxifloxacin) was conducted and findings were compared with results obtained in telemetered Beagle dogs. Under standardized conditions, reliable ECG data with low variability allowing largely automated evaluation were obtained from the telemetered guinea pig model. The model is sensitive to compounds blocking cardiac sodium channels, hERG K(+) channels and calcium channels, and appears to be even more sensitive to β-blockers as observed in dogs at rest. QT interval correction according to Bazett and Sarma appears to be appropriate methods in conscious guinea pigs. Overall, the telemetered guinea pig is a suitable model for the conduct of early stage preclinical ECG assessment. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker

PubMed Central

2013-01-01

Background Diabetic cardiomyopathy (DCM) is defined as structural and functional changes in the myocardium due to metabolic and cellular abnormalities induced by diabetes mellitus (DM). The impact of prediabetic conditions on the cardiac tissue remains to be elucidated. The goal of this study was to elucidate whether cardiac dysfunction is already present in a state of prediabetes, in the presence of insulin resistance, and to unravel the underlying mechanisms, in a rat model without obesity and hypertension as confounding factors. Methods Two groups of 16-week-old Wistar rats were tested during a 9 week protocol: high sucrose (HSu) diet group (n = 7) – rats receiving 35% of sucrose in drinking water vs the vehicle control group (n = 7). The animal model was characterized in terms of body weight (BW) and the glycemic, insulinemic and lipidic profiles. The following parameters were assessed to evaluate possible early cardiac alterations and underlying mechanisms: blood pressure, heart rate, heart and left ventricle (LV) trophism indexes, as well as the serum and tissue protein and/or the mRNA expression of markers for fibrosis, hypertrophy, proliferation, apoptosis, angiogenesis, endothelial function, inflammation and oxidative stress. Results The HSu-treated rats presented normal fasting plasma glucose (FPG) but impaired glucose tolerance (IGT), accompanied by hyperinsulinemia and insulin resistance (P < 0.01), confirming this rat model as prediabetic. Furthermore, although hypertriglyceridemia (P < 0.05) was observed, obesity and hypertension were absent. Regarding the impact of the HSu diet on the cardiac tissue, our results indicated that 9 weeks of treatment might be associated with initial cardiac changes, as suggested by the increased LV weight/BW ratio (P < 0.01) and a remarkable brain natriuretic peptide (BNP) mRNA overexpression (P < 0.01), together with a marked trend for an upregulation of other important mediators of fibrosis, hypertrophy, angiogenesis and endothelial lesions, as well as oxidative stress. The inflammatory and apoptotic markers measured were unchanged. Conclusions This animal model of prediabetes/insulin resistance could be an important tool to evaluate the early cardiac impact of dysmetabolism (hyperinsulinemia and impaired glucose tolerance with fasting normoglycemia), without confounding factors such as obesity and hypertension. Left ventricle hypertrophy is already present and brain natriuretic peptide seems to be the best early marker for this condition. PMID:23497124

AMP-Dependent Kinase and Autophagic Flux are Involved in Aldehyde Dehydrogenase 2-Offered Protection against Cardiac Toxicity of Ethanol

PubMed Central

Ge, Wei; Guo, Rui; Ren, Jun

2011-01-01

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) alleviates ethanol toxicity although the precise mechanism is unclear. This study was designed to evaluate the effect of ALDH2 on ethanol-induced myocardial damage with a focus on autophagy. Wild-type FVB and transgenic mice overexpressing ALDH2 were challenged with ethanol (3 g/kg/d, i.p.) for 3 days and cardiac mechanical function was assessed using the echocardiographic and IonOptix systems. Western blot analysis was used to evaluate essential autophagy markers, Akt and AMPK and their downstream signaling mTOR. Ethanol challenge altered cardiac geometry and function evidenced by enlarged ventricular end systolic and diastolic diameters, decreased cell shortening and intracellular Ca2+ rise, prolonged relengthening and intracellular Ca2+ decay, as well as reduced SERCA Ca2+ uptake, the effects of which were mitigated by ALDH2. Ethanol challenge facilitated myocardial autophagy as evidenced by enhanced expression of Beclin, ATG7 and LC3B II, as well as mTOR dephosphorylation, which was alleviated by ALDH2. Ethanol challenge-induced cardiac defect and apoptosis were reversed by the ALDH-2 agonist Alda-1, the autophagy inhibitor 3-MA, and the AMPK inhibitor compound C whereas the autophagy inducer rapamycin and the AMPK activator AICAR mimicked or exacerbated ethanol-induced cell injury. Ethanol promoted or suppressed phosphorylation of AMPK and Akt, respectively, in FVB but not ALDH2 murine hearts. Moreover, AICAR nullified Alda-1-induced protection against ethanol-triggered autophagic and functional changes. Ethanol increased GFP-LC3 puncta in H9c2 cells, the effect of which was ablated by Alda-1 and 3-MA. Lysosomal inhibition using bafilomycin A1, E64D and pepstatin A obliterated Alda-1- but not ethanol-induced responses in GFP-LC3 puncta. Our results suggested that ALDH2 protects against ethanol toxicity through altered Akt and AMPK signaling and regulation of autophagic flux. PMID:21871561

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.

78 FR 26794 - Prospective Grant of Start-Up Exclusive Evaluation Option License Agreement: Gene Therapy and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-08

...-Up Exclusive Evaluation Option License Agreement: Gene Therapy and Cell-Based Therapy for Cardiac... the field of use may be limited to ``Gene therapy and cell-based therapy for cardiac arrhythmias in...\\2+\\-activated adenylyl cyclase, as well as cardiac cells or cardiac-like cells derived from...

Uptake of Predictive Genetic Testing and Cardiac Evaluation for Children at Risk for an Inherited Arrhythmia or Cardiomyopathy.

PubMed

Christian, Susan; Atallah, Joseph; Clegg, Robin; Giuffre, Michael; Huculak, Cathleen; Dzwiniel, Tara; Parboosingh, Jillian; Taylor, Sherryl; Somerville, Martin

2018-02-01

Predictive genetic testing in minors should be considered when clinical intervention is available. Children who carry a pathogenic variant for an inherited arrhythmia or cardiomyopathy require regular cardiac screening and may be prescribed medication and/or be told to modify their physical activity. Medical genetics and pediatric cardiology charts were reviewed to identify factors associated with uptake of genetic testing and cardiac evaluation for children at risk for long QT syndrome, hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. The data collected included genetic diagnosis, clinical symptoms in the carrier parent, number of children under 18 years of age, age of children, family history of sudden cardiac arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each child. We identified 97 at risk children from 58 families found to carry a pathogenic variant for one of these conditions. Sixty six percent of the families pursued genetic testing and 73% underwent cardiac screening when it was recommended. Declining predictive genetic testing was significantly associated with genetic specialist recommendation (p < 0.001) and having an asymptomatic carrier father (p = 0.006). Cardiac evaluation was significantly associated with uptake of genetic testing (p = 0.007). This study provides a greater understanding of factors associated with uptake of genetic testing and cardiac evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It also identifies a need to educate families about the importance of cardiac evaluation even in the absence of genetic testing.

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.

Infarct characterization using CT

PubMed Central

Toia, Patrizia; Maffei, Erica; Cademartiri, Filippo; Lagalla, Roberto; Midiri, Massimo

2017-01-01

Myocardial infarction (MI) is a major cause of death and disability worldwide. The incidence is not expected to diminish, despite better prevention, diagnosis and treatment, because of the ageing population in industrialized countries and unhealthy lifestyles in developing countries. Nowadays it is highly requested an imaging tool able to evaluate MI and viability. Technology improvements determined an expansion of clinical indications from coronary plaque evaluation to functional applications (perfusion, ischemia and viability after MI) integrating additional phases and information in the mainstream examination. Cardiac computed tomography (CCT) and cardiac MR (CMR) employ different contrast media, but may characterize MI with overlapping imaging findings due to the similar kinetics and tissue distribution of gadolinium and iodinated contrast media. CCT may detect first-pass perfusion defects, dynamic perfusion after pharmacological stress, and delayed enhancement (DE) of non-viable territories. PMID:28540212

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

Myocardial protection using diadenosine tetraphosphate with pharmacological preconditioning.

PubMed

Ahmet, I; Sawa, Y; Nishimura, M; Yamaguchi, T; Kitakaze, M; Matsuda, H

2000-09-01

We have reported a similar cardioprotective effect and mechanism of diadenosine tetraphosphate (AP4A) and ischemic preconditioning in rat hearts. In this study, the applicability of AP4A administration to cardiac surgery was tested by using a canine cardiopulmonary bypass model. Hearts underwent 60 minutes of cardioplegic arrest (34 degrees C) by a single dose of cardioplegia. Cardioplegia contained either AP4A (40 micromol/L; n = 6) or saline (n = 6). Beagles were weaned from cardiopulmonary bypass 30 minutes after reperfusion, and left ventricular function was evaluated after another 30 minutes by using the cardiac loop analysis system. Administration of AP4A significantly improved the postischemic recovery of cardiac function and reduced the leakage of serum creatine kinase compared with saline. Systemic vascular resistance, mean aortic blood pressure, and the electrocardiographic indices were not significantly altered by AP4A administration. Administration of AP4A was cardioprotective without apparent adverse effects. Because the cardioprotective mechanism may be similar to that of ischemic preconditioning, the addition of AP4A into cardioplegia may be a novel safe method for clinical application of preconditioning cardioprotection.

The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

PubMed Central

Kim, Junhwan; Perales Villarroel, José Paul; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W.; Becker, Lance B.

2016-01-01

Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest. PMID:26770657

The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

PubMed

Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

2016-01-01

Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

Vitamin D attenuates pressure overload-induced cardiac remodeling and dysfunction in mice.

PubMed

Zhang, Liang; Yan, Xiao; Zhang, Yun-Long; Bai, Jie; Hidru, Tesfaldet Habtemariam; Wang, Qing-Shan; Li, Hui-Hua

2018-04-01

Vitamin D (VD) and its analogues play critical roles in metabolic and cardiovascular diseases. Recent studies have demonstrated that VD exerts a protective role in cardiovascular diseases. However, the beneficial effect of VD on pressure overload-induced cardiac remodeling and dysfunction and its underlying mechanisms are not fully elucidated. In this study, cardiac dysfunction and hypertrophic remodeling in mice were induced by pressure overload. Cardiac function was evaluated by echocardiography, and myocardial histology was detected by H&E and Masson's trichrome staining. Cardiomyocyte size was detected by wheat germ agglutinin staining. The protein levels of signaling mediators were examined by western blotting while mRNA expression of hypertrophic and fibrotic markers was examined by qPCR analysis. Oxidative stress was detected by dihydroethidine staining. Our results showed that administration of VD3 significantly ameliorates pressure overload-induced contractile dysfunction, cardiac hypertrophy, fibrosis and inflammation in mice. In addition, VD3 treatment also markedly inhibited cardiac oxidative stress and apoptosis. Moreover, protein levels of calcineurin A, ERK1/2, AKT, TGF-β, GRP78, cATF6, and CHOP were significantly reduced whereas SERCA2 level was upregulated in the VD3-treated hearts compared with control. These results suggest that VD3 attenuates cardiac remodeling and dysfunction induced by pressure overload, and this protective effect is associated with inhibition of multiple signaling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

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.

Cardiac oxidative stress following maternal separation stress was mitigated following adolescent voluntary exercise in adult male rat.

PubMed

Sahafi, Ehtramolsadat; Peeri, Maghsoud; Hosseini, Mir-Jamal; Azarbyjani, Mohammad Ali

2018-01-01

Early life stress (ELS) is known as a risk factor for the development of depression and its associated comorbidities, such as cardiomyopathy in depressed patients. Mitochondrial dysfunction plays a critical role in the pathophysiology of depression and cardiovascular diseases. Evidence indicates that regular physical activity has therapeutic effects on both mood and cardiovascular disorders. Therefore, the voluntary running wheel exercise (RW) during adolescence may be able to attenuate the negative impact of maternal separation stress (MS) as a valid animal model of depression on the behavior and cardiac mitochondrial function of adult rats. To do this, we applied MS to rat pups by separating them from their mothers for 180min during the postnatal day (PND) 2 to PND 14. Next, the animals were randomly divided into different treatment groups (fluoxetine [FLX] and RW) and received the treatments during adolescence, between PND 28 to PND 60. Then, we evaluated the effects of MS on the rat behaviors test, and finally, we assessed reactive oxygen species, mitochondrial glutathione, ATP and cytochrome c release in the cardiac tissue of animals. Our results showed that depressive-like behaviors following MS in adult male rats were associated with oxidative stress in cardiac tissue. Further, we found that treating animals with chronic FLX or RW during adolescence improved animal's behavior as well as cardiac mitochondrial function. The results of this study highlight the importance of adolescence as a period during which treating animals with non-pharmacological agents has significant protective effects against the negative influence of ELS on mood and cardiac energy hemostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function

PubMed Central

Zhang, Yingmei; Yuan, Ming; Bradley, Katherine M.; Dong, Feng; Anversa, Piero; Ren, Jun

2012-01-01

Obesity is often associated with reduced plasma IGF-1 levels, oxidative stress, mitochondrial damage and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high fat diet-induced oxidative, myocardial, geometric and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low (10%) or high fat (45%) diet to induce obesity. High fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin-6, insulin and triglyceride as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end systolic and diastolic diameter, increased wall thickness, and cardiac hypertrophy in high fat-fed FVB mice. High fat diet promoted ROS generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca2+ dysregulation, including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, and dampened intracellular Ca2+ rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor, post-receptor signaling molecules IRS-1 (tyrosine/serine phosphorylation), Akt, GSK3β, Foxo3a, mTOR, as well as downregulated expression of mitochondrial proteins PPARγ coactivator 1α (PGC1α) and UCP-2. Intriguingly, IGF-1 mitigated high fat diet feeding-induced alterations in ROS, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca2+ handling and insulin signaling, but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly due to preserved cell survival, mitochondrial function and insulin signaling. PMID:22275536

Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy

NASA Technical Reports Server (NTRS)

Mathur, A. B.; Collinsworth, A. M.; Reichert, W. M.; Kraus, W. E.; Truskey, G. A.

2001-01-01

This study evaluated the hypothesis that, due to functional and structural differences, the apparent elastic modulus and viscous behavior of cardiac and skeletal muscle and vascular endothelium would differ. To accurately determine the elastic modulus, the contribution of probe velocity, indentation depth, and the assumed shape of the probe were examined. Hysteresis was observed at high indentation velocities arising from viscous effects. Irreversible deformation was not observed for endothelial cells and hysteresis was negligible below 1 microm/s. For skeletal muscle and cardiac muscle cells, hysteresis was negligible below 0.25 microm/s. Viscous dissipation for endothelial and cardiac muscle cells was higher than for skeletal muscle cells. The calculated elastic modulus was most sensitive to the assumed probe geometry for the first 60 nm of indentation for the three cell types. Modeling the probe as a blunt cone-spherical cap resulted in variation in elastic modulus with indentation depth that was less than that calculated by treating the probe as a conical tip. Substrate contributions were negligible since the elastic modulus reached a steady value for indentations above 60 nm and the probe never indented more than 10% of the cell thickness. Cardiac cells were the stiffest (100.3+/-10.7 kPa), the skeletal muscle cells were intermediate (24.7+/-3.5 kPa), and the endothelial cells were the softest with a range of elastic moduli (1.4+/-0.1 to 6.8+/-0.4 kPa) depending on the location of the cell surface tested. Cardiac and skeletal muscle exhibited nonlinear elastic behavior. These passive mechanical properties are generally consistent with the function of these different cell types.

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.

Task-related changes in degree centrality and local coherence of the posterior cingulate cortex after major cardiac surgery in older adults.

PubMed

Browndyke, Jeffrey N; Berger, Miles; Smith, Patrick J; Harshbarger, Todd B; Monge, Zachary A; Panchal, Viral; Bisanar, Tiffany L; Glower, Donald D; Alexander, John H; Cabeza, Roberto; Welsh-Bohmer, Kathleen; Newman, Mark F; Mathew, Joseph P

2018-02-01

Older adults often display postoperative cognitive decline (POCD) after surgery, yet it is unclear to what extent functional connectivity (FC) alterations may underlie these deficits. We examined for postoperative voxel-wise FC changes in response to increased working memory load demands in cardiac surgery patients and nonsurgical controls. Older cardiac surgery patients (n = 25) completed a verbal N-back working memory task during MRI scanning and cognitive testing before and 6 weeks after surgery; nonsurgical controls with cardiac disease (n = 26) underwent these assessments at identical time intervals. We measured postoperative changes in degree centrality, the number of edges attached to a brain node, and local coherence, the temporal homogeneity of regional functional correlations, using voxel-wise graph theory-based FC metrics. Group × time differences were evaluated in these FC metrics associated with increased N-back working memory load (2-back > 1-back), using a two-stage partitioned variance, mixed ANCOVA. Cardiac surgery patients demonstrated postoperative working memory load-related degree centrality increases in the left dorsal posterior cingulate cortex (dPCC; p < .001, cluster p-FWE < .05). The dPCC also showed a postoperative increase in working memory load-associated local coherence (p < .001, cluster p-FWE < .05). dPCC degree centrality and local coherence increases were inversely associated with global cognitive change in surgery patients (p < .01), but not in controls. Cardiac surgery patients showed postoperative increases in working memory load-associated degree centrality and local coherence of the dPCC that were inversely associated with postoperative global cognitive outcomes and independent of perioperative cerebrovascular damage. © 2017 Wiley Periodicals, Inc.

Cardiac changes induced by immersion and breath-hold diving in humans.

PubMed

Marabotti, Claudio; Scalzini, Alessandro; Cialoni, Danilo; Passera, Mirko; L'Abbate, Antonio; Bedini, Remo

2009-01-01

To evaluate the separate cardiovascular response to body immersion and increased environmental pressure during diving, 12 healthy male subjects (mean age 35.2 +/- 6.5 yr) underwent two-dimensional Doppler echocardiography in five different conditions: out of water (basal); head-out immersion while breathing (condition A); fully immersed at the surface while breathing (condition B) and breath holding (condition C); and breath-hold diving at 5-m depth (condition D). Heart rate, left ventricular volumes, stroke volume, and cardiac output were obtained by underwater echocardiography. Early (E) and late (A) transmitral flow velocities, their ratio (E/A), and deceleration time of E (DTE) were also obtained from pulsed-wave Doppler, as left ventricular diastolic function indexes. The experimental protocol induced significant reductions in left ventricular volumes, left ventricular stroke volume (P < 0.05), cardiac output (P < 0.001), and heart rate (P < 0.05). A significant increase in E peak (P < 0.01) and E/A (P < 0.01) and a significant reduction of DTE (P < 0.01) were also observed. Changes occurring during diving (condition D) accounted for most of the changes observed in the experimental series. In particular, cardiac output at condition D was significantly lower compared with each of the other experimental conditions, E/A was significantly higher during condition D than in conditions A and C. Finally, DTE was significantly shorter at condition D than in basal and condition C. This study confirms a reduction of cardiac output in diving humans. Since most of the changes were observed during diving, the increased environmental pressure seems responsible for this hemodynamic rearrangement. Left ventricular diastolic function changes suggest a constrictive effect on the heart, possibly accounting for cardiac output reduction.

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.

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.

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.

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.

Age-Related Differences of Maximum Phonation Time in Patients after Cardiac Surgery

PubMed Central

Kasahara, Yusuke; Hiraki, Koji; Hirano, Yasuyuki; Watanabe, Satoshi

2017-01-01

Background and aims: Maximum phonation time (MPT), which is related to respiratory function, is widely used to evaluate maximum vocal capabilities, because its use is non-invasive, quick, and inexpensive. We aimed to examine differences in MPT by age, following recovery phase II cardiac rehabilitation (CR). Methods: This longitudinal observational study assessed 50 consecutive cardiac patients who were divided into the middle-aged group (<65 years, n = 29) and older-aged group (≥65 years, n = 21). MPTs were measured at 1 and 3 months after cardiac surgery, and were compared. Results: The duration of MPT increased more significantly from month 1 to month 3 in the middle-aged group (19.2 ± 7.8 to 27.1 ± 11.6 s, p < 0.001) than in the older-aged group (12.6 ± 3.5 to 17.9 ± 6.0 s, p < 0.001). However, no statistically significant difference occurred in the % change of MPT from 1 month to 3 months after cardiac surgery between the middle-aged group and older-aged group, respectively (41.1% vs. 42.1%). In addition, there were no significant interactions of MPT in the two groups for 1 versus 3 months (F = 1.65, p = 0.20). Conclusion: Following phase II, CR improved MPT for all cardiac surgery patients. PMID:29267218

Age-Related Differences of Maximum Phonation Time in Patients after Cardiac Surgery.

PubMed

Izawa, Kazuhiro P; Kasahara, Yusuke; Hiraki, Koji; Hirano, Yasuyuki; Watanabe, Satoshi

2017-12-21

Background and aims: Maximum phonation time (MPT), which is related to respiratory function, is widely used to evaluate maximum vocal capabilities, because its use is non-invasive, quick, and inexpensive. We aimed to examine differences in MPT by age, following recovery phase II cardiac rehabilitation (CR). Methods: This longitudinal observational study assessed 50 consecutive cardiac patients who were divided into the middle-aged group (<65 years, n = 29) and older-aged group (≥65 years, n = 21). MPTs were measured at 1 and 3 months after cardiac surgery, and were compared. Results: The duration of MPT increased more significantly from month 1 to month 3 in the middle-aged group (19.2 ± 7.8 to 27.1 ± 11.6 s, p < 0.001) than in the older-aged group (12.6 ± 3.5 to 17.9 ± 6.0 s, p < 0.001). However, no statistically significant difference occurred in the % change of MPT from 1 month to 3 months after cardiac surgery between the middle-aged group and older-aged group, respectively (41.1% vs. 42.1%). In addition, there were no significant interactions of MPT in the two groups for 1 versus 3 months (F = 1.65, p = 0.20). Conclusion: Following phase II, CR improved MPT for all cardiac surgery patients.

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.

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.

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 and renal function in a large cohort of amateur marathon runners.

PubMed

Hewing, Bernd; Schattke, Sebastian; Spethmann, Sebastian; Sanad, Wasiem; Schroeckh, Sabrina; Schimke, Ingolf; Halleck, Fabian; Peters, Harm; Brechtel, Lars; Lock, Jürgen; Baumann, Gert; Dreger, Henryk; Borges, Adrian C; Knebel, Fabian

2015-03-21

Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

Evaluation of right ventricular Tei index (index of myocardial performance) in healthy dogs and dogs with tricuspid regurgitation.

PubMed

Teshima, Kenji; Asano, Kazushi; Iwanaga, Koji; Koie, Hiroshi; Uechi, Masami; Kato, Yuka; Kutara, Kenji; Edamura, Kazuya; Hasegawa, Atsuhiko; Tanaka, Shigeo

2006-12-01

Right ventricular (RV) Tei index (index of myocardial performance) has been demonstrated to be clinically useful in estimating RV function in various human cardiac diseases. The purposes of this study were to validate the correlation between RV Tei index and RV function obtained by cardiac catheterization in healthy dogs, and to evaluate the RV Tei index in dogs with tricuspid regurgitation (TR). In healthy dogs, the RV Tei index significantly correlated with the RV peak +dP/dt (r=-0.80, p<0.0001) and -dP/dt (r=0.69, p=0.0001). In normal dogs, the RV Tei index was not significantly correlated with heart rate, body weight, and age. The RV Tei index significantly increased in dogs with moderate to severe TR (0.39 +/- 0.35, p=0.0015), filariasis (0.46 +/- 0.16, p=0.0131), and trivial to mild TR and severe mitral regurgitation (MR; 0.61 +/- 0.14, p=0.0017) when compared with the normal dogs (0.17 +/- 0.10). In addition, the RV Tei index in dogs with TR significantly increased in association with pulmonary hypertension [PH(-), 0.19 +/- 0.09; PH(+), 0.65 +/- 0.14; respectively p<0.0001]. Our study has demonstrated that RV Tei index is a feasible approach to estimate RV function in dogs and is not influenced by heart rate, body weight, and aging. Further investigations are required to clarify the clinical significance of RV Tei index in dogs with right-sided cardiac diseases.

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

Influence of Smoking Consumption and Nicotine Dependence Degree in Cardiac Autonomic Modulation

PubMed Central

dos Santos, Ana Paula Soares; Ramos, Dionei; de Oliveira, Gabriela Martins; dos Santos, Ana Alice Soares; Freire, Ana Paula Coelho Figueira; It, Juliana Tiyaki; Fernandes, Renato Peretti Prieto; Vanderlei, Luiz Carlos Marques; Ramos, Ercy Mara Cipulo

2016-01-01

Background Smoking consumption alters cardiac autonomic function. Objective Assess the influence of the intensity of smoking and the nicotine dependence degree in cardiac autonomic modulation evaluated through index of heart rate variability (HRV). Methods 83 smokers, of both genders, between 50 and 70 years of age and with normal lung function were divided according to the intensity of smoking consumption (moderate and severe) and the nicotine dependency degree (mild, moderate and severe). The indexes of HRV were analyzed in rest condition, in linear methods in the time domain (TD), the frequency domain (FD) and through the Poincaré plot. For the comparison of smoking consumption, unpaired t test or Mann-Whitney was employed. For the analysis between the nicotine dependency degrees, we used the One-way ANOVA test, followed by Tukey's post test or Kruskal-Wallis followed by Dunn's test. The significance level was p < 0,05. Results Differences were only found when compared to the different intensities of smoking consumption in the indexes in the FD. LFun (62.89 ± 15.24 vs 75.45 ± 10.28), which corresponds to low frequency spectrum component in normalized units; HFun (37.11 ± 15.24 vs 24.55 ± 10.28), which corresponds to high frequency spectrum component in normalized units and in the LF/HF ratio (2.21 ± 1.47 vs 4.07 ± 2.94). However, in the evaluation of nicotine dependency, significant differences were not observed (p > 0.05). Conclusion Only the intensity of smoking consumption had an influence over the cardiac autonomic modulation of the assessed tobacco smokers. Tobacco smokers with severe intensity of smoking consumption presented a lower autonomic modulation than those with moderate intensity. PMID:27142649

Randomized Clinical Trial of Preoperative Feeding to Evaluate Intestinal Barrier Function in Neonates Requiring Cardiac Surgery.

PubMed

Zyblewski, Sinai C; Nietert, Paul J; Graham, Eric M; Taylor, Sarah N; Atz, Andrew M; Wagner, Carol L

2015-07-01

To evaluate intestinal barrier function in neonates undergoing cardiac surgery using lactulose/mannitol (L/M) ratio measurements, and to determine correlations with early breast milk feeding. This was a single-center, prospective, randomized pilot study of 27 term-born neonates (≥ 37 weeks gestation) requiring cardiac surgery who were randomized to 1 of 2 preoperative feeding groups: nil per os (NPO) or trophic (10 mL/kg/day) breast milk feeds. At 3 time points (preoperative [preop], postoperative [postop] day 7, and postop day 14), subjects were administered an oral L/M solution, after which urine L/M ratios were measured using gas chromatography, with higher ratios indicative of increased intestinal permeability. Trends over time in the mean urine L/M ratios for each group were estimated using a general linear mixed model. There were no adverse events related to preoperative trophic feeding. In the NPO group (n = 13), the mean urine L/M ratio was 0.06 at preop, 0.12 at postop day 7, and 0.17 at postop day 14. In the trophic breast milk feeds group (n = 14), the mean urine L/M ratio was 0.09 at preop, 0.19 at postop day 7, and 0.15 at postop day 14. In both groups, L/M ratios were significantly higher at postop day 7 and postop day 14 compared with preop (P < .05). Neonates have increased intestinal permeability after cardiac surgery extending to at least postop day 14. This pilot study was not powered to detect differences in benefit or adverse events comparing the NPO and trophic breast milk feeds groups. Further studies to identify mechanisms of intestinal injury and therapeutic interventions are warranted. Registered with ClinicalTrials.gov: NCT01475357. Copyright © 2015 Elsevier Inc. All rights reserved.

Akt2 Knockout Alleviates Prolonged Caloric Restriction-Induced Change in Cardiac Contractile Function through Regulation of Autophagy

PubMed Central

Zhang, Yingmei; Han, Xuefeng; Hu, Nan; Huff, Anna F.; Gao, Feng; Ren, Jun

2014-01-01

Caloric restriction leads to changes in heart geometry and function although the underlying mechanism remains elusive. Autophagy, a conserved pathway for degradation of intracellular proteins and organelles, preserves energy and nutrient in the face of caloric insufficiency. This study was designed to examine the role of Akt2 in prolonged caloric restriction-induced change in cardiac homeostasis and the underlying mechanism(s) involved. Wild-type (WT) and Akt2 knockout mice were caloric restricted (by 40%) for 30 weeks. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties, autophagy and its regulatory proteins were evaluated. Caloric restriction compromised echocardiographic indices (decreased left ventricular mass, left ventricular diameters and cardiac output), cardiomyocyte contractile and intracellular Ca2+ properties associated with dampened SERCA2a phosphorylation, upregulated phospholamban and autophagy (Beclin-1, Atg7, LC3BII-to-LC3BI ratio), increased autophagy adaptor protein p62, elevated phosphorylation of AMPK, Akt2 and the Akt downstream signal molecule TSC2, the effects of which with the exception of autophagy protein markers (Beclin-1, Atg7, LC3B) and AMPK were mitigated or significantly alleviated by Akt2 knockout. Lysosomal inhibition using bafilomycin A1 negated Akt2 knockout-induced protective effect on p62. Evaluation of downstream signaling molecules of Akt and AMPK including mTOR and ULK1 revealed that caloric restriction suppressed and promoted phosphorylation of mTOR and ULK1, respectively, without affecting total mTOR and ULK1 expression. Akt2 knockout significantly augmented caloric restriction-induced responses on mTOR and ULK1. Taken together, these data suggest a beneficial role of Akt2 knockout in preservation of cardiac homeostasis against prolonged caloric restriction-induced pathological changes possibly through facilitating autophagy. PMID:24368095

Prognostic value of adrenal gland volume after cardiac arrest: Association of CT-scan evaluation with shock and mortality.

PubMed

Mongardon, Nicolas; Savary, Guillaume; Geri, Guillaume; El Bejjani, Marie-Rose; Silvera, Stéphane; Dumas, Florence; Charpentier, Julien; Pène, Frédéric; Mira, Jean-Paul; Cariou, Alain

2018-05-28

Adrenal gland volume is associated with survival in septic shock. As sepsis and post-cardiac arrest syndrome share many pathophysiological features, we assessed the association between adrenal gland volume measured by computerized tomography (CT)-scan and post-cardiac arrest shock and intensive care unit (ICU) mortality, in a large cohort of out-of-hospital cardiac arrest (OHCA) patients. We also investigated the association between adrenal hormonal function and both adrenal gland volume and outcomes. Prospective analysis of CT-scan performed at hospital admission in patients admitted after OHCA (2007-2012). A pair of blinded radiologist calculated manually adrenal gland volume. In a subgroup of patients, plasma cortisol was measured at admission and 60 min after a cosyntropin test. Factors associated with post-cardiac arrest shock and ICU mortality were identified using multivariate logistic regression. Among 775 patients admitted during this period after OHCA, 138 patients were included: 72 patients (52.2%) developed a post-cardiac arrest shock, and 98 patients (71.1%) died. In univariate analysis, adrenal gland volume was not different between patients with and without post-cardiac arrest shock: 10.6 and 11.3 cm 3 , respectively (p = 0.9) and between patients discharged alive or dead: 10.2 and 11.8 cm 3 , respectively (p = 0.4). Multivariate analysis confirmed that total adrenal gland volume was associated neither with post-cardiac arrest shock nor mortality. Neither baseline cortisol level nor delta between baseline and after cosyntropin test cortisol levels were associated with adrenal volume, post-cardiac arrest shock onset or mortality. After OHCA, adrenal gland volume is not associated with post-cardiac arrest shock onset or ICU mortality. Adrenal gland volume does not predict adrenal gland hormonal response. Copyright © 2018 Elsevier B.V. All rights reserved.

Temperature effects on aerobic scope and cardiac performance of European perch (Perca fluviatilis).

PubMed

Jensen, Denise Lyager; Overgaard, Johannes; Wang, Tobias; Gesser, Hans; Malte, Hans

2017-08-01

Several recent studies have highlighted how impaired cardiac performance at high temperatures and in hypoxia may compromise the capacity for oxygen transport. Thus, at high temperatures impaired cardiac capacity is proposed to reduce oxygen transport to a degree that lowers aerobic scope and compromises thermal tolerance (the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis). To investigate this hypothesis, we measured aerobic and cardiac performance of a eurythermal freshwater teleost, the European perch (Perca fluviatilis). Rates of oxygen consumption were measured during rest and activity at temperatures between 5°C and 27°C, and we evaluated cardiac function by in vivo measurements of heart rate and in vitro studies to determine contractility of myocardial strips. Aerobic scope increased progressively from 5°C to 21°C, after which it levelled off. Heart rate showed a similar response. We found little difference between resting and active heart rate at high temperature suggesting that increased cardiac scope during activity is primarily related to changes in stroke volume. To examine the effects of temperature on cardiac capacity, we measured isometric force development in electrically paced myocardial preparations during different combinations of temperature, pacing frequency, oxygenation and adrenergic stimulation. The force-frequency product increased markedly upon adrenergic stimulation at 21 and 27°C (with higher effects at 21°C) and the cardiac preparations were highly sensitive to hypoxia. These findings suggest that at (critically) high temperatures, cardiac output may diminish due to a decreased effect of adrenergic stimulation and that this effect may be further exacerbated if the heart becomes hypoxic. Hence cardiac limitations may contribute to the inability to increase aerobic scope at high temperatures in the European perch (Perca fluviatilis). Copyright © 2017 Elsevier Ltd. All rights reserved.

Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study.

PubMed

Mavinkurve-Groothuis, Annelies M C; Marcus, Karen A; Pourier, Milanthy; Loonen, Jacqueline; Feuth, Ton; Hoogerbrugge, Peter M; de Korte, Chris L; Kapusta, Livia

2013-06-01

The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. Cardiac function of 60 children with ALL was prospectively studied with measurements of cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and conventional and myocardial 2D strain echocardiography before start (T = 0), after 3 months (T = 1), and after 1 year (T = 2), and were compared with 60 healthy age-matched controls. None of the patients showed clinical signs of cardiac failure or abnormal fractional shortening. Cardiac function decreased significantly during treatment and was significantly decreased compared with normal controls. Cardiac troponin T levels were abnormal in 11% of the patients at T = 1 and were significantly related to increased time to global peak systolic longitudinal strain at T = 2 (P = 0.003). N-terminal-pro-brain natriuretic peptide levels were abnormal in 13% of patients at T = 1 and in 20% at T = 2, absolute values increased throughout treatment in 59%. Predictors for abnormal NT-pro-BNP at T = 2 were abnormal NT-pro-BNP at T = 0 and T = 1, for abnormal myocardial 2D strain parameters at T = 2 cumulative anthracycline dose and z-score of the diastolic left ventricular internal diameter at baseline. Children with newly diagnosed ALL showed decline of systolic and diastolic function during treatment with anthracyclines using cardiac biomarkers and myocardial 2D strain echocardiography. N-terminal-pro-brain natriuretic peptide levels were not related to echocardiographic strain parameters and cTnT was not a predictor for abnormal strain at T = 2.Therefore, the combination of cardiac biomarkers and myocardial 2D strain echocardiography is important in the assessment of cardiac function of children with ALL treated with anthracyclines.

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.

Gualou Xiebai Decoction, a Traditional Chinese Medicine, Prevents Cardiac Reperfusion Injury of Hyperlipidemia Rat via Energy Modulation.

PubMed

Yan, Lu-Lu; Zhang, Wei-Yang; Wei, Xiao-Hong; Yan, Li; Pan, Chun-Shui; Yu, Yang; Fan, Jing-Yu; Liu, Yu-Ying; Zhou, Hua; Han, Jing-Yan; Yao, Xin-Sheng

2018-01-01

Background: Gualou Xiebai Decoction (GLXB) is a classic prescription of Chinese medicine used for the treatment of cardiac problems. The present study was designed to explore the effect and mechanism of GLXB on ischemia/reperfusion (I/R) induced disorders in myocardial structure and function, focusing on the regulation of energy metabolism and the RhoA/ROCK pathway. Methods: After hyperlipidemic rat model was established by oral administration of high fat diet, the rats were treated with GLXB for 6 weeks and subjected to 30 min occlusion of the left anterior descending coronary artery (LADCA) followed by 90 min reperfusion to elicit I/R challenge. Myocardial infarct size was assessed by Evans blue-TTC staining. Myocardial blood flow (MBF) and cardiac function were evaluated. Enzyme-linked immunosorbent assay was performed to examine the content of ATP, ADP, AMP, CK, CK-MB, LDH, cTnT, cTnI, and IL-6. Double staining of F-actin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was conducted to assess myocardial apoptosis. Expressions of ATP synthase subunit δ (ATP 5D), and RhoA and ROCK were determined by Western blotting. Results: Administration with GLXB at high dose for 6 weeks protected heart against I/R-induced MBF decrease, myocardial infarction and apoptosis, ameliorated I/R-caused impairment of cardiac function and myocardial structure, restored the decrease in the ratio of ADP/ATP and AMP/ATP, and the expression of ATP 5D with inhibiting the expression of RhoA and ROCK. Conclusions: Treatment with GLXB effectively protects myocardial structure and function from I/R challenge, possibly via regulating energy metabolism involving inactivation of RhoA/ROCK signaling pathway.

Left ventricular diastolic dysfunction in type 2 diabetes patients: a novel 2D strain analysis based on cardiac magnetic resonance imaging.

PubMed

Chen, Qiang; Gan, Yan; Li, Zhi-Yong

2016-09-01

This study was to develop a strain analysis method to evaluate the left ventricular (LV) functions in type 2 diabetic patients with an asymptomatic LV diastolic dysfunction. Two groups (10 asymptomatic type 2 diabetic subjects and 10 control ones) were considered. All of the subjects had normal ejection fraction values but impaired diastolic functions assessed by the transmitral blood flow velocity. For each subject, based on cardiac MRI, global indexes including LV volume, LV myocardial mass, cardiac index (CI), and transmitral peak velocity, were measured, and regional indexes (i.e., LV deformation, strain and strain rate) were calculated through an image-registration technology. Most of the global indexes did not differentiate between the two groups, except for the CI, LV myocardial mass and transmitral peak velocity. While for the regional indexes, the global LV diastolic dysfunction of the diabetic indicated an increased strain (0.08 ± 0.044 vs. -0.031 ± 0.077, p = 0.001) and a reduced strain rate (1.834 ± 0.909 vs. 3.791 ± 2.394, p = 0.033) compared to the controls, moreover, the local LV diastolic dysfunction reflected by the strain and strain rate varied, and the degree of dysfunction gradually decreased from the basal level to the apical level. The results showed that the strain and strain rates are effective to capture the subtle alterations of the LV functions, and the proposed method can be used to estimate the LV myocardial function based on cardiac MRI.

Enhanced differentiation of human embryonic stem cells into cardiomyocytes by combining hanging drop culture and 5-azacytidine treatment.

PubMed

Yoon, Byung Sun; Yoo, Seung Jun; Lee, Jeoung Eun; You, Seungkwon; Lee, Hoon Taek; Yoon, Hyun Soo

2006-04-01

Cell replacement therapy is a promising approach for the treatment of cardiac diseases. It is, however, challenged by a limited supply of appropriate cells. Therefore, we have investigated whether functional cardiomyocytes can be efficiently generated from human embryonic stem cells (hESCs). In this study, we developed an efficient protocol for the generation of functional cardiomyocytes from hESCs by combining hanging drop culture and 5-azacytidine, a well-known demethylating agent, and then evaluated the expression of cardiac-specific markers. hESCs were cultured both in the medium without or with 0.1, 1, or 10 microM of 5-azacytidine under a hanging drop culture. The expression of several cardiac-specific markers was determined by real-time PCR, RT-PCR, immunofluorescence, and confocal microscopy. To verify the structural and functional properties of hESC-derived cardiomyocytes, we performed electron microscopy and electrophysiological recording. The efficiency of beating cell generation was significantly improved in the hanging drop culture compared with that in suspension culture. Treatment of hESCs with 0.1 microM of 5-azacytidine for 1-3 days significantly increased the number of beating cells and simultaneously enhanced the expression of cardiac-specific markers. Transmission electron microscopy and electrophysiological recording showed that hESC-derived cardiomyocytes acquired structural and functional properties of cardiomyocytes. In conclusion, these results suggest that differentiation of hESCs into cardiomyocytes can be enhanced by the combination of hanging drop culture and 5-azacytidine treatment. Also the methylation status of genes related to cardiomyocyte development may play an important role in the differentiation of hESCs into cardiomyocytes.

2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy

PubMed Central

Cheng, Yuanhua; Hogarth, Kaley A.; O'Sullivan, M. Lynne; Regnier, Michael

2015-01-01

Dilated cardiomyopathy (DCM) is a major type of heart failure resulting from loss of systolic function. Naturally occurring canine DCM is a widely accepted experimental paradigm for studying human DCM. 2-Deoxyadenosine triphosphate (dATP) can be used by myosin and is a superior energy substrate over ATP for cross-bridge formation and increased systolic function. The objective of this study was to evaluate the beneficial effect of dATP on contractile function of cardiac myofibrils from dogs with naturally occurring DCM. We measured actomyosin NTPase activity and contraction/relaxation properties of isolated myofibrils from nonfailing (NF) and DCM canine hearts. NTPase assays indicated replacement of ATP with dATP significantly increased myofilament activity in both NF and DCM samples. dATP significantly improved maximal tension of DCM myofibrils to the NF sample level. dATP also restored Ca2+ sensitivity of tension that was reduced in DCM samples. Similarly, dATP increased the kinetics of contractile activation (kACT), with no impact on the rate of cross-bridge tension redevelopment (kTR). Thus, the activation kinetics (kACT/kTR) that were reduced in DCM samples were restored for dATP to NF sample levels. dATP had little effect on relaxation. The rate of early slow-phase relaxation was slightly reduced with dATP, but its duration was not, nor was the fast-phase relaxation or times to 50 and 90% relaxation. Our findings suggest that myosin utilization of dATP improves cardiac myofibril contractile properties of naturally occurring DCM canine samples, restoring them to NF levels, without compromising relaxation. This suggests elevation of cardiac dATP is a promising approach for the treatment of DCM. PMID:26497964

2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy.

PubMed

Cheng, Yuanhua; Hogarth, Kaley A; O'Sullivan, M Lynne; Regnier, Michael; Pyle, W Glen

2016-01-01

Dilated cardiomyopathy (DCM) is a major type of heart failure resulting from loss of systolic function. Naturally occurring canine DCM is a widely accepted experimental paradigm for studying human DCM. 2-Deoxyadenosine triphosphate (dATP) can be used by myosin and is a superior energy substrate over ATP for cross-bridge formation and increased systolic function. The objective of this study was to evaluate the beneficial effect of dATP on contractile function of cardiac myofibrils from dogs with naturally occurring DCM. We measured actomyosin NTPase activity and contraction/relaxation properties of isolated myofibrils from nonfailing (NF) and DCM canine hearts. NTPase assays indicated replacement of ATP with dATP significantly increased myofilament activity in both NF and DCM samples. dATP significantly improved maximal tension of DCM myofibrils to the NF sample level. dATP also restored Ca(2+) sensitivity of tension that was reduced in DCM samples. Similarly, dATP increased the kinetics of contractile activation (kACT), with no impact on the rate of cross-bridge tension redevelopment (kTR). Thus, the activation kinetics (kACT/kTR) that were reduced in DCM samples were restored for dATP to NF sample levels. dATP had little effect on relaxation. The rate of early slow-phase relaxation was slightly reduced with dATP, but its duration was not, nor was the fast-phase relaxation or times to 50 and 90% relaxation. Our findings suggest that myosin utilization of dATP improves cardiac myofibril contractile properties of naturally occurring DCM canine samples, restoring them to NF levels, without compromising relaxation. This suggests elevation of cardiac dATP is a promising approach for the treatment of DCM. Copyright © 2016 the American Physiological Society.

Real-Time Three-Dimensional Echocardiography: Characterization of Cardiac Anatomy and Function-Current Clinical Applications and Literature Review Update.

PubMed

Velasco, Omar; Beckett, Morgan Q; James, Aaron W; Loehr, Megan N; Lewis, Taylor G; Hassan, Tahmin; Janardhanan, Rajesh

2017-01-01

Our review of real-time three-dimensional echocardiography (RT3DE) discusses the diagnostic utility of RT3DE and provides a comparison with two-dimensional echocardiography (2DE) in clinical cardiology. A Pubmed literature search on RT3DE was performed using the following key words: transthoracic, two-dimensional, three-dimensional, real-time, and left ventricular (LV) function. Articles included perspective clinical studies and meta-analyses in the English language, and focused on the role of RT3DE in human subjects. Application of RT3DE includes analysis of the pericardium, right ventricular (RV) and LV cavities, wall motion, valvular disease, great vessels, congenital anomalies, and traumatic injury, such as myocardial contusion. RT3DE, through a transthoracic echocardiography (TTE), allows for increasingly accurate volume and valve motion assessment, estimated LV ejection fraction, and volume measurements. Chamber motion and LV mass approximation have been more accurately evaluated by RT3DE by improved inclusion of the third dimension and quantification of volumetric movement. Moreover, RT3DE was shown to have no statistical significance when comparing the ejection fractions of RT3DE to cardiac magnetic resonance (CMR). Analysis of RT3DE data sets of the LV endocardial exterior allows for the volume to be directly quantified for specific phases of the cardiac cycle, ranging from end systole to end diastole, eliminating error from wall motion abnormalities and asymmetrical left ventricles. RT3DE through TTE measures cardiac function with superior diagnostic accuracy in predicting LV mass, systolic function, along with LV and RV volume when compared with 2DE with comparable results to CMR.

Left ventricular strain and twisting in heart failure with preserved ejection fraction: an updated review.

PubMed

Tadic, Marijana; Pieske-Kraigher, Elisabeth; Cuspidi, Cesare; Genger, Martin; Morris, Daniel A; Zhang, Kun; Walther, Nina Alexandra; Pieske, Burket

2017-05-01

Despite the high prevalence of the patients with heart failure with preserved ejection fraction (HFpEF), our knowledge about this entity, from diagnostic tools to therapeutic approach, is still not well established. The evaluation of patients with HFpEF is mainly based on echocardiography, as the most widely accepted tool in cardiac imaging. Identification of left ventricular (LV) diastolic dysfunction has long been considered as the only responsible for HFpEF, and its evaluation is still "sine qua non" of HFpEF diagnostics. However, one should be aware of the fact that identifying cardiac dysfunction in HFpEF might be very challenging and often needs more complex evaluation of cardiac structure and function. New echocardiographic modalities such as 2D and 3D speckle tracking imaging could help in the diagnosis of HFpEF and provide further information regarding LV function and mechanics. Early diagnosis, medical management, and adequate monitoring of HFpEF patients are prerequisites of modern medical treatment. New healthcare approaches require individualized patient care, which is why clinicians should have all clinical, laboratory, and diagnostic data before making final decisions about the treatment of any patients. This is particularly important for HFpEF that often remains undiagnosed for quite a long time, which further prolongs the beginning of adequate treatment and brings into question outcome of these patients. The aim of this article is to provide the overview of the main principles of LV mechanics and summarize recent data regarding LV strain in patients with HFpEF.

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.

Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

PubMed

van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

2013-04-01

Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P < .05). Intraoperative administration of a single high-dose of ATG-Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

Detecting Regional Myocardial Abnormalities in Patients With Wolff-Parkinson-White Syndrome With the Use of ECG-Gated Cardiac MDCT.

PubMed

Lee, Hye-Jeong; Uhm, Jae-Sun; Joung, Boyoung; Hong, Yoo Jin; Hur, Jin; Choi, Byoung Wook; Kim, Young Jin

2016-04-01

Myocardial dyskinesia caused by the accessory pathway and related reversible heart failure have been well documented in echocardiographic studies of pediatric patients with Wolff-Parkinson-White (WPW) syndrome. However, the long-term effects of dyskinesia on the myocardium of adult patients have not been studied in depth. The goal of the present study was to evaluate regional myocardial abnormalities on cardiac CT examinations of adult patients with WPW syndrome. Of 74 patients with WPW syndrome who underwent cardiac CT from January 2006 through December 2013, 58 patients (mean [± SD] age, 52.2 ± 12.7 years), 36 (62.1%) of whom were men, were included in the study after the presence of combined cardiac disease was excluded. Two observers blindly evaluated myocardial thickness and attenuation on cardiac CT scans. On the basis of CT findings, patients were classified as having either normal or abnormal findings. We compared the two groups for other clinical findings, including observations from ECG, echocardiography, and electrophysiologic study. Of the 58 patients studied, 16 patients (27.6%) were found to have myocardial abnormalities (i.e., abnormal wall thinning with or without low attenuation). All abnormal findings corresponded with the location of the accessory pathway. Patients with abnormal findings had statistically significantly decreased left ventricular function, compared with patients with normal findings (p < 0.001). The frequency of regional wall motion abnormality was statistically significantly higher in patients with abnormal findings (p = 0.043). However, echocardiography documented structurally normal hearts in all patients. A relatively high frequency (27.6%) of regional myocardial abnormalities was observed on the cardiac CT examinations of adult patients with WPW syndrome. These abnormal findings might reflect the long-term effects of dyskinesia, suggesting irreversible myocardial injury that ultimately causes left ventricular dysfunction.

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.

Cardiac autonomic function in children with type 1 diabetes.

PubMed

Metwalley, Kotb Abbass; Hamed, Sherifa Ahmed; Farghaly, Hekma Saad

2018-06-01

Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). This study aimed to evaluate cardiac autonomic nervous system (ANS) function in children with T1D and its relation to different demographic, clinical and laboratory variable. This cross-sectional study included 60 children with T1D (mean age = 15.1 ± 3.3 years; duration of diabetes = 7.95 ± 3.83 years). The following 8 non-invasive autonomic testing were used for evaluation: heart rate at rest and in response to active standing (30:15 ratio), deep breathing and Valsalva maneuver (indicating parasympathetic function); blood pressure response to standing (orthostatic hypotension or OH), sustained handgrip and cold; and heart rate response to standing or positional orthostatic tachycardia syndrome or POTs (indicating sympathetic function). None had clinically manifest CAN. Compared to healthy children (5%), 36.67% of children with T1D had ≥ 2 abnormal tests (i.e., CAN) (P = 0.0001) which included significantly abnormal heart rate response to standing (POTs) (P = 0.052), active standing (30:15 ratio) (P = 0.0001) and Valsalva maneuver (P = 0.0001), indicating parasympathetic autonomic dysfunction, and blood pressure response to cold (P = 0.01), indicating sympathetic autonomic dysfunction. 54.55, 27.27 and 18.18% had early, definite and severe dysfunction of ANS. All patients had sensorimotor peripheral neuropathy. The longer duration of diabetes (> 5 years), presence of diabetic complications and worse glycemic control were significantly associated with CAN. The study concluded that both parasympathetic and sympathetic autonomic dysfunctions are common in children with T1D particularly with longer duration of diabetes and presence of microvascular complications. What is Known: • Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). • Limited studies evaluated CAN in children with T1D. What is New: • CAN is common in children with T1D. • Cardiac autonomic functions should be assessed in children with T1D particularly in presence of microvascular complications.

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.

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

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.

Eat, breathe, ROS: controlling stem cell fate through metabolism.

PubMed

Kubli, Dieter A; Sussman, Mark A

2017-05-01

Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered: Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary: The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes.

Eat, breathe, ROS: controlling stem cell fate through metabolism

PubMed Central

Kubli, Dieter A.; Sussman, Mark A.

2017-01-01

Introduction Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes. PMID:28406333

Effect of Exercise Training and L-arginine on Oxidative Stress and Left Ventricular Function in the Post-ischemic Failing Rat Heart.

PubMed

Ranjbar, Kamal; Nazem, Farzad; Nazari, Afshin

2016-04-01

The aim of the present study was to evaluate the effect of exercise training (ET) and L-arginine on oxidative stress and ventricular function in rat with myocardial infarction (MI). Four weeks after the surgical procedures, 40 Wistar male rats were randomized to the following groups: MI-sedentary (Sed); MI-exercise (Ex); MI-sedentary + L-arginine (Sed + LA); and MI-exercise + L-arginine (Ex + LA); the rats were subjected to aerobic training in the form of treadmill running. Rats in the L-arginine-treated groups drank water containing 4 % L-arginine. Before and after the training program, all subjects underwent resting echocardiography. Catalase (CAT) glutathione peroxidase (GPx), malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Cardiac output, stroke volume and fractional shortening in Ex and Ex + LA groups significantly increased in comparison with the Sed group. Cardiac systolic function indices in Ex + LA group were significantly greater than Ex group. Also, GPx activity and MDA, respectively, increased and decreased in response to ET, but no change was observed in MPO and CAT. These results suggest that ET increased LV function by decreasing oxidative stress and increasing antioxidant defense system in rats with MI. In addition in response to training, L-arginine appears to have additive effect on cardiac function, but have no effect on oxidative stress indices.

Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

PubMed

Politei, J; Schenone, A B; Cabrera, G; Heguilen, R; Szlago, M

2016-01-01

We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.