The Dark Side of the Moon: The Right Ventricle

PubMed Central

Foschi, Massimiliano; Di Mauro, Michele; Tancredi, Fabrizio; Capparuccia, Carlo; Petroni, Renata; Leonzio, Luigi; Romano, Silvio; Gallina, Sabina; Penco, Maria; Cibelli, Mario; Calafiore, Antonio

2017-01-01

The aim of this review article is to summarize current knowledge of the pathophysiology underlying right ventricular failure (RVF), focusing, in particular, on right ventricular assessment and prognosis. The right ventricle (RV) can tolerate volume overload well, but is not able to sustain pressure overload. Right ventricular hypertrophy (RVH), as a response to increased afterload, can be adaptive or maladaptive. The easiest and most common way to assess the RV is by two-dimensional (2D) trans-thoracic echocardiography measuring surrogate indexes, such as tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and tissue Doppler velocity of the lateral aspect of the tricuspid valvular plane. However, both volumes and function are better estimated by 3D echocardiography and cardiac magnetic resonance (CMR). The prognostic role of the RV in heart failure (HF), pulmonary hypertension (PH), acute myocardial infarction (AMI), and cardiac surgery has been overlooked for many years. However, several recent studies have placed much greater importance on the RV in prognostic assessments. In conclusion, RV dimensions and function should be routinely assessed in cardiovascular disease, as RVF has a significant impact on disease prognosis. In the presence of RVF, different therapeutic approaches, either pharmacological or surgical, may be beneficial. PMID:29367547

Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.

PubMed

Harjola, Veli-Pekka; Mebazaa, Alexandre; Čelutkienė, Jelena; Bettex, Dominique; Bueno, Hector; Chioncel, Ovidiu; Crespo-Leiro, Maria G; Falk, Volkmar; Filippatos, Gerasimos; Gibbs, Simon; Leite-Moreira, Adelino; Lassus, Johan; Masip, Josep; Mueller, Christian; Mullens, Wilfried; Naeije, Robert; Nordegraaf, Anton Vonk; Parissis, John; Riley, Jillian P; Ristic, Arsen; Rosano, Giuseppe; Rudiger, Alain; Ruschitzka, Frank; Seferovic, Petar; Sztrymf, Benjamin; Vieillard-Baron, Antoine; Yilmaz, Mehmet Birhan; Konstantinides, Stavros

2016-03-01

Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches. © 2016 The Authors European Journal of Heart Failure © 2016 European Society of Cardiology.

Role of myocardial hypertrophy on acute and chronic right ventricular performance in relation to chronic volume overload in a porcine model: relevance for the surgical management of tetralogy of Fallot.

PubMed

Bove, Thierry; Vandekerckhove, Kristof; Bouchez, Stefaan; Wouters, Patrick; Somers, Pamela; Van Nooten, Guido

2014-06-01

The age for correction of tetralogy of Fallot has progressively declined to the postnatal period, often despite an increased rate of transannular patch repair. However, the long-term effect of premature exposure to chronic pulmonary insufficiency on the right ventricle remains unknown. On the basis of the relationship between the duration of pressure overload and age, the role of previous pressure load-related hypertrophy on right ventricular (RV) performance after chronic volume overload was investigated in a porcine model. RV hypertrophy (RVH), induced by pulmonary artery banding, was studied in pigs with (RVH plus pulmonary insufficiency [PI]) and without (RVH) subsequent PI. The effect of volume overload was compared between these 2 groups and pigs without RVH but with PI and controls (sham). Both acute and chronic effects on RV function were studied using conductance technology and validated using echocardiography. After chronic volume overload, the end-systolic and end-diastolic volumes were smaller in the RVH+PI group than in the PI group, including a lower pulmonary regurgitation fraction (25% ± 5% vs 35% ± 5%; P = .002). RVH resulted in better preserved systolic function, confirmed by an increased preload recruitable stroke work slope (14.7 ± 1.8 vs 9.3 ± 1.3 Mw.s/mL; P = .025) and higher RV ejection fraction (51% ± 3% vs 45% ± 4%; P = .05). Myocardial stiffness was impaired in the RVH+PI group versus the PI group (β, 0.19 ± 0.03 vs 0.12 ± 0.02 mL(-1); P = .001), presenting restrictive physiology only in the condition associating RVH and PI. The results of the present study have demonstrated that RVH attenuates the RV remodeling process related to chronic PI. It enables better preservation of contractility but at the cost of sustained diastolic impairment. These findings might help to determine the timing and strategy for repair of tetralogy of Fallot when RV outflow tract morphology indicates a definite need for transannular reconstruction. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in an animal model with right ventricular failure after pulmonary artery banding.

PubMed

Hyldebrandt, Janus Adler; Sivén, Eleonora; Agger, Peter; Frederiksen, Christian Alcaraz; Heiberg, Johan; Wemmelund, Kristian Borup; Ravn, Hanne Berg

2015-07-01

Right ventricular (RV) failure due to chronic pressure overload is a main determinant of outcome in congenital heart disease. Medical management is challenging because not only contractility but also the interventricular relationship is important for increasing cardiac output. This study evaluated the effect of milrinone alone and in combination with epinephrine or dopamine on hemodynamics, ventricular performance, and the interventricular relationship. RV failure was induced in 21 Danish landrace pigs by pulmonary artery banding. After 10 wk, animals were reexamined using biventricular pressure-volume conductance catheters. The maximum pressure in the RV increased by 113% (P < 0.0001) and end-diastolic volume by 43% (P < 0.002), while left ventricular (LV) pressure simultaneously decreased (P = 0.006). Concomitantly, mean arterial pressure (MAP; -16%, P = 0.01), cardiac index (CI; -23%, P < 0.0001), and mixed venous oxygen saturation (SvO2 ; -40%, P < 0.0001) decreased. Milrinone increased CI (11%, P = 0.008) and heart rate (HR; 21%, P < 0.0001). Stroke volume index (SVI) decreased (7%, P = 0.03), although RV contractility was improved. The addition of either epinephrine or dopamine further increased CI and HR in a dose-dependent manner but without any significant differences between the two interventions. A more pronounced increase in biventricular contractility was observed in the dopamine-treated animals. LV volume was reduced in both the dopamine and epinephrine groups with increasing doses In the failing pressure overloaded RV, milrinone improved CI and increased contractility. Albeit additional dose-dependent effects of both epinephrine and dopamine on CI and contractility, neither of the interventions improved SVI due to reduced filling of the LV. Copyright © 2015 the American Physiological Society.

A rabbit model of progressive chronic right ventricular pressure overload.

PubMed

Roldan Ramos, Sara; Pieles, Guido; Hui, Wei; Slorach, Cameron; Redington, Andrew N; Friedberg, Mark K

2018-04-01

Right ventricular (RV) failure from increased pressure loading is a frequent consequence of acquired and congenital heart diseases. However, the mechanisms involved in their pathophysiology are still unclear, and few data exist on RV pressure-loading models and early versus late effects on RV and left ventricular responses. We characterized a rabbit model of chronic RV pressure overload and early-late effects on biventricular function. Twenty-one New Zealand white rabbits were randomized into 3 groups: (i) sham, (ii) pulmonary artery (PA) banding (PAB) for 3 weeks (PAB3W) and (iii) PAB for 6 weeks (PAB6W). Progressive RV pressure overload was created by serial band inflation using an adjustable device. Molecular, echocardiographic and haemodynamic studies were performed. RV pressure overload was achieved with clinical manifestations of RV failure. Heart and liver weights were significantly higher after PAB. PAB-induced echocardiographic ventricular remodelling increased wall thickness and stress and ventricular dilation. Cardiac output (ml/min) (sham 172.4 ± 42.86 vs PAB3W 103.1 ± 23.14 vs PAB6W 144 ± 60.9, P = 0.0027) and systolic and diastolic functions decreased; with increased RV end-systolic and end-diastolic pressures (mmHg) (sham 1.6 ± 0.66 vs PAB3W 3.9 ± 1.8 vs PAB6W 5.2 ± 2.2, P = 0.0103), despite increased contractility [end-systolic pressure-volume relationship (mmHg/ml), sham 3.76 ± 1.76 vs PAB3W 12.21 ± 3.44 vs PAB6W 19.4 ± 6.88, P < 0.0001]. Functional parameters further worsened after PAB6W versus PAB3W. LV contractility increased in both the PAB groups, despite worsening of other invasive measures of systolic and diastolic functions. We describe a novel, unique model of chronic RV pressure overload leading to early biventricular dysfunction and fibrosis with further progression at 6 weeks. These findings can aid in guiding management.

Right ventricular volumes and function in thalassemia major patients in the absence of myocardial iron overload

PubMed Central

2010-01-01

Aim We aimed to define reference ranges for right ventricular (RV) volumes, ejection fraction (EF) in thalassemia major patients (TM) without myocardial iron overload. Methods and results RV volumes, EF and mass were measured in 80 TM patients who had no myocardial iron overload (myocardial T2* > 20 ms by cardiovascular magnetic resonance). All patients were receiving deferoxamine chelation and none had evidence of pulmonary hypertension or other cardiovascular comorbidity. Forty age and sex matched healthy non-anemic volunteers acted as controls. The mean RV EF was higher in TM patients than controls (males 66.2 ± 4.1% vs 61.6 ± 6%, p = 0.0009; females 66.3 ± 5.1% vs 62.6 ± 6.4%, p = 0.017), which yielded a raised lower threshold of normality for RV EF in TM patients (males 58.0% vs 50.0% and females 56.4% vs 50.1%). RV end-diastolic volume index was higher in male TM patients (mean 98.1 ± 17.3 mL vs 88.4 ± 11.2 mL/m2, p = 0.027), with a higher upper limit (132 vs 110 mL/m2) but this difference was of borderline significance for females (mean 86.5 ± 13.6 mL vs 80.3 ± 12.8 mL/m2, p = 0.09, with upper limit of 113 vs 105 mL/m2). The cardiac index was raised in TM patients (males 4.8 ± 1.0 L/min vs 3.4 ± 0.7 L/min, p < 0.0001; females 4.5 ± 0.8 L/min vs 3.2 ± 0.8 L/min, p < 0.0001). No differences in RV mass index were identified. Conclusion The normal ranges for functional RV parameters in TM patients with no evidence of myocardial iron overload differ from healthy non-anemic controls. The new reference RV ranges are important for determining the functional effects of myocardial iron overload in TM patients. PMID:20416084

Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

PubMed

Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

2016-12-01

Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fibroblasts and the extracellular matrix in right ventricular disease.

PubMed

Frangogiannis, Nikolaos G

2017-10-01

Right ventricular failure predicts adverse outcome in patients with pulmonary hypertension (PH), and in subjects with left ventricular heart failure and is associated with interstitial fibrosis. This review manuscript discusses the cellular effectors and molecular mechanisms implicated in right ventricular fibrosis. The right ventricular interstitium contains vascular cells, fibroblasts, and immune cells, enmeshed in a collagen-based matrix. Right ventricular pressure overload in PH is associated with the expansion of the fibroblast population, myofibroblast activation, and secretion of extracellular matrix proteins. Mechanosensitive transduction of adrenergic signalling and stimulation of the renin-angiotensin-aldosterone cascade trigger the activation of right ventricular fibroblasts. Inflammatory cytokines and chemokines may contribute to expansion and activation of macrophages that may serve as a source of fibrogenic growth factors, such as transforming growth factor (TGF)-β. Endothelin-1, TGF-βs, and matricellular proteins co-operate to activate cardiac myofibroblasts, and promote synthesis of matrix proteins. In comparison with the left ventricle, the RV tolerates well volume overload and ischemia; whether the right ventricular interstitial cells and matrix are implicated in these favourable responses remains unknown. Expansion of fibroblasts and extracellular matrix protein deposition are prominent features of arrhythmogenic right ventricular cardiomyopathies and may be implicated in the pathogenesis of arrhythmic events. Prevailing conceptual paradigms on right ventricular remodelling are based on extrapolation of findings in models of left ventricular injury. Considering the unique embryologic, morphological, and physiologic properties of the RV and the clinical significance of right ventricular failure, there is a need further to dissect RV-specific mechanisms of fibrosis and interstitial remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system.

PubMed

Adamson, Philip B; Magalski, Anthony; Braunschweig, Frieder; Böhm, Michael; Reynolds, Dwight; Steinhaus, David; Luby, Allyson; Linde, Cecilia; Ryden, Lars; Cremers, Bodo; Takle, Teri; Bennett, Tom

2003-02-19

This study examined the characteristics of continuously measured right ventricular (RV) hemodynamic information derived from an implantable hemodynamic monitor (IHM) in heart failure patients. Hemodynamic monitoring might improve the day-to-day management of patients with chronic heart failure (CHF). Little is known about the characteristics of long-term hemodynamic information in patients with CHF or how such information relates to meaningful clinical events. Thirty-two patients with CHF received a permanent RV IHM system similar to a single-lead pacemaker. Right ventricular systolic and diastolic pressures, heart rate, and pressure derivatives were continuously measured for nine months without using the data for clinical decision-making or management of patients. Data were then made available to clinical providers, and the patients were followed up for 17 months. Pressure characteristics during optimal volume, clinically determined volume-overload exacerbations, and volume depletion events were examined. The effect of IHM on hospitalizations was examined using the patients' historical controls. Long-term RV pressure measurements had either marked variability or minimal time-related changes. During 36 volume-overload events, RV systolic pressures increased by 25 +/- 4% (p < 0.05) and heart rate increased by 11 +/- 2% (p < 0.05). Pressure increases occurred in 9 of 12 events 4 +/- 2 days before the exacerbations requiring hospitalization. Hospitalizations before using IHM data for clinical management averaged 1.08 per patient year and decreased to 0.47 per patient-year (57% reduction, p < 0.01) after hemodynamic data were used. Long-term ambulatory pressure measurements from an IHM may be helpful in guiding day-to-day clinical management, with a potentially favorable impact on CHF hospitalizations.

Continuous-flow cardiac assistance: effects on aortic valve function in a mock loop.

PubMed

Tuzun, Egemen; Rutten, Marcel; Dat, Marco; van de Vosse, Frans; Kadipasaoglu, Cihan; de Mol, Bas

2011-12-01

As the use of left ventricular assist devices (LVADs) to treat end-stage heart failure has become more widespread, leaflet fusion--with resul-tant aortic regurgitation--has been observed more frequently. To quantitatively assess the effects of nonpulsatile flow on aortic valve function, we tested a continuous-flow LVAD in a mock circulatory system (MCS) with an interposed valve. To mimic the hemodynamic characteristics of LVAD patients, we utilized an MCS in which a Jarvik 2000 LVAD was positioned at the base of a servomotor-operated piston pump (left ventricular chamber). We operated the LVAD at 8000 to 12,000 rpm, changing the speed in 1000-rpm increments. At each speed, we first varied the outflow resistance at a constant stroke volume, then varied the stroke volume at a constant outflow resistance. We measured the left ventricular pressure, aortic pressure, pump flow, and total flow, and used these values to compute the change, if any, in the aortic duty cycle (aortic valve open time) and transvalvular aortic pressure loads. Validation of the MCS was demonstrated by the simulation of physiologic pressure and flow waveforms. At increasing LVAD speeds, the mean aortic pressure load steadily increased, while the aortic duty cycle steadily decreased. Changes were consistent for each MCS experimental setting, despite variations in stroke volume and outflow resistance. Increased LVAD flow results in an impaired aortic valve-open time due to a pressure overload above the aortic valve. Such an overload may initiate structural changes, causing aortic leaflet fusion and/or regurgitation. Copyright © 2011 Elsevier Inc. All rights reserved.

Ductal stenting retrains the left ventricle in transposition of great arteries with intact ventricular septum.

PubMed

Sivakumar, Kothandam; Francis, Edwin; Krishnan, Prasad; Shahani, Jagdish

2006-11-01

In late presenters with transposition of the great arteries, intact ventricular septum, and regressing left ventricle, left ventricular retraining by pulmonary artery banding and aortopulmonary shunt is characterized by a stormy postoperative course and high costs. Ductal stenting in the cardiac catheterization laboratory is conceptualized to retrain the left ventricle with less morbidity. Recanalization and transcatheter stenting of patent ductus arteriosus was performed in patients with transposition to induce pressure and volume overload to the regressing left ventricle. Serial echocardiographic monitoring of left ventricular shape, mass, free wall thickness, and volumes was done, and once the left ventricle was adequately prepared, an arterial switch was performed. The ductal stent was removed and the remaining surgical steps were similar to a 1-stage arterial switch operation. Postoperative course, need for inotropic agents, and left ventricular function were monitored. Ductal stenting in 2 patients aged 3 months resulted in improvement of indexed left ventricular mass from 18.9 to 108.5 g/m2, left ventricular free wall thickness from 2.5 to 4.8 mm, and indexed left ventricular volumes from 7.6 to 29.5 mL/m2 within 3 weeks. Both patients underwent arterial switch (bypass times 125 and 158 minutes) uneventfully, needed inotropic agents and ventilatory support for 3 days, and were discharged in 8 and 10 days. Ductal stenting is a less morbid method of left ventricular retraining in transposition of the great arteries with regressed left ventricle. Its major advantages lie in avoiding pulmonary artery distortion and neoaortic valve regurgitation resulting from banding and also in avoiding thoracotomy.

Intensive Hemodialysis, Left Ventricular Hypertrophy, and Cardiovascular Disease.

PubMed

McCullough, Peter A; Chan, Christopher T; Weinhandl, Eric D; Burkart, John M; Bakris, George L

2016-11-01

The prevalence of cardiovascular disease, including cardiac arrhythmia, coronary artery disease, cardiomyopathy, and valvular heart disease, is higher in hemodialysis (HD) patients than in the US resident population. Cardiovascular disease is the leading cause of death in HD patients and the principal discharge diagnosis accompanying 1 in 4 hospital admissions. Furthermore, the rate of hospital admissions for either heart failure or fluid overload is persistently high despite widespread use of β-blockers and renin-angiotensin system inhibitors and attempts to manage fluid overload with ultrafiltration. An important predictor of cardiovascular mortality and morbidity in dialysis patients is left ventricular hypertrophy (LVH). LVH is an adaptive response to increased cardiac work, typically caused by combined pressure and volume overload, resulting in cardiomyocyte hypertrophy and increased intercellular matrix. In new dialysis patients, the prevalence of LVH is 75%. Regression of LVH may reduce cardiovascular risk, including the incidence of heart failure, complications after myocardial infarction, and sudden arrhythmic death. Multiple randomized clinical trials show that intensive HD reduces left ventricular mass, a measure of LVH. Short daily and nocturnal schedules in the Frequent Hemodialysis Network trial reduced left ventricular mass by 14 (10%) and 11 (8%) g, respectively, relative to 3 sessions per week. Comparable efficacy was observed in an earlier trial of nocturnal HD. Intensive HD also improves cardiac rhythm. Clinical benefits have been reported only in observational studies. Daily home HD is associated with 17% and 16% lower risks for cardiovascular death and hospitalization, respectively; admissions for cerebrovascular disease, heart failure, and hypertensive disease, which collectively constitute around half of cardiovascular hospitalizations, were less likely with daily home HD. Relative to peritoneal dialysis, daily home HD is likewise associated with lower risk for cardiovascular hospitalization. In conclusion, intensive HD likely reduces left ventricular mass and may lead to lower risks for adverse cardiac events. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Intrathoracic impedance monitor alarm in a patient with cardiac resynchronisation therapy and advanced lung carcinoma.

PubMed

Cvijić, Marta; Zižek, David; Antolič, Bor; Zupan, Igor

2013-01-01

The intrathoracic impedance monitor system measures impedance between the device case and the right ventricular coil and reflects intrathoracic fluid status. It is used to detect early volume overload in patients with chronic heart failure. We report a case of inappropriate activation of the intrathoracic impedance monitor alarm in a patient with epidermoid lung cancer and pleural carcinosis.

Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure.

PubMed

Guichard, Jason L; Rogowski, Michael; Agnetti, Giulio; Fu, Lianwu; Powell, Pamela; Wei, Chih-Chang; Collawn, James; Dell'Italia, Louis J

2017-07-01

Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of αB-crystallin from the Z disk with increased α, β-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO. NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial architecture throughout the progression of volume overload heart failure, suggesting a causal link between desmin cleavage and mitochondrial disorganization and damage.

"Reversibility of Cardiovascular Injury With CPAP Use: Mechanisms Involved"

ClinicalTrials.gov

2015-09-29

Sleep Apnea, Obstructive; Hypoxia; Hypercapnia; Sleep Disorders; Obesity; Hypertension; Coronary Artery Vasospasm; Right Ventricular Overload; Left Ventricular Function Systolic Dysfunction; Ventricular Hypertrophy

TVP1022 attenuates cardiac remodeling and kidney dysfunction in experimental volume overload-induced congestive heart failure.

PubMed

Abassi, Zaid A; Barac, Yaron D; Kostin, Sawa; Roguin, Ariel; Ovcharenko, Elena; Awad, Hoda; Blank, Ayelet; Bar-Am, Orit; Amit, Tamar; Schaper, Jutta; Youdim, Moussa; Binah, Ofer

2011-07-01

Despite the availability of many pharmacological and mechanical therapies, the mortality rate among patients with congestive heart failure (CHF) remains high. We tested the hypothesis that TVP1022 (the S-isomer of rasagiline; Azilect), a neuroprotective and cytoprotective molecule, is also cardioprotective in the settings of experimental CHF in rats. In rats with volume overload-induced CHF, we investigated the therapeutic efficacy of TVP1022 (7.5 mg/kg) on cardiac function, structure, biomarkers, and kidney function. Treatment with TVP1022 for 7 days before CHF induction prevented the increase in left ventricular end-diastolic area and end-systolic area, and the decrease in fractional shortening measured 14 days after CHF induction. Additionally, TVP1022 pretreatment attenuated CHF-induced cardiomyocyte hypertrophy, fibrosis, plasma and ventricular B-type natriuretic peptide levels, and reactive oxygen species expression. Further, in CHF rats, TVP1022 decreased cytochrome c and caspase 3 expression, thereby contributing to the cardioprotective efficacy of the drug. TVP1022 also enhanced the urinary Na(+) excretion and improved the glomerular filtration rate. Similar cardioprotective effects were obtained when TVP1022 was given to rats after CHF induction. TVP1022 attenuated the adverse functional, structural, and molecular alterations in CHF, rendering this drug a promising candidate for improving cardiac and renal function in this disease state.

Metaiodobenzylguanidine (/sup 131/I) scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

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

Rabinovitch, M.A.; Rose, C.P.; Rouleau, J.L.

1987-12-01

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine (/sup 131/I) to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine (/sup 131/I) and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4more » hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine (/sup 131/I) scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine (/sup 123/I) scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.« less

A modified Glenn shunt reduces venous congestion during acute right ventricular failure due to pulmonary banding: a randomized experimental study

PubMed Central

Vikholm, Per; Schiller, Petter; Hellgren, Laila

2014-01-01

OBJECTIVES Right ventricular failure after left ventricular assist device implantation is a serious complication with high rates of mortality and morbidity. It has been demonstrated in experimental settings that volume exclusion of the right ventricle with a modified Glenn shunt can improve haemodynamics during ischaemic right ventricular failure. However, the concept of a modified Glenn shunt is dependent on a normal pulmonary vascular resistance, which can limit its use in some patients. The aim of this study was to explore the effects of volume exclusion with a modified Glenn shunt during right ventricular failure due to pulmonary banding, and to study the alterations in genetic expression in the right ventricle due to pressure and volume overload. METHODS Experimental right ventricular failure was induced in pigs (n = 11) through 2 h of pulmonary banding. The pigs were randomized to either treatment with a modified Glenn shunt and pulmonary banding (n = 6) or solely pulmonary banding (n = 5) as a control group. Haemodynamic measurements, blood samples and right ventricular biopsies for genetic analysis were sampled at baseline, at right ventricular failure (i.e. 2 h of pulmonary banding) and 1 h post-right ventricular failure in both groups. RESULTS Right atrial pressure increased from 10 mmHg (9.0–12) to 18 mmHg (16–22) (P < 0.01) and the right ventricular pressure from 31 mmHg (26–35) to 57 mmHg (49–61) (P < 0.01) after pulmonary banding. Subsequent treatment with the modified Glenn shunt resulted in a decrease in right atrial pressure to 13 mmHg (11–14) (P = 0.03). In the control group, right atrial pressure was unchanged at 19 mmHg (16–20) (P = 0.18). At right heart failure, there was an up-regulation of genes associated with heart failure, inflammation, angiogenesis, negative regulation of cell death and proliferation. CONCLUSIONS Volume exclusion with a modified Glenn shunt during right ventricular failure reduced venous congestion compared with the control group. The state of right heart failure was verified through genetic expressional changes. PMID:24396048

Magnetic Resonance Characterization of Cardiac Adaptation and Myocardial Fibrosis in Pulmonary Hypertension Secondary to Systemic-To-Pulmonary Shunt.

PubMed

Pereda, Daniel; García-Lunar, Inés; Sierra, Federico; Sánchez-Quintana, Damián; Santiago, Evelyn; Ballesteros, Constanza; Encalada, Juan F; Sánchez-González, Javier; Fuster, Valentín; Ibáñez, Borja; García-Álvarez, Ana

2016-09-01

Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR). To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation [n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular end-diastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction. Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation. © 2016 American Heart Association, Inc.

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

PubMed

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

2010-12-01

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

Does load-induced ventricular hypertrophy progress to systolic heart failure?

PubMed

Berenji, Kambeez; Drazner, Mark H; Rothermel, Beverly A; Hill, Joseph A

2005-07-01

Ventricular hypertrophy develops in response to numerous forms of cardiac stress, including pressure or volume overload, loss of contractile mass from prior infarction, neuroendocrine activation, and mutations in genes encoding sarcomeric proteins. Hypertrophic growth is believed to have a compensatory role that diminishes wall stress and oxygen consumption, but Framingham and other studies established ventricular hypertrophy as a marker for increased risk of developing chronic heart failure, suggesting that hypertrophy may have maladaptive features. However, the relative contribution of comorbid disease to hypertrophy-associated systolic failure is unknown. For instance, coronary artery disease is induced by many of the same risk factors that cause hypertrophy and can itself lead to systolic dysfunction. It is uncertain, therefore, whether ventricular hypertrophy commonly progresses to systolic dysfunction without the contribution of intervening ischemia or infarction. In this review, we summarize findings from epidemiologic studies, preclinical experiments in animals, and clinical trials to lay out what is known-and not known-about this important question.

Value of the Electrocardiogram as a Predictor of Right Ventricular Dysfunction in Patients With Chronic Right Ventricular Volume Overload.

PubMed

Alonso, Pau; Andrés, Ana; Rueda, Joaquín; Buendía, Francisco; Igual, Begoña; Rodríguez, María; Osa, Ana; Arnau, Miguel A; Salvador, Antonio

2015-05-01

Pulmonary regurgitation is a common complication in patients with repaired tetralogy of Fallot or congenital pulmonary stenosis. Electrocardiographic variables have been correlated with parameters used to evaluate right ventricular function. We aimed to analyze the diagnostic value of the width and fragmentation of the electrocardiogram in the identification of patients with right ventricular dysfunction and/or dilation. We selected 107 consecutive patients diagnosed with severe pulmonary insufficiency after repair of pulmonary stenosis or tetralogy of Fallot. The tests included electrocardiography, echocardiography, and magnetic resonance. Each electrocardiogram was analyzed manually to measure QRS duration. We defined QRS fragmentation as the presence of low-voltage waves in the terminal portion of the QRS complex in at least 2 contiguous leads. We found a significant negative correlation between QRS width and right ventricular function, as well as a positive correlation with right ventricular volume. The receiver operating characteristic curve indicated a cut-off point for QRS width of 140ms, which showed good sensitivity for a diagnosis of right ventricular dilation (> 80%) and dysfunction (> 95%). In logistic regression models, a QRS duration > 140ms was found to be the only independent predictor of right ventricular dilation and dysfunction. Electrocardiography is a rapid, widely available, and reproducible tool. QRS width constitutes an independent predictor of the presence of right ventricular dilation and dysfunction. This study is the first to provide a cutoff value for QRS width to screen for right ventricle involvement. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Tricuspid Regurgitation Does Not Impact Right Ventricular Remodeling After Percutaneous Pulmonary Valve Implantation.

PubMed

Tanase, Daniel; Ewert, Peter; Georgiev, Stanimir; Meierhofer, Christian; Pabst von Ohain, Jelena; McElhinney, Doff B; Hager, Alfred; Kühn, Andreas; Eicken, Andreas

2017-04-10

This study sought to investigate the impact of tricuspid regurgitation (TR) on right ventricular function after percutaneous pulmonary valve implantation (PPVI). PPVI provides a less invasive alternative to surgery in patients with right ventricular-to-pulmonary artery (RV-PA) conduit dysfunction. Recovery of the right ventricle has been described after PPVI for patients with pulmonary stenosis and for those with pulmonary regurgitation. Additional TR enforces RV dysfunction by supplemental volume overload. Limited data are available on the potential of the right ventricle to recover in such a specific hemodynamic situation. In a matched cohort study, we compared patients who underwent PPVI with additional TR with those without TR. The degree of TR improved in 83% of the patients. In our patients (n = 36) exercise capacity and right ventricular volume index improved similarly 6 months after PPVI in patients with and without important TR. None of them had significant TR in the long-term follow-up of median 78 months. PPVI improves not only RV-PA-conduit dysfunction, but also concomitant TR. In patients with a dysfunctional RV-PA conduit and TR, the decision whether to fix TR should be postponed after PPVI. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Model-specific selection of molecular targets for heart failure gene therapy

PubMed Central

Katz, Michael G.; Fargnoli, Anthony S.; Tomasulo, Catherine E.; Pritchette, Louella A.; Bridges, Charles R.

2013-01-01

Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca2+ handling proteins and angiogenesis in the most common extrinsic models of HF. PMID:21954055

Diagnostic accuracy of an ultrasonic multiple transducer cardiac imaging system

NASA Technical Reports Server (NTRS)

Popp, R. L.; Brown, O. R.; Harrison, D. C.

1975-01-01

An ultrasonic multiple-transducer imaging system for intracardiac structure visualization is developed in order to simplify visualization of the human heart in vivo without radiation hazard or invasion of the body. Results of the evaluation of the diagnostic accuracy of the devised system in a clinical setting for adult patients are presented and discussed. Criteria are presented for recognition of mitral valva prolapse, mitral stenosis, pericardial effusion, atrial septal defect, and left ventricular dyssynergy. The probable cause for false-positive and false-negative diagnoses is discussed. However, hypertrophic myopathy and congestive myopathy were unable to be detected. Since only qualitative criteria were used, it was not possible to differentiate patients with left ventricular volume overload from patients without cardiac pathology.

Right ventricular effects of intracoronary delivery of mesenchymal stem cells (MSC) in an animal model of pressure overload heart failure.

PubMed

Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Gaughan, John P; Houser, Steven; Macha, Mahender

2009-12-01

In a rat model of left ventricular pressure overload hypertrophy with biventricular failure, we studied the effects of intracoronary delivery of mesenchymal stem cells (MCS) upon right ventricular hemodynamic performance, profiles of local inflammation and apoptosis, and determinants of extracellular matrix remodeling. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After a decrease in left ventricular fractional shortening of 25% from the baseline (relative 50% reduction), animals were randomized to an intracoronary injection of MSC (n=28) or PBS (n=20). Right ventricular hemodynamic assessment and measurement of local inflammatory markers, proapoptotic factors, and determinants of extracellular matrix remodeling were performed on post-transplantation day 7, 14, 21 or 28. MSC injection improved right ventricular systolic function in the MSC group compared to the control group (mean+/-SD, max dP/dt 772+/-272 mm Hg/s vs. 392+/-132 at 28 days, P<0.01). Diastolic function was similarly improved (mean+/-SD, max -dP/dt -558+/-171 mm Hg/s vs. -327+/-131 at 28 days, P<0.05). Right ventricular levels of IL-1, IL-6, TNF-alpha, bax, bak and p38 were significantly decreased in the MSC treated animals. Expression of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 declined in the MSC group compared with controls after 28 days. In this model of left ventricular pressure overload hypertrophy and biventricular failure, intracoronary delivery of MSC was associated with an improvement in the right ventricular hemodynamic performance, profiles of local inflammation and apoptosis, and determinants of extracellular matrix remodeling.

Pressure overload differentially affects respiratory capacity in interfibrillar and subsarcolemmal mitochondria.

PubMed

Schwarzer, Michael; Schrepper, Andrea; Amorim, Paulo A; Osterholt, Moritz; Doenst, Torsten

2013-02-15

Years ago a debate arose as to whether two functionally different mitochondrial subpopulations, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), exist in heart muscle. Nowadays potential differences are often ignored. Presumably, SSM are providing ATP for basic cell function, whereas IFM provide energy for the contractile apparatus. We speculated that two distinguishable subpopulations exist that are differentially affected by pressure overload. Male Sprague-Dawley rats were subjected to transverse aortic constriction for 20 wk or sham operation. Contractile function was assessed by echocardiography. Heart tissue was analyzed by electron microscopy. Mitochondria were isolated by differential centrifugation, and respiratory capacity was analyzed using a Clark electrode. Pressure overload induced left ventricular hypertrophy with increased posterior wall diameter and impaired contractile function. Mitochondrial state 3 respiration in control was 50% higher in IFM than in SSM. Pressure overload significantly impaired respiratory rates in both IFM and SSM, but in SSM to a lower extent. As a result, there were no differences between SSM and IFM after 20 wk of pressure overload. Pressure overload reduced total citrate synthase activity, suggesting reduced total mitochondrial content. Electron microscopy revealed normal morphology of mitochondria but reduced total mitochondrial volume density. In conclusion, IFM show greater respiratory capacity in the healthy rat heart and a greater depression of respiratory capacity by pressure overload than SSM. The differences in respiratory capacity of cardiac IFM and SSM in healthy hearts are eliminated with pressure overload-induced heart failure. The strong effect of pressure overload on IFM together with the simultaneous appearance of mitochondrial and contractile dysfunction may support the notion of IFM primarily producing ATP for contractile function.

Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

NASA Technical Reports Server (NTRS)

Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

2000-01-01

BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

Inhibition of soluble epoxide hydrolase does not improve the course of congestive heart failure and the development of renal dysfunction in rats with volume overload induced by aorto-caval fistula

PubMed Central

Červenka, Luděk; Melenovský, Vojtěch; Husková, Zuzana; Sporková, Alexandra; Bürgelová, Marcela; Škaroupková, Petra; Hwang, Sung Hee; Hammock, Bruce D.; Imig, John D.; Sadowski, Janusz

2016-01-01

The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/L in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/L in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume overload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin-angiotensin system in the circulating blood and kidney tissue. PMID:26047375

Monitoring of Cardiac Remodeling in a Mouse Model of Pressure-Overload Left Ventricular Hypertrophy with [18F]FDG MicroPET.

PubMed

Todica, Andrei; Beetz, Nick L; Günther, Lisa; Zacherl, Mathias J; Grabmaier, Ulrich; Huber, Bruno; Bartenstein, Peter; Brunner, Stefan; Lehner, Sebastian

2018-04-01

This study aims to analyze the left ventricular function parameters, scar load, and hypertrophy in a mouse model of pressure-overload left ventricular (LV) hypertrophy over the course of 8 weeks using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) micro-positron emission tomography (microPET) imaging. LV hypertrophy was induced in C57BL/6 mice by transverse aortic constriction (TAC). Myocardial hypertrophy developed after 2-4 weeks. ECG-gated microPET scans with [ 18 F]FDG were performed 4 and 8 weeks after surgery. The extent of fibrosis was measured by histopathologic analysis. LV function parameters and scar load were calculated using QGS®/QPS®. LV metabolic volume (LVMV) and percentage injected dose per gram were estimated by threshold-based analysis. The fibrotic tissue volume increased significantly from 4 to 8 weeks after TAC (​1.67 vs. 3.91  mm 3 ; P = 0.044). There was a significant increase of the EDV (4 weeks: 54 ± 15 μl, 8 weeks: 79 ± 32 μl, P < 0.01) and LVMV (4 weeks: 222 ± 24 μl, 8 weeks: 276 ± 52 μl, P < 0.01) as well as a significant decrease of the LVEF (4 weeks: 56 ± 17 %, 8 weeks: 44 ± 20 %, P < 0.01). The increase of LVMV had a high predictive value regarding the amount of ex vivo measured fibrotic tissue (R = 0.905, P < 0.001). The myocardial metabolic defects increased within 4 weeks (P = 0.055) but only moderately correlated with the fibrosis volume (R = 0.502, P = 0.021). The increase in end-diastolic volume showed a positive correlation with the fibrosis at 8 weeks (R = 0.763, P = 0.017). [ 18 F]FDG-PET is applicable for serial in vivo monitoring of the TAC mouse model. Myocardial hypertrophy, the dilation of the left ventricle, and the decrease in LVEF could be reliably quantified over time, as well as the developing localized scar. The increase in volume over time is predictive of a high fibrosis load.

[Sedation and anesthesia in dogs and cats with cardiovascular disease. II. Anesthesia planning with respect to pathophysiology, heart arrhythmia].

PubMed

Skarda, R T; Muir, W W; Bednarski, R M; Hubbell, J A; Mason, D E

1995-01-01

The purpose of this study was to review the incidence of cardiac arrhythmias in 137 anesthetized dogs and 13 anesthetized cats with congenital or acquired heart disease that were referred for correction of following procedures: patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch (ring anomaly, 3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart base tumor (2%), and palliative surgery for ventricular septal defect (VSD, 0.7%). The anesthetic plan considered the risks of anesthesia based upon the pathophysiology of cardiac lesions and the anesthetic drug effects on the cardiovascular system. Recommendations are made for dogs with decreased cardiac contractility, cardiac disease with volume overload, cardiac disease with pressure overload, and pericardial tamponade. The percentages of animals and their associated cardiac arrhythmias after premedication and during and after anesthesia were: sinus bradycardia (15.3%), sinus tachycardia (3.3%), atrial flutter (0.7%), atrial fibrillation (0.7%), premature ventricular contraction (14%), and ventricular tachycardia (1.3%). Prompt therapy was given to a percentage of animals in order to control arrhythmia and support cardiovascular system, by using atropine or glycopyrrolate (14%), lidocaine (17.3%), and dopamine (14.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

LRRC10 is required to maintain cardiac function in response to pressure overload.

PubMed

Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

2016-01-15

We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. Copyright © 2016 the American Physiological Society.

Prevention of ventricular arrhythmia and calcium dysregulation in a catecholaminergic polymorphic ventricular tachycardia mouse model carrying calsequestrin-2 mutation.

PubMed

Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G; Seidman, Christine E; Berul, Charles I

2011-03-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca(2+) overload and increased Ca(2+) leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. CPVT mouse models that lack CASQ2 were treated with Ca(2+) -channel inhibitors, β-adrenergic inhibitors, or Mg(2+) . Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca(2+) transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca(2+) channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca(2+) content in mutant myocytes, diminished diastolic Ca(2+) overload, increased systolic Ca(2+) amplitude, and prevented Ca(2+) oscillations in stressed mutant myocytes. Ca(2+) channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca(2+) content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca(2+) buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. © 2010 Wiley Periodicals, Inc.

Prevention of Ventricular Arrhythmia and Calcium Dysregulation in a Catecholaminergic Polymorphic Ventricular Tachycardia Mouse Model Carrying Calsequestrin-2 Mutation

PubMed Central

Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G.; Seidman, Christine E.; Berul, Charles I

2010-01-01

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca2+ overload and increased Ca2+ leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. Method and results CPVT mouse models that lack CASQ2 were treated with Ca2+-channel inhibitors, β-adrenergic inhibitors, or Mg2+. Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca2+ transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca2+ channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca2+ content in mutant myocytes, diminished diastolic Ca2+ overload, increased systolic Ca2+ amplitude, and prevented Ca2+ oscillations in stressed mutant myocytes. Conclusions Ca2+ channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca2+ content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca2+ buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. PMID:20807279

Quantitative analysis of collagens and fibronectin expression in human right ventricular hypertrophy.

PubMed

Peters, T H; Sharma, H S; Yilmaz, E; Bogers, A J

1999-06-30

One of the main features in human tetralogy of Fallot (TF) is right ventricular hypertrophy (RVH) due to pressure (sub-pulmonary stenosis) and volume overload (ventricular septal defect). Currently, primary correction at a young age is the treatment of choice. To unravel the role of extracellular matrix in RVH, we examined myocardial expression of collagens and fibronectin in TF patients with primary correction (TF1, age 0.7 +/- 0.2 yr.), secondary surgery (TF2, age 36.9 +/- 4.6 yr), and in age-matched control patients. Sirius red staining quantified by video imaging showed significantly increased interstitial staining for collagens in both TF1 and TF2 groups as compared to respective controls. Fibronectin was expressed in extracellular spaces, perivascular regions, and in some cardiomyocytes. Quantitative analysis of fibronectin revealed increased expression in only TF1 group as compared to respective control. Our results indicate an increased amount of myocardial extracellular matrix deposition as a sign of fibrosis during RVH in patients with TF.

LRRC10 is required to maintain cardiac function in response to pressure overload

PubMed Central

Brody, Matthew J.; Feng, Li; Grimes, Adrian C.; Hacker, Timothy A.; Olson, Timothy M.; Kamp, Timothy J.

2015-01-01

We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10−/−) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10−/− mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10−/− mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10−/− cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His150 of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. PMID:26608339

Substance P induces adverse myocardial remodelling via a mechanism involving cardiac mast cells.

PubMed

Meléndez, Giselle C; Li, Jianping; Law, Brittany A; Janicki, Joseph S; Supowit, Scott C; Levick, Scott P

2011-12-01

Substance P and neurokinin A (NKA) are sensory nerve neuropeptides encoded by the TAC1 gene. Substance P is a mast cell secretagogue and mast cells are known to play a role in adverse myocardial remodelling. Therefore, we wondered whether substance P and/or NKA modulates myocardial remodelling via a mast cell-mediated mechanism. Volume overload was induced by aortocaval fistula in TAC1(-/-) mice and their respective wild types. Left ventricular internal diameter of wild-type (WT) fistulas increased by 31.9%; this was prevented in TAC1(-/-) mice (4.2%). Matrix metalloproteinase (MMP) activity was significantly increased in WT fistula mice and was prevented in TAC1(-/-) mice. Myocardial collagen volume fraction was decreased in WT fistula mice; this collagen degradation was not observed in the TAC1(-/-) group. There were no significant differences between any groups in tumour necrosis factor (TNF)-α or cell death. Cardiac mast cells were isolated from rat hearts and stimulated with substance P or NKA. We found that these cells degranulated only to substance P, via the neurokinin-1 receptor. To determine the effect of substance P on mast cells in vivo, volume overload was created in Sprague-Dawley rats treated with the NK-1 receptor antagonist L732138 (5 mg/kg/day) for a period of 3 days. L732138 prevented: (i) increases in cardiac mast cell density; (ii) increased myocardial TNF-α; and (iii) collagen degradation. Our studies suggest that substance P may be important in mediating adverse myocardial remodelling secondary to volume overload by activating cardiac mast cells, leading to increased TNF-α and MMP activation with subsequent degradation of the extracellular matrix.

Substance P induces adverse myocardial remodelling via a mechanism involving cardiac mast cells

PubMed Central

Meléndez, Giselle C.; Li, Jianping; Law, Brittany A.; Janicki, Joseph S.; Supowit, Scott C.; Levick, Scott P.

2011-01-01

Aims Substance P and neurokinin A (NKA) are sensory nerve neuropeptides encoded by the TAC1 gene. Substance P is a mast cell secretagogue and mast cells are known to play a role in adverse myocardial remodelling. Therefore, we wondered whether substance P and/or NKA modulates myocardial remodelling via a mast cell-mediated mechanism. Methods and results Volume overload was induced by aortocaval fistula in TAC1−/− mice and their respective wild types. Left ventricular internal diameter of wild-type (WT) fistulas increased by 31.9%; this was prevented in TAC1−/− mice (4.2%). Matrix metalloproteinase (MMP) activity was significantly increased in WT fistula mice and was prevented in TAC1−/− mice. Myocardial collagen volume fraction was decreased in WT fistula mice; this collagen degradation was not observed in the TAC1−/− group. There were no significant differences between any groups in tumour necrosis factor (TNF)-α or cell death. Cardiac mast cells were isolated from rat hearts and stimulated with substance P or NKA. We found that these cells degranulated only to substance P, via the neurokinin-1 receptor. To determine the effect of substance P on mast cells in vivo, volume overload was created in Sprague-Dawley rats treated with the NK-1 receptor antagonist L732138 (5 mg/kg/day) for a period of 3 days. L732138 prevented: (i) increases in cardiac mast cell density; (ii) increased myocardial TNF-α; and (iii) collagen degradation. Conclusions Our studies suggest that substance P may be important in mediating adverse myocardial remodelling secondary to volume overload by activating cardiac mast cells, leading to increased TNF-α and MMP activation with subsequent degradation of the extracellular matrix. PMID:21908647

Molecular Mechanisms of Right Ventricular Failure

PubMed Central

Reddy, Sushma; Bernstein, Daniel

2015-01-01

An abundance of data has provided insight into the mechanisms underlying the development of left ventricular (LV) hypertrophy and its progression to LV failure. In contrast, there is minimal data on the adaptation of the right ventricle (RV) to pressure and volume overload and the transition to RV failure. This is a critical clinical question, as the RV is uniquely at risk in many patients with repaired or palliated congenital heart disease and in those with pulmonary hypertension. Standard heart failure therapies have failed to improve function or survival in these patients, suggesting a divergence in the molecular mechanisms of RV vs. LV failure. Although, on the cellular level, the remodeling responses of the RV and LV to pressure overload are largely similar, there are several key differences: the stressed RV is more susceptible to oxidative stress, has a reduced angiogenic response, and is more likely to activate cell death pathways than the stressed LV. Together, these differences could explain the more rapid progression of the RV to failure vs. the LV. This review will highlight known molecular differences between the RV and LV responses to hemodynamic stress, the unique stressors on the RV associated with congenital heart disease, and the need to better understand these molecular mechanisms if we are to develop RV-specific heart failure therapeutics. PMID:26527692

Impact of Volume Management on Volume Overload and Rehospitalization in CAPD Patients.

PubMed

Xu, Yi; Yang, Shen-Min; Wang, Xiao-Hua; Wang, Hai-Fang; Niu, Mei-E; Yang, Yi-Qun; Lu, Guo-Yuan; Pang, Jian-Hong; Wang, Fei; Li, Lin

2018-05-01

Heart failure due to volume overload is a major reason for rehospitalization in continuous ambulatory peritoneal dialysis patients. Strict volume control provides better cardiac functions and blood pressure in this population. Volume management, which is a volume control strategy, may decrease volume overload and related complications. Using a quasi-experimental design, 66 continuous ambulatory peritoneal dialysis patients were randomly assigned to the intervention group ( n = 34) and control group ( n = 32). The patients were followed up for 6 months with scheduled clinic and/or telephone visits; the intervention group adopted volume management strategy, while the control group adopted conventional care. Volume overload and cardiac function were compared between the two groups at the baseline and at 6 months. At Month 6, the intervention group resulted in significant improvement in volume overloaded status, cardiac function, and volume-overload-related rehospitalization. Volume management strategy allows for better control of volume overload and is associated with fewer volume-related readmissions.

Occult constrictive pericardial disease emerging 40 years after chest radiation therapy: a case report.

PubMed

Goten, Chiaki; Murai, Hisayoshi; Takashima, Shin-Ichiro; Kato, Takeshi; Usui, Soichiro; Furusho, Hiroshi; Saeki, Takahiro; Sakagami, Satoru; Takemura, Hirofumi; Kaneko, Shuichi; Takamura, Masayuki

2018-05-31

The main etiology of constrictive pericarditis (CP) has changed from tuberculosis to therapeutic mediastinal radiation and cardiac surgery. Occult constrictive pericardial disease (OCPD) is a covert disease in which CP is manifested in a condition of volume overload. A 60-year-old patient with a history of thoracic radiation therapy for non-Hodgkin's lymphoma (40 years earlier) was transferred to our hospital for treatment of repeated congestive heart failure. For a preoperative hemodynamic study, pre-hydration with intravenous normal saline (50 mL/hour) was used to manifest the pericardial disease and prevent contrast-induced nephropathy. The hemodynamic study showed a right ventricular dip-plateau pattern and discordance of right and left ventricular systolic pressures during inspiration, which was not seen in the volume-controlled state. These responses were concordant with OCPD. A pericardiectomy, aortic valve replacement, and mitral and tricuspid valve repair were performed. Postoperatively, the heart failure was controlled with standard medication. This case revealed a volume-induced change in hemodynamics in OCPD with severe combined valvular heart disease, which suggests the importance of considering OCPD in patients who had undergone radiation therapy 40 years before.

Inhibitor of lysyl oxidase improves cardiac function and the collagen/MMP profile in response to volume overload.

PubMed

El Hajj, Elia C; El Hajj, Milad C; Ninh, Van K; Gardner, Jason D

2018-05-18

The cardiac extracellular matrix is a complex architectural network that serves many functions including providing structural and biochemical support to surrounding cells, and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of the pro-inflammatory and pro-fibrotic responses induce a vicious cycle which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix. Further, excess synthesis and activation of the enzyme lysyl oxidase (LOX) during disease increases collagen cross-linking, which significantly increases collagen resistance to degradation by matrix metalloproteinases (MMPs). In this study, the aortocaval fistula model of volume overload (VO) was used to determine whether LOX inhibition could prevent adverse changes in the ECM and subsequent cardiac dysfunction. The major findings from this study are that LOX inhibition: (a) prevented VO-induced increases in LV wall stress, (b) partially attenuated VO-induced ventricular hypertrophy, (c) completely blocked the increases in fibrotic proteins, including collagens, MMPs, and their tissue inhibitors (TIMPs), and (d) prevented the VO-induced decline in cardiac function. It remains unclear whether a direct interaction between LOX and MMPs exists; however our studies suggest a potential link between the two since LOX inhibition completely attenuated the VO-induced increases in MMPs. Overall, our studies demonstrate key cardioprotective effects of LOX inhibition against adverse cardiac remodeling due to chronic VO.

Microtubule Stabilization in Pressure Overload Cardiac Hypertrophy

PubMed Central

Sato, Hiroshi; Nagai, Toshio; Kuppuswamy, Dhandapani; Narishige, Takahiro; Koide, Masaaki; Menick, Donald R.; IV, George Cooper

1997-01-01

Increased microtubule density, for which microtubule stabilization is one potential mechanism, causes contractile dysfunction in cardiac hypertrophy. After microtubule assembly, α-tubulin undergoes two, likely sequential, time-dependent posttranslational changes: reversible carboxy-terminal detyrosination (Tyr-tubulin ↔ Glu-tubulin) and then irreversible deglutamination (Glu-tubulin → Δ2-tubulin), such that Glu- and Δ2-tubulin are markers for long-lived, stable microtubules. Therefore, we generated antibodies for Tyr-, Glu-, and Δ2-tubulin and used them for staining of right and left ventricular cardiocytes from control cats and cats with right ventricular hypertrophy. Tyr- tubulin microtubule staining was equal in right and left ventricular cardiocytes of control cats, but Glu-tubulin and Δ2-tubulin staining were insignificant, i.e., the microtubules were labile. However, Glu- and Δ2-tubulin were conspicuous in microtubules of right ventricular cardiocytes from pressure overloaded cats, i.e., the microtubules were stable. This finding was confirmed in terms of increased microtubule drug and cold stability in the hypertrophied cells. In further studies, we found an increase in a microtubule binding protein, microtubule-associated protein 4, on both mRNA and protein levels in pressure-hypertrophied myocardium. Thus, microtubule stabilization, likely facilitated by binding of a microtubule-associated protein, may be a mechanism for the increased microtubule density characteristic of pressure overload cardiac hypertrophy. PMID:9362514

Left ventricular rotation and torsion in patients with perimembranous ventricular septal defect.

PubMed

Zhuang, Yan; Yong, Yong-hong; Yao, Jing; Ji, Ling; Xu, Di

2014-03-01

Assessment of left ventricular (LV) rotation has become an important approach for quantifying LV function. In this study, we sought to analyze LV rotation and twist using speckle tracking imaging (STI) in adult patients with isolated ventricular septal defects. Using STI, the peak rotation and time to peak rotation of 6 segments in basal and apical short-axis were measured, respectively, in 32 patients with ventricular septal defect and 30 healthy subjects as controls. The global rotation of the 6 segments in basal and apical and LV twist versus time profile were drawn, the peak rotation and twist of LV were calculated. All the time to peak rotation/twist were expressed as a percentage of end-systole (end-systole = 100%). Left ventricular ejection fraction was measured by biplane Simpson method. In patients group, the peak rotation of posterior, inferior, and postsept wall in basal was higher(P ≤ 0.05) and LV twist was also higher (P ≤ 0.05) than healthy controls. There were no significant differences between 2 groups in the peak rotation of the other 9 segments and left ventricular ejection fraction. Different from the control group, the time to peak rotation of the 6 segments in basal were delayed and the global rotation of the base was delayed (P ≤ 0.05) in ventricular septal defect group. Left ventricular volume overload due to ventricular septal defect has significant effect on LV rotation and twist, and LV rotation and twist may be a new index predicting LV systolic function. © 2013, Wiley Periodicals, Inc.

Estrogenic modulation of inflammation-related genes in male rats following volume overload

PubMed Central

McLarty, Jennifer L.; Meléndez, Giselle C.; Levick, Scott P.; Bennett, Shanté; Sabo-Attwood, Tara; Brower, Gregory L.

2012-01-01

Our laboratory has previously reported significant increases of the proinflammatory cytokine TNF-α in male hearts secondary to sustained volume overload. These elevated levels of TNF-α are accompanied by left ventricular (LV) dilatation and cardiac dysfunction. In contrast, estrogen has been shown to protect against this adverse cardiac remodeling in both female and male rats. The purpose of this study was to determine whether estrogen has an effect on inflammation-related genes that contribute to this estrogen-mediated cardioprotection. Myocardial volume overload was induced by aortocaval fistula in 8 wk old male Sprague-Dawley rats (n = 30), and genes of interest were identified using an inflammatory PCR array in Sham, Fistula, and Fistula + Estrogen-treated (0.02 mg/kg per day beginning 2 wk prior to fistula) groups. A total of 55 inflammatory genes were modified (≥2-fold change) at 3 days postfistula. The number of inflammatory gene was reduced to 21 genes by estrogen treatment, whereas 13 genes were comparably modulated in both fistula groups. The most notable were TNF-α, which was downregulated by estrogen, and the TNF-α receptors, which were differentially regulated by estrogen. Specific genes related to arachidonic acid metabolism were downregulated by estrogen, including cyclooxygenase-1 and -2. Finally, gene expression for the β1-integrin cell adhesion subunit was significantly upregulated in the LV of estrogen-treated animals. Protein levels reflected the changes observed at the gene level. These data suggest that estrogen provides its cardioprotective effects, at least in part, via genomic modulation of numerous inflammation-related genes. PMID:22274565

Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy.

PubMed

Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender

2008-02-01

In a rat model of pressure overload hypertrophy, we studied the effects of intracoronary delivery of mesenchymal stem cells on hemodynamic performance, exercise capacity, systemic inflammation, and left ventricular reverse remodeling. Sprague-Dawley rats underwent aortic banding and were followed up by echocardiographic scanning. After a decrease in fractional shortening of 25% from baseline, animals were randomized to intracoronary injection of mesenchymal stem cells (MSC group; n = 28) or phosphate-buffered saline solution (control group; n = 20). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of inflammatory markers were performed before the rats were humanely killed on postoperative day 7, 14, 21, or 28. Injection of mesenchymal stem cells improved systolic function in the MSC group compared with the control group (mean +/- standard deviation: maximum dP/dt 3048 +/- 230 mm Hg/s vs 2169 +/- 97 mm Hg/s at 21 days and 3573 +/- 741 mm Hg/s vs 1363 +/- 322 mm Hg/s at 28 days: P < .001). Time to exhaustion was similarly increased in the MSC group compared with controls (487 +/- 35 seconds vs 306 +/- 27 seconds at 28 days; P < .01). Serum levels of interleukins 1 and 6, tumor necrosis factor-alpha, and brain natriuretic peptide-32 were significantly decreased in animals treated with mesenchymal stem cells. Stem cell transplantation improved left ventricular fractional shortening at 21 and 28 days. Left ventricular end-systolic and end-diastolic diameters were also improved at 28 days. In this model of pressure overload hypertrophy, intracoronary delivery of mesenchymal stem cells during heart failure was associated with an improvement in hemodynamic performance, maximal exercise tolerance, systemic inflammation, and left ventricular reverse remodeling. This study suggests a potential role of this treatment strategy for the management of hypertrophic heart failure resulting from pressure overload.

Volume Overload: Prevalence, Risk Factors, and Functional Outcome in Survivors of Septic Shock

PubMed Central

Carlbom, David; Caldwell, Ellen; Himmelfarb, Jonathan; Hough, Catherine L.

2015-01-01

Rationale: Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown. Objectives: This study describes patterns of fluid management both during and after septic shock. We examined factors associated with volume overload upon intensive care unit (ICU) discharge. We then examined associations between volume overload upon ICU discharge, mobility limitation, and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes. Methods: We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital between June 2009 and April 2012 who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subject’s admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression. Measurements and Main Results: Eighty-six percent of patients had a positive fluid balance, and 35% had volume overload upon ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.33–5.27; P = 0.01) after adjusting for preexisting conditions and severity of illness. Only 42% of patients received at least one dose of a diuretic during their hospitalization. Volume overload upon ICU discharge was independently associated with inability to ambulate upon hospital discharge (OR, 2.29; 95% CI, 1.24–4.25; P = 0.01) and, in patients admitted from home, upon discharge to a healthcare facility (OR, 2.34; 95% CI, 1.1–4.98; P = 0.03). Conclusions: Volume overload is independently associated with impaired mobility and discharge to a healthcare facility in survivors of septic shock. Prevention and treatment of volume overload in patients with septic shock warrants further investigation. PMID:26394090

Functional and geometrical interference and interdependency between the right and left ventricle in cor pulmonale: an experimental study on simultaneous measurement of biventricular geometry of acute right ventricular pressure overload.

PubMed

Yamashita, H; Onodera, S; Imamoto, T; Obara, A; Tanazawa, S; Takashio, T; Morimoto, H; Inoue, H

1989-10-01

To clarify the effects of right ventricular (RV) pressure overload on functional and geometrical interference and interdependency between the right and left ventricle, both ventricular internal diameters were measured by the microcrystal technique during lycopodium induced pulmonary embolization in the dog. By repeated embolization, RV systolic pressure was increased progressively until it reached a peak value of about 60-70 mmHg, then it began to fall. At the same time, the hemodynamics deteriorated progressively resulting in death. During the experiment, gradual leftward displacement of the interventricular septum (IVS) without any change in left ventricular (LV) free wall geometry was observed. In pulmonary embolic shock, which showed a fall in LV pressure to about 60 mmHg and cardiac output to about 40% of control, the leftward displacement of IVS became marked, and the cooperative movement of IVS to LV contraction disappeared. The IVS position during acute RV pressure overload was able to account for the transseptal pressure gradient. The importance of IVS position and motion in cardiac function during acute RV pressure overload was stressed. Furthermore, to establish the theoretical treatment in acute cardiopulmonary resuscitation, ligation of the descending aorta (AoL) or norepinephrine ("N") or isoproterenol ("I") administration were examined in a canine pulmonary embolic shock model. AoL or "N" improved the deteriorated hemodynamics with restoration of biventricular geometry. However, "I" did not restore the biventricular geometry despite the transiently improved hemodynamics, and the experimental animals were unable to survive. These results suggest the importance of the maintainance of systemic pressure for the restoration of failed RV function. Further integrated studies are required to understand biventricular interference and interdependency.

Ruptured congenital aneurysm of the right sinus of Valsalva into the right ventricle: with special reference to pathoanatomic and hemodynamic characteristics in symptomless cases.

PubMed

Chen, J J; Lien, W P; Chang, F Z; Lee, Y S; Hung, C R; Chu, S S; Wu, T L

1980-02-01

Clinical features of 19 cases with congenital aneurysm of the right sinus of Valsalva rupturing into the right ventricular outflow region (Type 1) were analysed in relation to their pathoanatomic lesions and hemodynamic alterations. Sixteen cases were operated with one surgical death. All were catheterized together with ascending aortographic study. Rupture of the aneurysm in many cases was silent or symptomless and progressive heart failure was not quite common. Symptomatology of the patients did not seem to be related entirely to status of the pathoanatomical lesions or hemodynamic alterations. Time of the rupture, and inherent right ventricular characteristics, tolerating volume overload rather well, might be, in part, responsible for its better prognosis in some cases. However, all patients with ruptured aneurysm of the sinus of Valsalva should be treated surgically. Bacterial endocarditis is a serious complication leading to death.

Effects of hawthorn on cardiac remodeling and left ventricular dysfunction after 1 month of pressure overload-induced cardiac hypertrophy in rats.

PubMed

Hwang, Hyun Seok; Bleske, Barry E; Ghannam, Michael M J; Converso, Kimber; Russell, Mark W; Hunter, James C; Boluyt, Marvin O

2008-02-01

Hawthorn (Crataegus) is a natural product used to treat patients with heart failure. The effects of hawthorn on cardiac remodeling, however, are not known. The purpose was to determine the effects of hawthorn treatment on remodeling and function of the left ventricle (LV) after 1 month of pressure overload-induced cardiac hypertrophy. Sprague-Dawley rats (male, 300 g) were subjected to sham operation (SH) or aortic constriction (AC) for 4 weeks and treated with Hawthorn (Crataegus-Extract- WS1442;1.3, 13, 130 mg kg(-1) day(-1); AC-L, AC-M, AC-H) or vehicle (SH-V, AC-V) for 3 weeks after surgery. Systolic and diastolic function were measured using echocardiographic assessment at baseline and 4 weeks after AC. AC increased the LV/body weight ratio by 34% in vehicle and hawthorn treated rats. Hawthorn markedly reduced LV chamber volumes (VOL) after AC [systolic VOL, mean +/- SEM, mm(3): SH-V, 87 +/- 13; AC-V, 93 +/- 12; AC-L, 62 +/- 9; AC-M, 68 +/- 12; AC-H; 50 +/- 11 and diastolic VOL: SH-V, 433 +/- 45; AC-V, 412 +/- 57; AC-L, 313 +/- 25; AC-M, 319 +/- 37; AC-H, 264 +/- 25 (p < 0.05)] and augmented relative wall thickness, mm: SH-V, 0.45 +/- 0.02; AC-V, 0.65 +/- 0.05; AC-L, 0.71 +/- 0.03; AC-M, 0.74 +/- 0.06; AC-H, 0.80 +/- 0.09 (p < 0.05). AC reduced velocity of circumferential shortening (Vcf(c)) by 28% compared with SH-V. Hawthorn attenuated the AC-induced decrease in Vcf(c) (p < 0.05). Hawthorn treatment modifies left ventricular remodeling and counteracts myocardial dysfunction in early pressure overload-induced cardiac hypertrophy.

Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload.

PubMed

Apitz, Christian; Honjo, Osami; Humpl, Tilman; Li, Jing; Assad, Renato S; Cho, Mi Y; Hong, James; Friedberg, Mark K; Redington, Andrew N

2012-12-01

Chronic right ventricular (RV) pressure overload results in pathologic RV hypertrophy and diminished RV function. Although aortic constriction has been shown to improve systolic function in acute RV failure, its effect on RV responses to chronic pressure overload is unknown. Adjustable vascular banding devices were placed on the main pulmonary artery and descending aorta. In 5 animals (sham group), neither band was inflated. In 9 animals (PAB group), only the pulmonary arterial band was inflated, with adjustments on a weekly basis to generate systemic or suprasystemic RV pressure at 28 days. In 9 animals, both pulmonary arterial and aortic devices were inflated (PAB + AO group), the pulmonary arterial band as for the PAB group and the aortic band adjusted to increase proximal systolic blood pressure by approximately 20 mm Hg. Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment. Contractile performance was significantly improved in the PAB + AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB + AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin receptor type B, matrix metalloproteinase 9, and transforming growth factor β genes. Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic response in the pressure-overloaded RV. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Fluid imbalance

MedlinePlus

... up in the body. This is called fluid overload (volume overload). This can lead to edema (excess fluid in ... Water imbalance; Fluid imbalance - dehydration; Fluid buildup; Fluid overload; Volume overload; Loss of fluids; Edema - fluid imbalance; ...

Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy.

PubMed

Molina, Ezequiel J; Palma, Jon; Gupta, Dipin; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender

2009-02-01

Changes in ventricular extracellular matrix (ECM) composition of pressure overload hypertrophy determine clinical outcomes. The effects of mesenchymal stem cell (MSC) transplantation upon determinants of ECM composition in pressure overload hypertrophy have not been studied. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After an absolute decrease in fractional shortening of 25% from baseline, 1 x 10(6) MSC (n = 28) or PBS (n = 20) was randomly injected intracoronarily. LV protein analysis, including matrix metalloproteinases (MMP-2, MMP-3, MMP-6, MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3), was performed after sacrifice on postoperative day 7, 14, 21 or 28. Left ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 were demonstrated to be decreased in the MSC group compared with controls after 28 days. Expression of MMP-2 and TIMP-2 remained relatively stable in both groups. Successful MSCs delivery was confirmed by histological analysis and visualization of labelled MSCs. In this model of pressure overload hypertrophy, intracoronary delivery of MSCs during heart failure was associated with specific changes in determinants of ECM composition. LV reverse remodeling was associated with decreased ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3, which were upregulated in the control group as heart failure progressed. These effects were most significant at 28 days following injection. (c) 2008 John Wiley & Sons, Ltd.

Effects of hawthorn on the progression of heart failure in a rat model of aortic constriction.

PubMed

Hwang, Hyun Seok; Boluyt, Marvin O; Converso, Kimber; Russell, Mark W; Bleske, Barry E

2009-06-01

To determine the effects of hawthorn (Crataegus oxycantha) on left ventricular remodeling and function in pressure overload-induced heart failure in an animal model. Randomized, parallel, dose-ranging animal study. University research facility. Seventy-four male Sprague-Dawley rats; 44 were included in the final analysis. Rats underwent a sham operation or aortic constriction. Rats subjected to the sham operation were treated with vehicle (10% agar-agar), and those subjected to aortic constriction were treated with vehicle or hawthorn (C. oxycantha special extract WS 1442) 1.3, 13, or 130 mg/kg for 5 months. Rats and their hearts were weighed, and echocardiographic measurements were performed at baseline and at 2, 3, 4, and 5 months after aortic constriction. Protein expression for markers of fibrosis and for atrial natriuretic factor was also measured. Aortic constriction increased the left ventricular:body weight ratio by 53% in vehicle-treated rats; Hawthorn treatment did not significantly affect the aortic constriction-induced increase in this ratio. Left ventricular volumes and dimensions at systole and diastole significantly increased 5 months after aortic constriction compared with baseline in rats given vehicle (> 20% increase, p<0.05) but not in those given hawthorn 130 mg/kg (< 10% increase). After aortic constriction, the velocity of circumferential shortening significantly decreased in the vehicle group but not in the medium- or high-dose groups. In the aortic constriction-vehicle group, the induced increases in messenger RNA expression for atrial natriuretic factor (approximately 1000%) and fibronectin (approximately 80%) were significantly attenuated by high-dose hawthorn treatment by approximately 80% and 50%, respectively. Hawthorn treatment exhibited modest beneficial effects on cardiac remodeling and function during long-term, pressure overload-induced heart failure in rats.

Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig

PubMed Central

Beaumont, Eric; Wright, Gary L.; Southerland, Elizabeth M.; Li, Ying; Chui, Ray; KenKnight, Bruce H.; Armour, J. Andrew

2016-01-01

Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig.

PubMed

Beaumont, Eric; Wright, Gary L; Southerland, Elizabeth M; Li, Ying; Chui, Ray; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

2016-05-15

Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15-20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. Copyright © 2016 the American Physiological Society.

Crucial role of rho-kinase in pressure overload-induced right ventricular hypertrophy and dysfunction in mice.

PubMed

Ikeda, Shohei; Satoh, Kimio; Kikuchi, Nobuhiro; Miyata, Satoshi; Suzuki, Kota; Omura, Junichi; Shimizu, Toru; Kobayashi, Kenta; Kobayashi, Kazuto; Fukumoto, Yoshihiro; Sakata, Yasuhiko; Shimokawa, Hiroaki

2014-06-01

Right ventricular (RV) failure is the leading cause of death in various cardiopulmonary diseases, including pulmonary hypertension. It is generally considered that the RV is vulnerable to pressure overload as compared with the left ventricle (LV). However, as compared with LV failure, the molecular mechanisms of RV failure are poorly understood, and hence therapeutic targets of the disorder remain to be elucidated. Thus, we aimed to identify molecular therapeutic targets for RV failure in a mouse model of pressure overload. To induce pressure overload to respective ventricles, we performed pulmonary artery constriction or transverse aortic constriction in mice. We first performed microarray analysis and found that the molecules related to RhoA/Rho-kinase and integrin pathways were significantly upregulated in the RV with pulmonary artery constriction compared with the LV with transverse aortic constriction. Then, we examined the responses of both ventricles to chronic pressure overload in vivo. We demonstrated that compared with transverse aortic constriction, pulmonary artery constriction caused greater extents of mortality, Rho-kinase expression (especially ROCK2 isoform), and oxidative stress in pressure-overloaded RV, reflecting the weakness of the RV in response to pressure overload. Furthermore, mice with myocardial-specific overexpression of dominant-negative Rho-kinase showed resistance to pressure overload-induced hypertrophy and dysfunction associated with reduced oxidative stress. Finally, dominant-negative Rho-kinase mice showed a significantly improved long-term survival in both pulmonary artery constriction and transverse aortic constriction as compared with littermate controls. These results indicate that the Rho-kinase pathway plays a crucial role in RV hypertrophy and dysfunction, suggesting that the pathway is a novel therapeutic target of RV failure in humans. © 2014 American Heart Association, Inc.

Salt intake during pregnancy alters offspring's myocardial structure.

PubMed

Alves-Rodrigues, E N; Veras, M M; Rosa, K T; de Castro, I; Furukawa, L N S; Oliveira, I B; Souza, R M; Heimann, J C

2013-05-01

To evaluate the effects of low or high salt intake during pregnancy on left ventricle of adult male offspring. Low- (LS, 0.15%), normal- (NS, 1.3%) or high-salt (HS, 8% NaCl) diet was given to Wistar rats during pregnancy. During lactation all dams received NS as well as the offspring after weaning. To evaluate cardiac response to salt overload, 50% of each offspring group was fed a high-salt (hs, 4% NaCl) diet from the 21st to the 36th week of age (LShs, NShs, HShs). The remaining 50% was maintained on NS (LSns, NSns and HSns). Echocardiography was done at 20 and 30 weeks of age. Mean blood pressure (MBP), histology and left ventricular angiotensin II content (AII) were analyzed at 36 weeks of age. Interventricular septum, left ventricular posterior wall and relative wall thickness increased from the 20th to the 30th week of age only in HShs, cardiomyocyte mean volume was higher in HShs compared to NShs, LShs and HSns. AII and left ventricular fibrosis were not different among groups. HS during pregnancy programs adult male offspring to a blood pressure and angiotensin II independent concentric left ventricular hypertrophy, with no fibrosis, in response to a chronic high-salt intake. Copyright © 2011 Elsevier B.V. All rights reserved.

Tachycardia-Induced Right Heart Failure and Severe Tricuspid Regurgitation That Improved with Medication.

PubMed

Yang, Young Ae; Yang, Dong Heon; Kim, Hong Nyun; Kwon, Sang Hoon; Jang, Se Young; Bae, Myung Hwan; Lee, Jang Hoon; Chae, Shung Chull

2015-12-01

Secondary tricuspid regurgitation (TR) primarily develops due to left heart failure or primary pulmonary diseases. Tricuspid annular dilation, which is commonly caused by right ventricular volume and pressure overload followed by right ventricle dilation, is believed to be the main mechanism underlying secondary TR. It is reported that once the tricuspid annulus is dilated, its size cannot spontaneously return to normal, and it may continue to dilate. These reports also suggest the use of an aggressive surgical approach for secondary TR. In the present report, we describe a case of tachycardia-induced severe TR that was completely resolved without the need for surgery.

Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

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

Guo, Haipeng; Zhang, Xin; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan

Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It wasmore » demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin suppressed oxidative stress and the excess production of ROS. • Taxifolin blocked ERK1/2, JNK1/2 and Smad signaling pathways. • We reported that taxifolin had the potential to be a candidate for cardiac hypertrophy treatment.« less

Cardiomyocyte Ogt limits ventricular dysfunction in mice following pressure overload without affecting hypertrophy.

PubMed

Dassanayaka, Sujith; Brainard, Robert E; Watson, Lewis J; Long, Bethany W; Brittian, Kenneth R; DeMartino, Angelica M; Aird, Allison L; Gumpert, Anna M; Audam, Timothy N; Kilfoil, Peter J; Muthusamy, Senthilkumar; Hamid, Tariq; Prabhu, Sumanth D; Jones, Steven P

2017-05-01

The myocardial response to pressure overload involves coordination of multiple transcriptional, posttranscriptional, and metabolic cues. The previous studies show that one such metabolic cue, O-GlcNAc, is elevated in the pressure-overloaded heart, and the increase in O-GlcNAcylation is required for cardiomyocyte hypertrophy in vitro. Yet, it is not clear whether and how O-GlcNAcylation participates in the hypertrophic response in vivo. Here, we addressed this question using patient samples and a preclinical model of heart failure. Protein O-GlcNAcylation levels were increased in myocardial tissue from heart failure patients compared with normal patients. To test the role of OGT in the heart, we subjected cardiomyocyte-specific, inducibly deficient Ogt (i-cmOgt -/- ) mice and Ogt competent littermate wild-type (WT) mice to transverse aortic constriction. Deletion of cardiomyocyte Ogt significantly decreased O-GlcNAcylation and exacerbated ventricular dysfunction, without producing widespread changes in metabolic transcripts. Although some changes in hypertrophic and fibrotic signaling were noted, there were no histological differences in hypertrophy or fibrosis. We next determined whether significant differences were present in i-cmOgt -/- cardiomyocytes from surgically naïve mice. Interestingly, markers of cardiomyocyte dedifferentiation were elevated in Ogt-deficient cardiomyocytes. Although no significant differences in cardiac dysfunction were apparent after recombination, it is possible that such changes in dedifferentiation markers could reflect a larger phenotypic shift within the Ogt-deficient cardiomyocytes. We conclude that cardiomyocyte Ogt is not required for cardiomyocyte hypertrophy in vivo; however, loss of Ogt may exert subtle phenotypic differences in cardiomyocytes that sensitize the heart to pressure overload-induced ventricular dysfunction.

Increased risk of volume overload with plasma compared with four‐factor prothrombin complex concentrate for urgent vitamin K antagonist reversal

PubMed Central

Refaai, Majed A.; Goldstein, Joshua N.; Lee, Martin L.; Durn, Billie L.; Milling, Truman J.; Sarode, Ravi

2015-01-01

BACKGROUND Plasma is commonly used for vitamin K antagonist (VKA) reversal, but observational studies suggest that it is associated with transfusion‐related adverse reactions (e.g., volume overload). However, this issue has not previously been addressed in a randomized controlled trial (RCT). STUDY DESIGN AND METHODS Factors associated with volume overload were examined using data from two Phase IIIb RCTs comparing plasma with four‐factor prothrombin complex concentrate (4F‐PCC, Beriplex/Kcentra, CSL Behring) for urgent VKA reversal. VKA‐treated patients with major bleeding (NCT00708435) or requiring an urgent surgical or invasive procedure (NCT00803101) were randomly assigned (1:1) to receive either plasma or 4F‐PCC, concomitant with vitamin K. Adverse events (AEs) and serious AEs were prospectively captured up to Day 10 and 45, respectively. Volume overload predictors were evaluated on a univariate and multivariate basis. RESULTS A total of 388 patients (4F‐PCC, n = 191; plasma, n = 197) were enrolled. Volume overload occurred in 34 (9%) patients (4F‐PCC, n = 9; plasma, n = 25). In univariate analyses, use of plasma (vs. 4F‐PCC), use of nonstudy plasma and/or platelets, race, history of congestive heart failure (CHF), and history of renal disease were associated with volume overload. In multivariate analyses, use of plasma (vs. 4F‐PCC), history of CHF, and history of renal disease were independent volume overload predictors. In an additional analysis restricted to volume overload events recorded up to Day 7, only use of plasma (vs. 4F‐PCC) was an independent volume overload predictor. CONCLUSIONS After adjusting for other potential risk factors, plasma use was independently associated with a greater risk of volume overload than 4F‐PCC in patients requiring urgent VKA reversal. PMID:26135740

Striking volume intolerance is induced by mimicking arterial baroreflex failure in normal left ventricular function.

PubMed

Funakoshi, Kouta; Hosokawa, Kazuya; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

2014-01-01

Patients with heart failure and preserved ejection fraction (HFpEF) are supersensitive to volume overload, and a striking increase in left atrial pressure (LAP) often occurs transiently and is rapidly resolved by intravascular volume reduction. The arterial baroreflex is a powerful regulator of intravascular stressed blood volume. We examined whether arterial baroreflex failure (FAIL) mimicked by constant carotid sinus pressure (CSP) causes a striking increase in LAP and systemic arterial pressure (AP) by volume loading in rats with normal left ventricular (LV) function. In anesthetized Sprague-Dawley rats, we isolated bilateral carotid sinuses and controlled CSP by a servo-controlled piston pump. We mimicked the normal arterial baroreflex by matching CSP to instantaneous AP and FAIL by maintaining CSP at a constant value regardless of AP. We infused dextran stepwise (infused volume [Vi]) until LAP reached 15 mm Hg and obtained the LAP-Vi relationship. We estimated the critical Vi as the Vi at which LAP reached 20 mm Hg. In FAIL, critical Vi decreased markedly from 19.4 ± 1.6 mL/kg to 15.6 ± 1.6 mL/kg (P < .01), whereas AP at the critical Vi increased (194 ± 6 mm Hg vs 163 ± 6 mm Hg; P < .01). We demonstrated that an artificial arterial baroreflex system we recently developed could fully restore the physiologic volume intolerance in the absence of native arterial baroreflex. Arterial baroreflex failure induces striking volume intolerance in the absence of LV dysfunction and may play an important role in the pathogenesis of acute heart failure, especially in states of HFpEF. Copyright © 2014 Elsevier Inc. All rights reserved.

B-type natriuretic peptide testing for detection of heart failure.

PubMed

Saul, Lauren; Shatzer, Melanie

2003-01-01

The incidence of heart failure (HF) is on the increase with the aging population. Heart failure can manifest as either systolic or diastolic dysfunction. Systolic dysfunction causes impaired ventricular contractility with an ejection fraction of less than 45%. In contrast, diastolic dysfunction is evidenced by impaired ventricular relaxation and an ejection fraction greater than 45%. The diagnosis of HF is challenging with patients who present with acute dyspnea and a history of chronic obstructive pulmonary disease or pneumonia. The pathophysiology of HF and the resulting compensatory mechanisms involve a complex neuroendocrine response that includes a release of natriuretic peptides including B-type natriuretic peptides (BNPs). Elevation of BNP is in response to ventricular wall stress and volume overload from HF. BNP promotes natriuresis, diuresis, and vasodilitation and therefore counteracts some of the deleterious effects of the neuroendocrine response in HF Recently, a new laboratory test for BNP has been developed to assist in rapid identification of patients with HF. Research studies have shown that BNP testing assists in differentiating between cardiac and pulmonary causes of acute dyspnea and could be used to evaluate effectiveness of therapy and as a predictor for length of stay and readmission.

Predictors of Sudden Cardiac Death in Doberman Pinschers with Dilated Cardiomyopathy.

PubMed

Klüser, L; Holler, P J; Simak, J; Tater, G; Smets, P; Rügamer, D; Küchenhoff, H; Wess, G

2016-05-01

Doberman Pinschers with dilated cardiomyopathy (DCM) are at high risk of sudden cardiac death (SCD). Risk factors for SCD are poorly defined. To assess cardiac biomarkers, Holter-ECG, echocardiographic variables and canine characteristics in a group of Doberman Pinschers with DCM dying of SCD and in a DCM control group to identify factors predicting SCD. A longitudinal prospective study was performed in 95 Doberman Pinschers with DCM. Forty-one dogs died within 3 months after the last cardiac examination (SCD-group) and were compared to 54 Doberman Pinschers with DCM surviving 1 year after inclusion. Holter-ECG, echocardiography, measurement of N-terminal prohormone of brain-natriuretic peptide (NT-proBNP), and cardiac Troponin I (cTnI) concentrations were recorded for all dogs. Volume overload of the left ventricle (left ventricular end-diastolic volume (LVEDV/BSA) > 91.3 mL/m²) was the single best variable to predict SCD. The probability of SCD increases 8.5-fold (CI0.95  = 0.8-35.3) for every 50 mL/m²-unit increment in LVEDV/BSA. Ejection fraction (EF), left ventricular end-systolic volume (LVESV/BSA) and NT-proBNP were highly correlated with LVEDV/BSA (r = -0.63, 0.96, 0.86, respectively). Generated conditional inference trees (CTREEs) revealed that the presence of ventricular tachycardia (VT), increased concentration of cTnI, and the fastest rate (FR) of ventricular premature complexes (VPC) ≥260 beats per minute (bpm) are additional important variables to predict SCD. Conditional inference trees provided in this study might be useful for risk assessment of SCD in Doberman Pinschers with DCM. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Management of unstable arrhythmias in cardiogenic shock.

PubMed

Saidi, Abdulfattah; Akoum, Nazem; Bader, Feras

2011-08-01

Atrial and ventricular arrhythmias commonly arise in the setting of cardiogenic shock and often result in hemodynamic deterioration. Causative factors include myocardial ischemia, volume overload, and metabolic disturbances. Correcting these factors plays an important role in managing arrhythmias in this setting. Ventricular arrhythmias are more ominous compared to atrial arrhythmias but both require prompt intervention with electrical shock and anti-arrhythmic drug suppression. Coronary reperfusion is key to improving survival, including reducing the risk of sudden cardiac arrest, in acute myocardial infarction. Case series have also demonstrated the value of intra-aortic balloon pump counter-pulsation in suppressing ventricular arrhythmias in cardiogenic shock. The mechanism of arrhythmia suppression may be due to improved coronary perfusion and afterload reduction. Percutaneous ventricular assist device placement may be effective in this setting; however, data addressing this specific endpoint are lacking. Anti-arrhythmic drug options for ventricular and atrial arrhythmia suppression, in the setting of cardiogenic shock, are relatively limited. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone. The other Class III agents, sotalol and dronedarone, are excluded due to associated mortality observed in the SWORD and ANDROMEDA trials, respectively. Dofetilide is renally excreted and causes QT interval prolongation. Care should be taken to avoid excessive drug accumulation due to poor kidney perfusion and function. Dofetilide is approved for use for atrial arrhythmias and has not been studied for ventricular arrhythmia suppression. The DIAMOND-CHF trial established its safety in the setting of heart failure. Amiodarone is very effective in suppressing both atrial and ventricular arrhythmias. It is often the drug of choice in heart failure. Its off-label use for atrial arrhythmias is very common. Care should be taken with intravenous amiodarone to avoid hypotension.

Fluid Volume Overload and Congestion in Heart Failure: Time to Reconsider Pathophysiology and How Volume Is Assessed.

PubMed

Miller, Wayne L

2016-08-01

Volume regulation, assessment, and management remain basic issues in patients with heart failure. The discussion presented here is directed at opening a reassessment of the pathophysiology of congestion in congestive heart failure and the methods by which we determine volume overload status. Peer-reviewed historical and contemporary literatures are reviewed. Volume overload and fluid congestion remain primary issues for patients with chronic heart failure. The pathophysiology is complex, and the simple concept of intravascular fluid accumulation is not adequate. The dynamics of interstitial and intravascular fluid compartment interactions and fluid redistribution from venous splanchnic beds to central pulmonary circulation need to be taken into account in strategies of volume management. Clinical bedside evaluations and right heart hemodynamic assessments can alert clinicians of changes in volume status, but only the quantitative measurement of total blood volume can help identify the heterogeneity in plasma volume and red blood cell mass that are features of volume overload in patients with chronic heart failure and help guide individualized, appropriate therapy-not all volume overload is the same. © 2016 American Heart Association, Inc.

Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function.

PubMed

Bermejo, Javier; Yotti, Raquel; Pérez del Villar, Candelas; del Álamo, Juan C; Rodríguez-Pérez, Daniel; Martínez-Legazpi, Pablo; Benito, Yolanda; Antoranz, J Carlos; Desco, M Mar; González-Mansilla, Ana; Barrio, Alicia; Elízaga, Jaime; Fernández-Avilés, Francisco

2013-08-15

In cardiovascular research, relaxation and stiffness are calculated from pressure-volume (PV) curves by separately fitting the data during the isovolumic and end-diastolic phases (end-diastolic PV relationship), respectively. This method is limited because it assumes uncoupled active and passive properties during these phases, it penalizes statistical power, and it cannot account for elastic restoring forces. We aimed to improve this analysis by implementing a method based on global optimization of all PV diastolic data. In 1,000 Monte Carlo experiments, the optimization algorithm recovered entered parameters of diastolic properties below and above the equilibrium volume (intraclass correlation coefficients = 0.99). Inotropic modulation experiments in 26 pigs modified passive pressure generated by restoring forces due to changes in the operative and/or equilibrium volumes. Volume overload and coronary microembolization caused incomplete relaxation at end diastole (active pressure > 0.5 mmHg), rendering the end-diastolic PV relationship method ill-posed. In 28 patients undergoing PV cardiac catheterization, the new algorithm reduced the confidence intervals of stiffness parameters by one-fifth. The Jacobian matrix allowed visualizing the contribution of each property to instantaneous diastolic pressure on a per-patient basis. The algorithm allowed estimating stiffness from single-beat PV data (derivative of left ventricular pressure with respect to volume at end-diastolic volume intraclass correlation coefficient = 0.65, error = 0.07 ± 0.24 mmHg/ml). Thus, in clinical and preclinical research, global optimization algorithms provide the most complete, accurate, and reproducible assessment of global left ventricular diastolic chamber properties from PV data. Using global optimization, we were able to fully uncouple relaxation and passive PV curves for the first time in the intact heart.

Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

PubMed

Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

2015-09-01

The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and magnitude of the stimuli, may play a role in the development of an adaptive or maladaptive phenotype. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

The Role of Cardiovascular Magnetic Resonance Imaging in Heart Failure.

PubMed

Peterzan, Mark A; Rider, Oliver J; Anderson, Lisa J

2016-11-01

Cardiovascular imaging is key for the assessment of patients with heart failure. Today, cardiovascular magnetic resonance imaging plays an established role in the assessment of patients with suspected and confirmed heart failure syndromes, in particular identifying aetiology. Its role in informing prognosis and guiding decisions around therapy are evolving. Key strengths include its accuracy; reproducibility; unrestricted field of view; lack of radiation; multiple abilities to characterise myocardial tissue, thrombus and scar; as well as unparalleled assessment of left and right ventricular volumes. T2* has an established role in the assessment and follow-up of iron overload cardiomyopathy and a role for T1 in specific therapies for cardiac amyloid and Anderson-Fabry disease is emerging.

Gender differences in left ventricular function in patients with isolated aortic stenosis.

PubMed

Favero, Luca; Giordan, Massimo; Tarantini, Giuseppe; Ramondo, Angelo Bruno; Cardaioli, Paolo; Isabella, Giambattista; Chioin, Raffaello; Lupia, Mario; Razzolini, Renato

2003-05-01

Hypertrophic response of the left ventricle to systolic overload in aortic stenosis appears to be gender-dependent. To examine gender-related differences in left ventricular (LV) function in patients with isolated severe aortic stenosis, 145 patients (65 women, 80 men; mean age 66 +/- 8 years; range: 50 to 89 years) with aortic valve area <0.8 cm2 who underwent cardiac catheterization were studied. No patient had associated myocardial, coronary or other valve disease; patients with diabetes mellitus and systemic hypertension were excluded. No significant differences were seen in aortic valve area between men and women. Neither were there any significant gender-related differences in LV end-systolic and end-diastolic volumes, LV end-diastolic pressure, LV mass indexed by body surface area, LV mass:volume ratio, LV mass:height ratio, elastic stiffness constant, ejection fraction, pulmonary wedge pressure, pulmonary arteriolar resistance and preload. Women showed significantly higher mean transaortic gradient, LV peak systolic pressure and peak systolic stress, end-systolic stress:end-systolic volume ratio, heart rate and cardiac index. In the subgroup of patients with LV pressure >199 mmHg, the mass:volume ratio was increased in men compared with women; of note, the mass:volume ratio in women was not increased in this subgroup compared with the general population. LV pump function in this subgroup was normal and did not differ between men and women. Although no clear-cut difference in hemodynamic parameters was seen, there was a trend towards a less compensatory increase in LV mass in females.

Endoplasmic reticulum stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) protects against pressure overload-induced heart failure and lung remodeling.

PubMed

Liu, Xiaoyu; Kwak, Dongmin; Lu, Zhongbing; Xu, Xin; Fassett, John; Wang, Huan; Wei, Yidong; Cavener, Douglas R; Hu, Xinli; Hall, Jennifer; Bache, Robert J; Chen, Yingjie

2014-10-01

Studies have reported that development of congestive heart failure is associated with increased endoplasmic reticulum stress. Double stranded RNA-activated protein kinase R-like endoplasmic reticulum kinase (PERK) is a major transducer of the endoplasmic reticulum stress response and directly phosphorylates eukaryotic initiation factor 2α, resulting in translational attenuation. However, the physiological effect of PERK on congestive heart failure development is unknown. To study the effect of PERK on ventricular structure and function, we generated inducible cardiac-specific PERK knockout mice. Under unstressed conditions, cardiac PERK knockout had no effect on left ventricular mass, or its ratio to body weight, cardiomyocyte size, fibrosis, or left ventricular function. However, in response to chronic transverse aortic constriction, PERK knockout mice exhibited decreased ejection fraction, increased left ventricular fibrosis, enhanced cardiomyocyte apoptosis, and exacerbated lung remodeling in comparison with wild-type mice. PERK knockout also dramatically attenuated cardiac sarcoplasmic reticulum Ca(2+)-ATPase expression in response to aortic constriction. Our findings suggest that PERK is required to protect the heart from pressure overload-induced congestive heart failure. © 2014 American Heart Association, Inc.

Multiple left anterior descending coronary artery to left ventricular fistula - A case series and literature review.

PubMed

Iyer, Praneet; Yelisetti, Rishitha

2017-10-01

Coronary artery fistulas (CAFs) are found in 0.3-0.8% of patients who undergo coronary angiography. CAFs are defined as single or multiple, small or large direct communications that arise from one or more coronary arteries and enter into one of the four cardiac chambers or major vessels. We present two cases of multiple coronary artery fistulas arising from diagonal and left anterior descending (LAD) branches of left coronary artery draining into the left ventricle. In both the cases, No intervention was performed. Of the congenital fistulas, two major groups are identified: solitary CAFs or coronary artery-left ventricular multiple micro-fistulas (CALVMMFs). Noninvasive techniques such as transthoracic echocardiography, transesophageal echocardiography and magnetic resonance imaging are becoming increasingly popular for diagnosis and follow-up of CAFs. Despite the advent of these newer non-invasive modalities, coronary angiography remains the gold standard for diagnosis. Treatment of CAFs is indicated when the patients are symptomatic with left ventricular volume overload, myocardial ischemia, left ventricular dysfunction or in the presence of a large or increasing left-to-right shunt. If the fistula is small and hemodynamically insignificant, it can be managed with conservative management. Multiple left anterior descending to left ventricle (LV) fistulas are extremely rare and, as per our literature review, we noted only a few case reports of coronary artery fistulas between branches of LAD and left ventricle.

Bi-ventricular finite element model of right ventricle overload in the healthy rat heart.

PubMed

Masithulela, Fulufhelo

2016-11-25

The recognition of RV overpressure is critical to human life, as this may signify morbidity and mortality. Right ventricle (RV) dysfunction is understood to have an impact on the performance of the left ventricle (LV), but the mechanisms remain poorly understood. It is understood that ventricular compliance has the ability to affect cardiac performance. In this study, a bi-ventricular model of the rat heart was used in preference to other, single-ventricle models. Finite element analysis (FEA) of the bi-ventricular model provides important information on the function of the healthy heart. The passive myocardium was modelled as a nearly incompressible, hyperelastic, transversely isotropic material using finite element (FE) methods. Bi-ventricular geometries of healthy rat hearts reconstructed from magnetic resonance images were imported in Abaqus©. In simulating the normal passive filling of the rat heart, pressures of 4.8 kPa and 0.0098 kPa were applied to the inner walls of the LV and RV respectively. In addition, to simulate the overpressure of the RV, pressures of 2.4 kPa and 4.8 kPa were applied to the endocardial walls of the LV and RV respectively. As boundary conditions, the circumferential and longitudinal displacements at the base were set to zero. The radial displacements at the base were left free. The results show that the average circumferential stress at the mid-wall in the overloaded model increased from 2.8 kPa to 18.2 kPa. The average longitudinal stress increased from 1.5 kPa to 9.7 kPa. Additionally, in the radial direction, the average stress increased from 0.1 kPa to 0.6 kPa in the mid-wall. The average circumferential strain was found to be 0.138 and 0.100 on the endocardium of the over pressured and healthy model respectively. The average circumferential stress at the epicardium, mid-wall and endocardium in the case of a normal heart is 10 times lower than in the overloaded heart model. The finite analysis method is able to provide insights into the behaviour of the over pressured model (myocardium). In the overloaded model the high stresses and strains were observed on the septal wall. The bi-ventricular model was shown to provide useful information relating to the over pressured ventricle. The possible heart dysfunction may be attributable to high stress and strain in the over pressured heart.

Diverse molecular forms of plasma B-type natriuretic peptide in heart failure.

PubMed

Nishikimi, Toshio; Minamino, Naoto; Nakao, Kazuwa

2011-06-01

Recent studies have shown that not only plasma B-type natriuretic peptide (BNP)-32, but also plasma proBNP-108 is increased in heart failure (HF), and that the current BNP-32 assay kit crossreacts with proBNP-108. It also was shown that both BNP-32 and proBNP-108 were higher in HF than in normal. The proBNP-108/total BNP (BNP-32 + proBNP-108) ratio was widely distributed and patients with HF with ventricular overload had higher proBNP-108/total BNP ratio than HF patients with atrial overload. Consistent with this finding, proBNP-108 was the major molecular form in ventricular tissue, and BNP-32 was the major molecular form in atrial tissue. In addition, proBNP-108 was the major molecular form of BNP in pericardial fluid. The proBNP-108/total BNP ratio increased with deterioration of HF and decreased with improvement of HF. Thus, not only BNP-32, but also proBNP-108 is increased in HF and the proBNP-108/total BNP ratio also rises in association with pathophysiological conditions such as ventricular overload. A new hypothesis that O-glycosylation at Thr71 in a region close to the cleavage site impairs proBNP-108 processing was proposed. In the future, the precise mechanism of increased proBNP-108 in HF should be elucidated.

Xanthine Oxidase Inhibition with Febuxostat Attenuates Systolic Overload-induced Left Ventricular Hypertrophy and Dysfunction in Mice

PubMed Central

Xu, Xin; Hu, Xinli; Lu, Zhongbing; Zhang, Ping; Zhao, Lin; Wessale, Jerry L.; Bache, Robert J.; Chen, Yingjie

2008-01-01

The purine analog xanthine oxidase (XO) inhibitors (XOIs), allopurinol and oxypurinol, have been reported to protect against heart failure secondary to myocardial infarction or rapid ventricular pacing. Since these agents might influence other aspects of purine metabolism that could influence their effect, this study examined the effect of the non-purine XOI, febuxostat, on pressure overload-induced left ventricular (LV) hypertrophy and dysfunction. Transverse aortic constriction (TAC) in mice caused LV hypertrophy and dysfunction as well as increased myocardial nitrotyrosine at 8 days. TAC also caused increased phosphorylated Akt (p-AktSer473), p42/44 extracellular signal-regulated kinase (p-ErkThr202/Tyr204) and mammalian target of rapamycin (mTOR) (p-mTORSer2488). XO inhibition with febuxostat (5mg/kg/day by gavage for 8 days) beginning ~60 minutes after TAC attenuated the TAC-induced LV hypertrophy and dysfunction. Febuxostat blunted the TAC-induced increases in nitrotyrosine (indicating reduced myocardial oxidative stress), p-ErkThr202/Tyr204 and p-mTORSer2488, with no effect on total Erk or total mTOR. Febuxostat had no effect on myocardial p-AktSer473 or total Akt. The results suggest that XO inhibition with febuxostat reduced oxidative stress in the pressure overloaded LV, thereby diminishing the activation of pathways that result in pathologic hypertrophy and contractile dysfunction. PMID:18995179

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PubMed

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Aldosterone and mortality in hemodialysis patients: role of volume overload.

PubMed

Hung, Szu-Chun; Lin, Yao-Ping; Huang, Hsin-Lei; Pu, Hsiao-Fung; Tarng, Der-Cherng

2013-01-01

Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality. We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance). Baseline plasma aldosterone was measured before dialysis and categorized as low (<140 pg/mL), middle (140 to 280 pg/mL) and high (>280 pg/mL). Overall, 36% (n = 119) of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78) in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69-3.75) and first cardiovascular event (2.01; 95% confidence interval, 1.28-4.15) in the absence of volume overload. The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.

Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

PubMed

Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

2008-12-01

To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Serum levels of natriuretic peptides in children with various types of loading conditions.

PubMed

Eerola, Anneli; Jokinen, Eero; Pihkala, Jaana I

2009-06-01

To evaluate the influence of volume overload of the left (LV) and right ventricle (RV) and pressure overload of LV and restrictive physiology on levels of N-terminal proatriopeptide (ANPN) and N-terminal pro-brain natriuretic peptide (NT-proBNP). We studied 41 children with atrial septal defect (ASD), 35 with patent ductus arteriosus (PDA), 27 with coarctation of the aorta (CoA), 25 with restrictive physiology caused by Mulibrey nanism, and 64 control children. We measured serum concentrations of natriuretic peptides and evaluated ventricular size and function with echocardiography. In patients with ASD, PDA, and Mulibrey nanism, levels of both ANPN and NT-proBNP were higher than in controls but in children with CoA, only ANPN levels were higher. ANPN levels correlated with RV size in ASD and NT-proBNP levels with LV size in PDA. In patients with restriction, NT-proBNP levels correlated negatively with LV size. Correlation between echo measurements and levels of natriuretic peptides varied according to loading condition. Measurement of natriuretic peptide levels provides a supplemental method for non-invasive haemodynamic evaluation of children's heart disease.

Atrioventricular valve repair in patients with single-ventricle physiology: mechanisms, techniques of repair, and clinical outcomes.

PubMed

Honjo, Osami; Mertens, Luc; Van Arsdell, Glen S

2011-01-01

Significant atrioventricular (AV) valve insufficiency in patient with single ventricle-physiology is strongly associated with poor survival. Herein we discuss the etiology and mechanism of development of significant AV valve insufficiency in patients with single-ventricle physiology, surgical indication and repair techniques, and clinical outcomes along with our 10-year surgical experience. Our recent clinical series and literature review indicate that it is of prime importance to appreciate the high incidence and clinical effect of the structural abnormalities of AV valve. Valve repair at stage II palliation may minimize the period of volume overload, thereby potentially preserving post-repair ventricular function. Since 85% of the AV valve insufficiency was associated with structural abnormalities, inspection of an AV valve that has more than mild to moderate insufficiency is recommended because they are not likely to be successfully treated with volume unloading surgery alone. Copyright © 2011 Elsevier Inc. All rights reserved.

The efficacy and tolerability of azilsartan in obese insulin-resistant mice with left ventricular pressure overload.

PubMed

Tarikuz Zaman, A K M; McLean, Danielle L; Sobel, Burton E

2013-10-01

Angiotensin II receptor blockers (ARBs) are used widely for the treatment of heart failure. However, their use in obese and insulin-resistant patients remains controversial. To clarify their potential efficacy in these conditions, we administered azilsartan medoxomil (azilsartan), a prodrug of an angiotensin II receptor blocker to mice fed a high-fat diet (HFD) with left ventricular (LV) pressure overload (aortic banding). LV fibrosis (hydroxyproline), cardiac plasminogen activator inhibitor-1 (PAI-1; a marker of profibrosis), and creatine kinase (a marker of myocardial viability and energetics) were assessed. LV wall thickness and cardiac function were assessed echocardiographically. Mice given a HFD were obese and insulin resistant. Their LV hypertrophy was accompanied by greater LV PAI-1 and reduced LV creatine kinase compared with normal diet controls. Drug treatment reduced LV wall thickness, hypertrophy, and PAI-1 and increased cardiac output after aortic banding compared with results in HFD vehicle controls. Thus, azilsartan exerted favorable biological effects on the hearts of obese insulin-resistant mice subjected to LV pressure overload consistent with its potential utility in patients with analogous conditions.

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.

Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading

NASA Technical Reports Server (NTRS)

Tagawa, H.; Koide, M.; Sato, H.; Zile, M. R.; Carabello, B. A.; Cooper, G. 4th

1998-01-01

Increased microtubule density causes cardiocyte contractile dysfunction in right ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and contractile abnormalities persist and progress during the transition to failure. Although more severe in cells from failing than hypertrophied RVs, the mechanical defects are normalized in each case by microtubule depolymerization. To define the role of increased microtubule density in left ventricular (LV) pressure-overload hypertrophy and failure, in a given LV we examined ventricular mechanics, sarcomere mechanics, and free tubulin and microtubule levels in control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and with initially compensated hypertrophy that had progressed to LV muscle failure. In comparing initial values with those at study 8 weeks later, dogs with hypertrophy alone had a very substantial increase in LV mass but preservation of a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy and associated failure had a substantial but lesser increase in LV mass and a reduction in ejection fraction, as well as a marked increase in mean systolic wall stress. Cardiocyte contractile function was equivalent, and unaffected by microtubule depolymerization, in cells from control LVs and those with compensated hypertrophy. In contrast, cardiocyte contractile function in cells from failing LVs was quite depressed but was normalized by microtubule depolymerization. Microtubules were increased only in failing LVs. These contractile and cytoskeletal changes, when assayed longitudinally in a given dog by biopsy, appeared in failing ventricles only when wall stress began to increase and function began to decrease. Thus, the microtubule-based cardiocyte contractile dysfunction characteristic of pressure-hypertrophied myocardium, originally described in the RV, obtains equally in the LV but is shown here to have a specific association with increased wall stress.

Characteristics of single Ca(2+) channel kinetics in feline hypertrophied ventricular myocytes.

PubMed

Yang, Xiangjun; Hui, Jie; Jiang, Tingbo; Song, Jianping; Liu, Zhihua; Jiang, Wenping

2002-04-01

To explore the mechanism underlying the prolongation of action potential and delayed inactivation of the L-type Ca(2+) (I(Ca, L)) current in a feline model of left ventricular system hypertension and concomitant hypertrophy. Single Ca(2+) channel properties in myocytes isolated from normal and pressure overloaded cat left ventricles were studied, using patch-clamp techniques. Left ventricular pressure overload was induced by partial ligation of the ascending aorta for 4 - 6 weeks. The amplitude of single Ca(2+) channel current evoked by depolarizing pulses from -40 mV to 0 mV was 1.02 +/- 0.03 pA in normal cells and 1.05 +/- 0.03 pA in hypertrophied cells, and there was no difference in single channel current-voltage relationships between the groups since slope conductance was 26.2 +/- 1.0 pS in normal and hypertrophied cells, respectively. Peak amplitudes of the ensemble-averaged single Ca(2+) channel currents were not different between the two groups of cells. However, the amplitude of this averaged current at the end of the clamp pulse was significantly larger in hypertrophied cells than in normal cells. Open-time histograms revealed that open-time distribution was fitted by a single exponential function in channels of normal cells and by a two exponential function in channels of hypertrophied cells. The number of long-lasting openings was increased in channels of hypertrophied cells, and therefore the calculated mean open time of the channel was significantly longer compared to normal controls. Kinetic changes in the Ca(2+) channel may underlie both hypertrophy-associated delayed inactivation of the Ca(2+) current and, in part, the pressure overload-induced action potential lengthening in this cat model of ventricular left systolic hypertension and hypertrophy.

Sildenafil ameliorates right ventricular early molecular derangement during left ventricular pressure overload.

PubMed

Imai, Yousuke; Kariya, Taro; Iwakiri, Masaki; Yamada, Yoshitsugu; Takimoto, Eiki

2018-01-01

Right ventricular (RV) dysfunction following left ventricular (LV) failure is associated with poor prognosis. RV remodeling is thought initiated by the increase in the afterload of RV due to secondary pulmonary hypertension (PH) to impaired LV function; however, RV molecular changes might occur in earlier stages of the disease. cGMP (cyclic guanosine monophosphate)-phosphodiesterase 5 (PDE5) inhibitors, widely used to treat PH through their pulmonary vasorelaxation properties, have shown direct cardiac benefits, but their impacts on the RV in LV diseases are not fully determined. Here we show that RV molecular alterations occur early in the absence of RV hemodynamic changes during LV pressure-overload and are ameliorated by PDE5 inhibition. Two-day moderate LV pressure-overload (transverse aortic constriction) neither altered RV pressure/ function nor RV weight in mice, while it induced only mild LV hypertrophy. Importantly, pathological molecular features were already induced in the RV free wall myocardium, including up-regulation of gene markers for hypertrophy and inflammation, and activation of extracellular signal-regulated kinase (ERK) and calcineurin. Concomitant PDE5 inhibition (sildenafil) prevented induction of such pathological genes and activation of ERK and calcineurin in the RV as well as in the LV. Importantly, dexamethasone also prevented these RV molecular changes, similarly to sildenafil treatment. These results suggest the contributory role of inflammation to the early pathological interventricular interaction between RV and LV. The current study provides the first evidence for the novel early molecular cross-talk between RV and LV, preceding RV hemodynamic changes in LV disease, and supports the therapeutic strategy of enhancing cGMP signaling pathway to treat heart diseases.

Heart Failure Is Common and Under-Recognized in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia.

PubMed

Gilotra, Nisha A; Bhonsale, Aditya; James, Cynthia A; Te Riele, Anneline S J; Murray, Brittney; Tichnell, Crystal; Sawant, Abhishek; Ong, Chin Siang; Judge, Daniel P; Russell, Stuart D; Calkins, Hugh; Tedford, Ryan J

2017-09-01

Heart failure (HF) prevalence in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) varies depending on study cohort and is not well characterized. This study sought to determine prevalence and predictors of HF in ARVC/D. Clinical HF, defined as at least 1 HF sign or symptom, was retrospectively adjudicated for 289 patients meeting ARVC/D Task Force Criteria. HF was present in 142 patients (49%): 113 had isolated RV involvement and 29 had evidence of LV dysfunction. Average age of HF onset was 40±14 years. Most commonly reported symptoms were exertional dyspnea (78%) and fatigue (73%). Only 40% (n=57/142) had signs of volume overload. Left-sided HF signs were rare. Patients with clinical HF before ARVC/D diagnosis (n=31) were older ( P =0.005) and met fewer Task Force Criteria ( P =0.013) than those who developed HF after ARVC/D presentation. Female sex (odds ratio, 2.2; 95% confidence interval, 1.21-4.01; P =0.01) and lateral precordial T-wave inversions (odds ratio, 9.87; 95% confidence interval, 1.07-91.1; P =0.043) were associated with increased odds of HF. Additionally, patients with symptomatic LV dysfunction had higher odds of lateral precordial T-wave inversions (odds ratio, 18.4; 95% confidence interval, 2.92-116.18; P =0.002). Patients with HF were more likely to undergo heart transplantation (15/142 versus 1/147; P <0.001) or die during study follow-up period (7 versus 0; P =0.007). HF symptoms, especially exertional dyspnea, are common in ARVC/D; yet, classic left-sided signs are typically absent and less than half have evidence of volume overload. Given the unique predominately right-sided phenotype, a large portion of patients with HF may be under-recognized. © 2017 American Heart Association, Inc.

Chronic high-fat diet-induced obesity decreased survival and increased hypertrophy of rats with experimental eccentric hypertrophy from chronic aortic regurgitation.

PubMed

Dhahri, Wahiba; Drolet, Marie-Claude; Roussel, Elise; Couet, Jacques; Arsenault, Marie

2014-09-24

The composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival. Male Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later. As expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet. HF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.

Left atrial volume is not an index of left ventricular diastolic dysfunction in patients with sickle cell anaemia.

PubMed

Hammoudi, Nadjib; Charbonnier, Magali; Levy, Pierre; Djebbar, Morad; Stankovic Stojanovic, Katia; Ederhy, Stéphane; Girot, Robert; Cohen, Ariel; Isnard, Richard; Lionnet, François

2015-03-01

Left ventricular diastolic dysfunction (LVDD) is common in sickle cell anaemia (SCA). Left atrial (LA) size is widely used as an index of LVDD; however, LA enlargement in SCA might also be due to chronic volume overload. To investigate whether LA size can be used to diagnose LVDD in SCA. One hundred and twenty-seven adults with stable SCA underwent echocardiographic assessment. LA volume was measured by the area-length method and indexed to body surface area (LAVi). Left ventricular (LV) filling pressures were assessed using the ratio of early peak diastolic velocities of mitral inflow and septal annular mitral plane (E/e'). Using mitral inflow profile and E/e', LV diastolic function was classified as normal or abnormal. LAVi>28mL/m(2) was used as the threshold to define LA enlargement. The mean age was 28.6±8.5years; there were 83 women. Mean LAVi was 48.3±11.1mL/m(2) and 124 (98%) patients had LA dilatation. In multivariable analysis, age, haemoglobin concentration and LV end-diastolic volume index were independent determinants of LAVi (R(2)=0.51; P<0.0001). E/e' was not linked to LAVi (P=0.43). Twenty patients had LVDD; when compared with patients without LVDD, they had a similar LAVi (52.2±14.7 and 47.5±10.2mL/m(2), respectively; P=0.29). Receiver operating characteristics curve analysis showed that LAVi could not be used to diagnose LVDD (area under curve=0.58; P=0.36). LA enlargement is common in SCA but appears not to be linked to LVDD. LAVi in this population is related to age, haemoglobin concentration and LV morphology. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Assessment and Management of Volume Overload and Congestion in Chronic Heart Failure: Can Measuring Blood Volume Provide New Insights?

PubMed

Miller, Wayne L

2017-01-01

Volume overload and fluid congestion remain primary clinical challenges in the assessment and management of patients with chronic heart failure (HF). The pathophysiology of volume regulation is complex, and the simple concept of passive intravascular fluid accumulation is not adequate. The dynamics of interstitial and intravascular fluid compartment interactions and fluid redistribution from venous splanchnic beds to the central pulmonary circulation need to be taken into account in strategies of volume management. Clinical bedside evaluations and right heart hemodynamic assessments can alert of changes in volume status, but only the quantitative measurement of total blood volume can help identify the heterogeneity in plasma volume and red blood cell mass that are features of volume overload in chronic HF. The quantitative assessment of intravascular volume is an effective tool to help guide individualized, appropriate therapy. Not all volume overload is the same, and the measurement of intravascular volume identifies heterogeneity to guide tailored therapy.

Left ventricular outflow tract mean systolic acceleration as a surrogate for the slope of the left ventricular end-systolic pressure-volume relationship

NASA Technical Reports Server (NTRS)

Bauer, Fabrice; Jones, Michael; Shiota, Takahiro; Firstenberg, Michael S.; Qin, Jian Xin; Tsujino, Hiroyuki; Kim, Yong Jin; Sitges, Marta; Cardon, Lisa A.; Zetts, Arthur D.;

The use of renal replacement therapy in acute decompensated heart failure.

PubMed

Udani, Suneel M; Murray, Patrick T

2009-01-01

The worsening of renal function in the context of decompensated heart failure is an increasingly common clinical scenario, dubbed the cardiorenal syndrome. Its development is not completely understood; however, it results from the hemodynamic and neurohumoral alterations that occur in the setting of left ventricular pressure and volume overload with poor cardiac output. Diuretics have been the mainstay of treatment; however, they are often unsuccessful in reversing the vicious cycle of volume overload, worsening cardiac function, and azotemia. Renal replacement therapy (RRT) in the form of isolated or continuous ultrafiltration (UF) with or without a component of solute clearance (hemofiltration or hemodialysis) has been increasingly utilized as a therapeutic tool in this setting. Initial clinical trial data on the use of UF have demonstrated promising cardiac outcomes with regard to fluid removal and symptom relief without worsening renal function. The addition of a component of solute clearance may provide additional benefits in these patients with varying degrees of renal impairment. The exact clinical setting in which the various forms of RRT should be applied as initial or early therapy for acute decompensated heart failure (ADHF) remains unknown. More research examining the use of RRT in ADHF is necessary; however, it appears that the patients with the most severe clinical presentations have the best chance of benefiting from the early application of RRT.

Power of resting echocardiographic measurements to classify pulmonary hypertension patients according to European society of cardiology exercise testing risk stratification cut-offs.

PubMed

Rehman, Michaela B; Garcia, Rodrigue; Christiaens, Luc; Larrieu-Ardilouze, Elisa; Howard, Luke S; Nihoyannopoulos, Petros

2018-04-15

Right ventricular function is the major determinant of morbidity and mortality in pulmonary arterial hypertension (PAH). The ESC risk assessment strategy for PAH is based on clinical status, exercise testing, NTproBNP, imaging and haemodynamics but does not include right ventricular function. Our aims were to test the power of resting echocardiographic measurements to classify PAH patients according to ESC exercise testing risk stratification cut-offs and to determine if the classification power of echocardiographic parameters varied in chronic thrombo-embolic pulmonary hypertension (CTEPH). We prospectively and consecutively recruited 46 PAH patients and 42 CTEPH patients referred for cardio-pulmonary exercise testing and comprehensive transthoracic echocardiography. Exercise testing parameters analyzed were peak oxygen consumption, percentage of predicted maximal oxygen consumption and the slope of ventilation against carbon dioxide production. Receiver operator characteristic curves were used to determine the optimal diagnostic cut-off values of echocardiographic parameters for classifying the patients in intermediate or high risk category according to exercise testing. Measurements of right ventricular systolic function were the best for classifying in PAH (area under the curve 0.815 to 0.935). Measurements of right ventricular pressure overload (0.810 to 0.909) were optimal for classifying according to exercise testing in CTEPH. Measurements of left ventricular function were of no use in either group. Measurements of right ventricular systolic function can classify according to exercise testing risk stratification cut-offs in PAH. However, this is not the case in CTEPH where pressure overload, rather than right ventricular function seems to be linked to exercise performance. Copyright © 2018 Elsevier B.V. All rights reserved.

Attenuated hypertrophic response to pressure overload in a lamin A/C haploinsufficiency mouse.

PubMed

Cupesi, Mihaela; Yoshioka, Jun; Gannon, Joseph; Kudinova, Anastacia; Stewart, Colin L; Lammerding, Jan

2010-06-01

Inherited mutations cause approximately 30% of all dilated cardiomyopathy cases, with autosomal dominant mutations in the LMNA gene accounting for more than one third of these. The LMNA gene encodes the nuclear envelope proteins lamins A and C, which provide structural support to the nucleus and also play critical roles in transcriptional regulation. Functional deletion of a single allele is sufficient to trigger dilated cardiomyopathy in humans and mice. However, whereas Lmna(-/-) mice develop severe muscular dystrophy and dilated cardiomyopathy and die by 8 weeks of age, heterozygous Lmna(+/-) mice have a much milder phenotype, with changes in ventricular function and morphology only becoming apparent at 1 year of age. Here, we studied 8- to 20-week-old Lmna(+/-) mice and wild-type littermates in a pressure overload model to examine whether increased mechanical load can accelerate or exacerbate myocardial dysfunction in the heterozygotes. While overall survival was similar between genotypes, Lmna(+/-) animals had a significantly attenuated hypertrophic response to pressure overload as evidenced by reduced ventricular mass and myocyte size. Analysis of pressure overload-induced transcriptional changes suggested that the reduced hypertrophy in the Lmna(+/-) mice was accompanied by impaired activation of the mechanosensitive gene Egr-1. In conclusion, our findings provide further support for a critical role of lamins A and C in regulating the cellular response to mechanical stress in cardiomyocytes and demonstrate that haploinsufficiency of lamins A and C alone is sufficient to alter hypertrophic responses and cardiac function in the face of pressure overload in the heart. (c) 2009 Elsevier Ltd. All rights reserved.

Attenuated hypertrophic response to pressure overload in a lamin A/C haploinsufficiency mouse

PubMed Central

Cupesi, Mihaela; Yoshioka, Jun; Gannon, Joseph; Kudinova, Anastacia; Stewart, Colin L.; Lammerding, Jan

2009-01-01

Inherited mutations cause approximately 30% of all dilated cardiomyopathy cases, with autosomal dominant mutations in the LMNA gene accounting for more than one third of these. The LMNA gene encodes the nuclear envelope proteins lamins A and C, which provide structural support to the nucleus and also play critical roles in transcriptional regulation. Functional deletion of a single allele is sufficient to trigger dilated cardiomyopathy in humans and mice. However, whereas Lmna−/− mice develop severe muscular dystrophy and dilated cardiomyopathy and die by 8 weeks of age, heterozygous Lmna+/− mice have a much milder phenotype, with changes in ventricular function and morphology only becoming apparent at one year of age. Here, we studied 8 to 20 week old Lmna+/− mice and wild-type littermates in a pressure overload model to examine whether increased mechanical load can accelerate or exacerbate myocardial dysfunction in the heterozygotes. While overall survival was similar between genotypes, Lmna+/− animals had a significantly attenuated hypertrophic response to pressure overload as evidenced by reduced ventricular mass and myocyte size. Analysis of pressure-overload induced transcriptional changes suggested that the reduced hypertrophy in the Lmna+/− mice was accompanied by impaired activation of the mechanosensitive gene Egr-1. In conclusion, our findings provide further support for a critical role of lamins A and C in regulating the cellular response to mechanical stress in cardiomyocytes and demonstrate that haploinsufficiency of lamins A and C alone is sufficient to alter hypertrophic responses and cardiac function in the face of pressure overload in the heart. PMID:19913544

Changes in right ventricular function assessed by echocardiography in dog models of mild RV pressure overload.

PubMed

Morita, Tomoya; Nakamura, Kensuke; Osuga, Tatsuyuki; Yokoyama, Nozomu; Morishita, Keitaro; Sasaki, Noboru; Ohta, Hiroshi; Takiguchi, Mitsuyoshi

2017-07-01

The assessment of hemodynamic change by echocardiography is clinically useful in patients with pulmonary hypertension. Recently, mild elevation of the mean pulmonary arterial pressure (PAP) has been shown to be associated with increased mortality. However, changes in the echocardiographic indices of right ventricular (RV) function are still unknown. The objective of this study was to validate the relationship between echocardiographic indices of RV function and right heart catheterization variables under a mild RV pressure overload condition. Echocardiography and right heart catheterization were performed in dog models of mild RV pressure overload induced by thromboxane A 2 analog (U46619) (n=7). The mean PAP was mildly increased (19.3±1.1 mm Hg), and the cardiac index was decreased. Most echocardiographic indices of RV function were significantly impaired even under a mild RV pressure overload condition. Multivariate analysis revealed that the RV free wall longitudinal strain (RVLS), standard deviation of the time-to-peak longitudinal strain of RV six segments (RV-SD) by speckle-tracking echocardiography, and Tei index were independent echocardiographic predictors of the mean PAP (free wall RVLS, β=-0.60, P<.001; RV-SD, β=0.40, P=.011), pulmonary vascular resistance (free wall RVLS, β=-0.39, P=.020; RV-SD, β=0.47, P=.0086; Tei index, β=0.34, P=.047), and cardiac index (Tei index, β=-0.65, P<.001). Free wall RVLS, RV-SD, and Tei index are useful for assessing the hemodynamic change under a mild RV pressure overload condition. © 2017, Wiley Periodicals, Inc.

Global left atrial failure in heart failure.

PubMed

Triposkiadis, Filippos; Pieske, Burkert; Butler, Javed; Parissis, John; Giamouzis, Gregory; Skoularigis, John; Brutsaert, Dirk; Boudoulas, Harisios

2016-11-01

The left atrium plays an important role in the maintenance of cardiovascular and neurohumoral homeostasis in heart failure. However, with progressive left ventricular dysfunction, left atrial (LA) dilation and mechanical failure develop, which frequently culminate in atrial fibrillation. Moreover, LA mechanical failure is accompanied by LA endocrine failure [deficient atrial natriuretic peptide (ANP) processing-synthesis/development of ANP resistance) and LA regulatory failure (dominance of sympathetic nervous system excitatory mechanisms, excessive vasopressin release) contributing to neurohumoral overactivity, vasoconstriction, and volume overload (global LA failure). The purpose of the present review is to describe the characteristics and emphasize the clinical significance of global LA failure in patients with heart failure. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Congestive heart failure caused by transvenous pacemaker lead prolapse and associated right ventricular outflow tract obstruction in a dog.

PubMed

Djani, D M; Coleman, A E; Rapoport, G S; Schmiedt, C W; Layher, J; Thomason, J D

2016-12-01

A 16-year-old dog was presented for cough as well as increased respiratory rate and effort three years after implantation of a single-lead transvenous artificial pacemaker system. Thoracic radiographs and echocardiography disclosed prolapse of the pacemaker lead into the main pulmonary artery, causing severe pulmonary insufficiency and right-sided volume overload. Repositioning of the pacemaker lead led to improvement of pulmonary insufficiency and resolution of the dog's clinical signs and cavitary effusions. This case describes a late complication of pacemaker implantation that may be avoided by appropriate use of the manufacturer-provided anchoring sleeve and avoidance of excessive lead redundancy. Copyright © 2016 Elsevier B.V. All rights reserved.

The Role of Cardiovascular Magnetic Resonance Imaging in Heart Failure

PubMed Central

Peterzan, Mark A; Rider, Oliver J

2016-01-01

Cardiovascular imaging is key for the assessment of patients with heart failure. Today, cardiovascular magnetic resonance imaging plays an established role in the assessment of patients with suspected and confirmed heart failure syndromes, in particular identifying aetiology. Its role in informing prognosis and guiding decisions around therapy are evolving. Key strengths include its accuracy; reproducibility; unrestricted field of view; lack of radiation; multiple abilities to characterise myocardial tissue, thrombus and scar; as well as unparalleled assessment of left and right ventricular volumes. T2* has an established role in the assessment and follow-up of iron overload cardiomyopathy and a role for T1 in specific therapies for cardiac amyloid and Anderson–Fabry disease is emerging. PMID:28785465

Arrhythmogenic right ventricular cardiomyopathy mimics: role of cardiovascular magnetic resonance

PubMed Central

2013-01-01

Background Cardiovascular magnetic resonance (CMR) is commonly used in patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) based on ECG, echocardiogram and Holter. However, various diseases may present with clinical characteristics resembling ARVC causing diagnostic dilemmas. The aim of this study was to explore the role of CMR in the differential diagnosis of patients with suspected ARVC. Methods 657 CMR referrals suspicious for ARVC in a single tertiary referral centre were analysed. Standardized CMR imaging protocols for ARVC were performed. Potential ARVC mimics were grouped into: 1) displacement of the heart, 2) right ventricular overload, and 3) non ARVC-like cardiac scarring. For each, a judgment of clinical impact was made. Results Twenty patients (3.0%) fulfilled imaging ARVC criteria. Thirty (4.6%) had a potential ARVC mimic, of which 25 (3.8%) were considered clinically important: cardiac displacement (n=17), RV overload (n=7) and non-ARVC like myocardial scarring (n=4). One patient had two mimics; one patient had dual pathology with important mimic and ARVC. RV overload and scarring conditions were always thought clinically important whilst the importance of cardiac displacement depended on the degree of displacement from severe (partial absence of pericardium) to epiphenomenon (minor kyphoscoliosis). Conclusions Some patients referred for CMR with suspected ARVC fulfil ARVC imaging criteria (3%) but more have otherwise unrecognised diseases (4.6%) mimicking potentially ARVC. Clinical assessment should reflect this, emphasising the assessment and/or exclusion of potential mimics in parallel with the detection of ARVC major and minor criteria. PMID:23398958

Does oxidative stress modulate left ventricular diastolic function in asymptomatic subjects with hereditary hemochromatosis?

PubMed

Shizukuda, Yukitaka; Bolan, Charles D; Tripodi, Dorothy J; Sachdev, Vandana; Nguyen, Tammy T; Botello, Gilberto; Yau, Yu-Ying; Sidenko, Stanislav; Inez, Ernst; Ali, Mir I; Waclawiw, Myron A; Leitman, Susan F; Rosing, Douglas R

2009-11-01

Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography-derived measure of diastolic function, may detect such changes. we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Ninety-four consecutive visits of 43 HH subjects, age 30-74 (50 +/- 10, mean +/- SD), and 37 consecutive visits of 21 normal volunteers, age 30-63 (48 +/- 8), were evaluated over a 3-year period. SR was obtained from the basal septum in apical four-chamber views. All patients had confirmed C282Y homozygosity, a documented history of iron overload, and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. In the HH subjects, the SR demonstrated moderate but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect.

Fluid overload in the ICU: evaluation and management.

PubMed

Claure-Del Granado, Rolando; Mehta, Ravindra L

2016-08-02

Fluid overload is frequently found in acute kidney injury patients in critical care units. Recent studies have shown the relationship of fluid overload with adverse outcomes; hence, manage and optimization of fluid balance becomes a central component of the management of critically ill patients. In critically ill patients, in order to restore cardiac output, systemic blood pressure and renal perfusion an adequate fluid resuscitation is essential. Achieving an appropriate level of volume management requires knowledge of the underlying pathophysiology, evaluation of volume status, and selection of appropriate solution for volume repletion, and maintenance and modulation of the tissue perfusion. Numerous recent studies have established a correlation between fluid overload and mortality in critically ill patients. Fluid overload recognition and assessment requires an accurate documentation of intakes and outputs; yet, there is a wide difference in how it is evaluated, reviewed and utilized. Accurate volume status evaluation is essential for appropriate therapy since errors of volume evaluation can result in either in lack of essential treatment or unnecessary fluid administration, and both scenarios are associated with increased mortality. There are several methods to evaluate fluid status; however, most of the tests currently used are fairly inaccurate. Diuretics, especially loop diuretics, remain a valid therapeutic alternative. Fluid overload refractory to medical therapy requires the application of extracorporeal therapies. In critically ill patients, fluid overload is related to increased mortality and also lead to several complications like pulmonary edema, cardiac failure, delayed wound healing, tissue breakdown, and impaired bowel function. Therefore, the evaluation of volume status is crucial in the early management of critically ill patients. Diuretics are frequently used as an initial therapy; however, due to their limited effectiveness the use of continuous renal replacement techniques are often required for fluid overload treatment. Successful fluid overload treatment depends on precise assessment of individual volume status, understanding the principles of fluid management with ultrafiltration, and clear treatment goals.

Effects of Frequent Hemodialysis on Ventricular Volumes and Left Ventricular Remodeling

PubMed Central

Greene, Tom; Chertow, Glenn M.; Kliger, Alan S.; Stokes, John B.; Beck, Gerald J.; Daugirdas, John T.; Kotanko, Peter; Larive, Brett; Levin, Nathan W.; Mehta, Ravindra L.; Rocco, Michael; Sanz, Javier; Yang, Phillip C.; Rajagopalan, Sanjay

2013-01-01

Summary Background and objectives Higher left ventricular volume is associated with death in patients with ESRD. This work investigated the effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling. Design, setting, participants, & measurements The Frequent Hemodialysis Network daily trial randomized 245 patients to 12 months of six times per week versus three times per week in-center hemodialysis; the Frequent Hemodialysis Network nocturnal trial randomized 87 patients to 12 months of six times per week nocturnal hemodialysis versus three times per week predominantly home-based hemodialysis. Left and right ventricular end systolic and diastolic volumes, left ventricular mass, and ejection fraction at baseline and end of the study were ascertained by cardiac magnetic resonance imaging. The ratio of left ventricular mass/left ventricular end diastolic volume was used as a surrogate marker of left ventricular remodeling. In each trial, the effect of frequent dialysis on left or right ventricular end diastolic volume was tested between predefined subgroups. Results In the daily trial, frequent hemodialysis resulted in significant reductions in left ventricular end diastolic volume (−11.0% [95% confidence interval, −16.1% to −5.5%]), left ventricular end systolic volume (−14.8% [−22.7% to −6.2%]), right ventricular end diastolic volume (−11.6% [−19.0% to −3.6%]), and a trend for right ventricular end systolic volume (−11.3% [−21.4% to 0.1%]) compared with conventional therapy. The magnitude of reduction in left and right ventricular end diastolic volumes with frequent hemodialysis was accentuated among patients with residual urine output<100 ml/d (P value [interaction]=0.02). In the nocturnal trial, there were no significant changes in left or right ventricular volumes. The frequent dialysis interventions had no substantial effect on the ratio of left ventricular mass/left ventricular end diastolic volume in either trial. Conclusions Frequent in-center hemodialysis reduces left and right ventricular end systolic and diastolic ventricular volumes as well as left ventricular mass, but it does not affect left ventricular remodeling. PMID:23970131

Unfavorable effects of history of volume overload and late referral to a nephrologist on mortality in patients initiating dialysis: a multicenter prospective cohort study in Japan.

PubMed

Okazaki, Masaki; Inaguma, Daijo; Imaizumi, Takahiro; Kada, Akiko; Yaomura, Takaaki; Tsuboi, Naotake; Maruyama, Shoichi

2018-03-14

Patients with late referral and positive history of volume overload may have a poor prognosis after initiating dialysis due to insufficient and/or inadequate management of complications of renal failure and the lack of better dialysis preparation. Little is known about the influence of the relationship between history of volume overload and late referral on prognosis. We analyzed 1475 patients who had initiated dialysis for the first time from October 2011 to September 2013. late referral was defined as referral to a nephrologist < 3 months before dialysis initiation. The major outcomes were all-cause death and deaths due to cardiovascular diseases (CVD). The impact of late referral and history of volume overload on all-cause mortality was assessed by Cox proportional hazards models. Among 1475 patients, the mean patient age was 67.5 years. During the median follow-up of 2.2 years, 260 deaths occurred; 99 were due to CVD. Cox proportional hazards models demonstrated that late referral (adjusted hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.00-1.82) and history of volume overload (adjusted HR, 1.39; 95% CI, 1.06-1.81) were risk factors for all-cause mortality. Furthermore, late referral coexisting was associated with a history of volume overload increased mortality (adjusted HR, 2.10; 95% CI, 1.39-3.16 versus absence of late referral without history of volume overload) after adjusting for age, sex, diabetes, atherosclerotic disease, and laboratory values. Both late referral and history of volume overload were associated with increased risks of all-cause mortality. University Hospital Medical Information Network (UMIN000007096). Registered 18 January 2012, retrospectively registered. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008349 .

Protecting Mitochondrial Bioenergetic Function during Resuscitation from Cardiac Arrest

PubMed Central

Gazmuri, Raúl J.; Radhakrishnan, Jeejabai

2012-01-01

Synopsis Successful resuscitation from cardiac arrest requires reestablishment of aerobic metabolism by reperfusion with oxygenated blood of tissues that have been deprived of oxygen for variables periods of time. However, reperfusion concomitantly activates pathogenic mechanisms known as “reperfusion injury.” At the core of reperfusion injury are mitochondria, playing a critical role as effectors and targets of such injury. Mitochondrial injury compromises oxidative phosphorylation and also prompts release of cytochrome c to the cytosol and bloodstream where it correlates with severity of injury. Main drivers of such injury include Ca2+ overload and oxidative stress. Preclinical work shows that limiting myocardial cytosolic Na+ overload at the time of reperfusion attenuates mitochondrial Ca2+ overload and maintains oxidative phosphorylation yielding functional myocardial benefits that include preservation of left ventricular distensibility. Preservation of left ventricular distensibility enables hemodynamically more effective chest compression. Similar myocardial effect have been reported using erythropoietin hypothesized to protect mitochondrial bioenergetic function presumably through activation of pathways similar to those activated during preconditioning. Incorporation of novel and clinical relevant strategies to protect mitochondrial bioenergetic function are expected to attenuate injury at the time of reperfusion and enhance organ viability ultimately improving resuscitation and survival from cardiac arrest. PMID:22433486

Pituitary iron and volume predict hypogonadism in transfusional iron overload.

PubMed

Noetzli, Leila J; Panigrahy, Ashok; Mittelman, Steven D; Hyderi, Aleya; Dongelyan, Ani; Coates, Thomas D; Wood, John C

2012-02-01

Hypogonadism is the most common morbidity in patients with transfusion-dependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary R2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with Blackfan-Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < -2.5) were independently predictive of hypogonadism. Pituitary R2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas R2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac R2* and ferritin were retained on multivariate regression with a combined r(2) of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderate-to-severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Copyright © 2011 Wiley Periodicals, Inc.

Cartilage intermediate layer protein-1 alleviates pressure overload-induced cardiac fibrosis via interfering TGF-β1 signaling.

PubMed

Zhang, Cheng-Lin; Zhao, Qian; Liang, Hui; Qiao, Xue; Wang, Jin-Yu; Wu, Dan; Wu, Li-Ling; Li, Li

2018-03-01

Cardiac fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins in the myocardium and results in decreased ventricular compliance and diastolic dysfunction. Cartilage intermediate layer protein-1 (CILP-1), a novel identified cardiac matricellular protein, is upregulated in most conditions associated with cardiac remodeling, however, whether CILP-1 is involved in pressure overload-induced fibrotic response is unknown. Here, we investigated whether CILP-1 was critically involved in the fibrotic remodeling induced by pressure overload. Western blot analysis and immunofluorescence staining showed that CILP-1 was predominantly detected in cardiac myocytes and to a less extent in the interstitium. In isolated adult mouse ventricular myocytes and nonmyocytes, CILP-1 was found to be mainly synthesized by myocytes. CILP-1 expression in left ventricles was upregulated in C57BL/6 mice undergoing transverse aortic constriction (TAC). Myocardial CILP-1 knockdown aggravated whereas CILP-1 overexpression attenuated TAC-induced ventricular remodeling and dysfunction, as measured by echocardiography test, morphological examination, and gene expressions of fibrotic molecules. Incubation of cardiac fibroblasts with the conditioned medium containing full-length, N-terminal, or C-terminal CILP-1 inhibited transforming growth factor (TGF)-β1-induced Smad3 phosphorylation and the subsequent profibrotic events. We first demonstrated that C-terminal CILP-1 increased Akt phosphorylation, promoted the interaction between Akt and Smad3, and suppressed Smad3 phosphorylation. Blockade of PI3K-Akt pathway attenuated the inhibitory effect of C-CILP-1 on TGF-β1-induced Smad3 activation. We conclude that CILP-1 is a novel ECM protein possessing anti-fibrotic ability in pressure overload-induced fibrotic remodeling. This anti-fibrotic effect of CILP-1 attributes to interfering TGF-β1 signaling through its N- and C- terminal fragments. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Role of melatonin in calcium overload-induced heart injury].

PubMed

Kong, Lingheng; Wei, Ming; Sun, Na; Zhu, Juanxia; Su, Xingli

2017-06-28

To investigate the role of melatonin in calcium overload-induced heart injury.
 Methods: Thirty-two rats were divided into 4 groups: a control group (Control), a melatonin control group (Mel), a calcium overload group (CaP), and a calcium overload plus melatonin group (Mel+CaP). Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium. Lactate dehydrogenase (LDH) activity in the coronary flow was determined. The expressions of caspase-3 and cytochrome c were determined by Western blot. The pathological morphological changes in myocardial fiber were analyzed by HE staining.
 Results: Compared with the control group, calcium overload significantly induced an enlarged infarct size (P<0.01), accompanied by the disordered arrangement of myocardial fiber, up-regulation of cytochrome c and caspase-3 (P<0.01), and the increased activity of LDH (P<0.01). These effects were significantly attenuated by 10 μmol/L melatonin (P<0.01).
 Conclusion: Melatonin can alleviate calcium overload-induced heart injury.

Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study.

PubMed

Fukunami, Masatake; Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru

2011-12-01

Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload. Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters. Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days. This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.

Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies.

PubMed

Hung, Szu-Chun; Lai, Yi-Shin; Kuo, Ko-Lin; Tarng, Der-Cherng

2015-05-05

Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease (CKD). However, the relationship between volume overload and adverse outcomes in CKD is not fully understood. A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end-stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD. We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high-salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor-α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes. Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Microtubule Actin Cross-Linking Factor 1 Regulates Cardiomyocyte Microtubule Distribution and Adaptation to Hemodynamic Overload

PubMed Central

Kwak, Dongmin; Wang, Huan; Liu, Xiaoyu; Hu, Xinli; Bache, Robert J.; Chen, Yingjie

2013-01-01

Aberrant cardiomyocyte microtubule growth is a feature of pressure overload induced cardiac hypertrophy believed to contribute to left ventricular (LV) dysfunction. Microtubule Actin Cross-linking Factor 1 (MACF1/Acf7) is a 600 kd spectraplakin that stabilizes and guides microtubule growth along actin filaments. MACF1 is expressed in the heart, but its impact on cardiac microtubules, and how this influences cardiac structure, function, and adaptation to hemodynamic overload is unknown. Here we used inducible cardiac-specific MACF1 knockout mice (MACF1 KO) to determine the impact of MACF1 on cardiac microtubules and adaptation to pressure overload (transverse aortic constriction (TAC).In adult mouse hearts, MACF1 expression was low under basal conditions, but increased significantly in response to TAC. While MACF1 KO had no observable effect on heart size or function under basal conditions, MACF1 KO exacerbated TAC induced LV hypertrophy, LV dilation and contractile dysfunction. Interestingly, subcellular fractionation of ventricular lysates revealed that MACF1 KO altered microtubule distribution in response to TAC, so that more tubulin was associated with the cell membrane fraction. Moreover, TAC induced microtubule redistribution into this cell membrane fraction in both WT and MACF1 KO mice correlated strikingly with the level of contractile dysfunction (r2 = 0.786, p<.001). MACF1 disruption also resulted in reduction of membrane caveolin 3 levels, and increased levels of membrane PKCα and β1 integrin after TAC, suggesting MACF1 function is important for spatial regulation of several physiologically relevant signaling proteins during hypertrophy. Together, these data identify for the first time, a role for MACF1 in cardiomyocyte microtubule distribution and in adaptation to hemodynamic overload. PMID:24086300

Microtubule Actin Cross-linking Factor 1 regulates cardiomyocyte microtubule distribution and adaptation to hemodynamic overload.

PubMed

Fassett, John T; Xu, Xin; Kwak, Dongmin; Wang, Huan; Liu, Xiaoyu; Hu, Xinli; Bache, Robert J; Chen, Yingjie

2013-01-01

Aberrant cardiomyocyte microtubule growth is a feature of pressure overload induced cardiac hypertrophy believed to contribute to left ventricular (LV) dysfunction. Microtubule Actin Cross-linking Factor 1 (MACF1/Acf7) is a 600 kd spectraplakin that stabilizes and guides microtubule growth along actin filaments. MACF1 is expressed in the heart, but its impact on cardiac microtubules, and how this influences cardiac structure, function, and adaptation to hemodynamic overload is unknown. Here we used inducible cardiac-specific MACF1 knockout mice (MACF1 KO) to determine the impact of MACF1 on cardiac microtubules and adaptation to pressure overload (transverse aortic constriction (TAC).In adult mouse hearts, MACF1 expression was low under basal conditions, but increased significantly in response to TAC. While MACF1 KO had no observable effect on heart size or function under basal conditions, MACF1 KO exacerbated TAC induced LV hypertrophy, LV dilation and contractile dysfunction. Interestingly, subcellular fractionation of ventricular lysates revealed that MACF1 KO altered microtubule distribution in response to TAC, so that more tubulin was associated with the cell membrane fraction. Moreover, TAC induced microtubule redistribution into this cell membrane fraction in both WT and MACF1 KO mice correlated strikingly with the level of contractile dysfunction (r(2) = 0.786, p<.001). MACF1 disruption also resulted in reduction of membrane caveolin 3 levels, and increased levels of membrane PKCα and β1 integrin after TAC, suggesting MACF1 function is important for spatial regulation of several physiologically relevant signaling proteins during hypertrophy. Together, these data identify for the first time, a role for MACF1 in cardiomyocyte microtubule distribution and in adaptation to hemodynamic overload.

Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation.

PubMed

Chen, Mei-Pian; Li, Shu-Na; Lam, Wendy W M; Ho, Yuen-Chi; Ha, Shau-Yin; Chan, Godfrey C F; Cheung, Yiu-Fai

2014-04-12

Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin. In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products. Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.

Left ventricular rotation and right-left ventricular interaction in congenital heart disease: the acute effects of interventional closure of patent arterial ducts and atrial septal defects.

PubMed

Laser, Kai T; Haas, Nikolaus A; Fischer, Markus; Habash, Sheeraz; Degener, Franziska; Prinz, Christian; Körperich, Hermann; Sandica, Eugen; Kececioglu, Deniz

2014-08-01

Left ventricular rotation is physiologically affected by acute changes in preload. We investigated the acute effect of preload changes in chronically underloaded and overloaded left ventricles in children with shunt lesions. A total of 15 patients with atrial septal defects (Group A: 7.4 ± 4.7 years, 11 females) and 14 patients with patent arterial ducts (Group B: 2.7 ± 3.1 years, 10 females) were investigated using 2D speckle-tracking echocardiography before and after interventional catheterisation. The rotational parameters of the patient group were compared with those of 29 matched healthy children (Group C). Maximal torsion (A: 2.45 ± 0.9°/cm versus C: 1.8 ± 0.8°/cm, p < 0.05), apical peak systolic rotation (A: 12.6 ± 5.7° versus C: 8.7 ± 3.5°, p < 0.05), and the peak diastolic torsion rate (A: -147 ± 48°/second versus C: -110 ± 31°/second, p < 0.05) were elevated in Group A and dropped immediately to normal values after intervention (maximal torsion 1.5 ± 1.1°/cm, p < 0.05, apical peak systolic rotation 7.2 ± 4.1°, p < 0.05, and peak diastolic torsion rate -106 ± 35°/second, p < 0.05). Patients in Group B had decreased maximal torsion (B: 1.8 ± 1.1°/cm versus C: 3.8 ± 1.4°/cm, p < 0.05) and apical peak systolic rotation (B: 8.3 ± 6.1° versus C: 13.9 ± 4.3°, p < 0.05). Defect closure was followed by an increase in maximal torsion (B: 2.7 ± 1.4°/cm, p < 0.05) and the peak diastolic torsion rate (B: -133 ± 66°/second versus -176 ± 84°/second, p < 0.05). Patients with chronically underloaded left ventricles compensate with an enhanced apical peak systolic rotation, maximal torsion, and quicker diastolic untwisting to facilitate diastolic filling. In patients with left ventricular dilatation by volume overload, the peak systolic apical rotation and the maximal torsion are decreased. After normalisation of the preload, they immediately return to normal and diastolic untwisting rebounds. These mechanisms are important for understanding the remodelling processes.

Pressure-volume analysis reveals characteristic sex-related differences in cardiac function in a rat model of aortic banding-induced myocardial hypertrophy.

PubMed

Ruppert, Mihály; Korkmaz-Icöz, Sevil; Loganathan, Sivakkanan; Jiang, Weipeng; Lehmann, Lorenz H; Oláh, Attila; Sayour, Alex Ali; Barta, Bálint András; Merkely, Béla; Karck, Matthias; Radovits, Tamás; Szabó, Gábor

2018-05-25

Sex differences in pressure overload (PO)-induced left ventricular (LV) myocardial hypertrophy (LVH) have been intensely investigated. Nevertheless, sex-related disparities of LV hemodynamics in LVH were not examined in detail. Therefore, we aimed to provide a detailed characterization of distinct aspects of LV function in male and female rats during different stages of LVH. Banding of the abdominal aorta (AB) was performed to induce PO for 6 or 12 weeks in male and female rats. Control animals underwent sham operation. The development of LVH was followed by serial echocardiography. Cardiac function was assessed by pressure-volume analysis. Cardiomyocyte hypertrophy and fibrosis were evaluated by histology. At week 6, increased LV mass index, heart weight-to-tibial length, cardiomyocyte diameter, concentric LV geometry and moderate interstitial fibrosis were detected in both male and female AB rats, indicating the development of an early stage of LVH. Functionally, at this time point, impaired active relaxation, increased contractility and preserved ventricular-arterial coupling were observed in the AB groups in both genders. In contrast, at week 12, progressive deterioration of LVH-associated structural and functional alterations occurred in male but not in female animals with sustained PO. Accordingly, at this later stage, LVH was associated with eccentric remodeling, exacerbated fibrosis and increased chamber stiffness in male AB rats. Furthermore, augmented contractility declined in male and not in female AB animals, resulting in contractility-afterload mismatch. Maintained contractility augmentation, preserved ventricular-arterial coupling and better myocardial compliance in female rats contribute to sex differences in LV function during the progression of PO-induced LVH.

Time course of right ventricular pressure-overload induced myocardial fibrosis: relationship to changes in fibroblast postsynthetic procollagen processing.

PubMed

Baicu, Catalin F; Li, Jiayu; Zhang, Yuhua; Kasiganesan, Harinath; Cooper, George; Zile, Michael R; Bradshaw, Amy D

2012-11-01

Myocardial fibrillar collagen is considered an important determinant of increased ventricular stiffness in pressure-overload (PO)-induced cardiac hypertrophy. Chronic PO was created in feline right ventricles (RV) by pulmonary artery banding (PAB) to define the time course of changes in fibrillar collagen content after PO using a nonrodent model and to determine whether this time course was dependent on changes in fibroblast function. Total, soluble, and insoluble collagen (hydroxyproline), collagen volume fraction (CVF), and RV end-diastolic pressure were assessed 2 days and 1, 2, 4, and 10 wk following PAB. Fibroblast function was assessed by quantitating the product of postsynthetic processing, insoluble collagen, and levels of SPARC (secreted protein acidic and rich in cysteine), a protein that affects procollagen processing. RV hypertrophic growth was complete 2 wk after PAB. Changes in RV collagen content did not follow the same time course. Two weeks after PAB, there were elevations in total collagen (control RV: 8.84 ± 1.03 mg/g vs. 2-wk PAB: 11.50 ± 0.78 mg/g); however, increased insoluble fibrillar collagen, as measured by CVF, was not detected until 4 wk after PAB (control RV CVF: 1.39 ± 0.25% vs. 4-wk PAB: 4.18 ± 0.87%). RV end-diastolic pressure was unchanged at 2 wk, but increased until 4 wk after PAB. RV fibroblasts isolated after 2-wk PAB had no changes in either insoluble collagen or SPARC expression; however, increases in insoluble collagen and in levels of SPARC were detected in RV fibroblasts from 4-wk PAB. Therefore, the time course of PO-induced RV hypertrophy differs significantly from myocardial fibrosis and diastolic dysfunction. These temporal differences appear dependent on changes in fibroblast function.

Time course of right ventricular pressure-overload induced myocardial fibrosis: relationship to changes in fibroblast postsynthetic procollagen processing

PubMed Central

Baicu, Catalin F.; Li, Jiayu; Zhang, Yuhua; Kasiganesan, Harinath; Cooper, George; Zile, Michael R.

2012-01-01

Myocardial fibrillar collagen is considered an important determinant of increased ventricular stiffness in pressure-overload (PO)-induced cardiac hypertrophy. Chronic PO was created in feline right ventricles (RV) by pulmonary artery banding (PAB) to define the time course of changes in fibrillar collagen content after PO using a nonrodent model and to determine whether this time course was dependent on changes in fibroblast function. Total, soluble, and insoluble collagen (hydroxyproline), collagen volume fraction (CVF), and RV end-diastolic pressure were assessed 2 days and 1, 2, 4, and 10 wk following PAB. Fibroblast function was assessed by quantitating the product of postsynthetic processing, insoluble collagen, and levels of SPARC (secreted protein acidic and rich in cysteine), a protein that affects procollagen processing. RV hypertrophic growth was complete 2 wk after PAB. Changes in RV collagen content did not follow the same time course. Two weeks after PAB, there were elevations in total collagen (control RV: 8.84 ± 1.03 mg/g vs. 2-wk PAB: 11.50 ± 0.78 mg/g); however, increased insoluble fibrillar collagen, as measured by CVF, was not detected until 4 wk after PAB (control RV CVF: 1.39 ± 0.25% vs. 4-wk PAB: 4.18 ± 0.87%). RV end-diastolic pressure was unchanged at 2 wk, but increased until 4 wk after PAB. RV fibroblasts isolated after 2-wk PAB had no changes in either insoluble collagen or SPARC expression; however, increases in insoluble collagen and in levels of SPARC were detected in RV fibroblasts from 4-wk PAB. Therefore, the time course of PO-induced RV hypertrophy differs significantly from myocardial fibrosis and diastolic dysfunction. These temporal differences appear dependent on changes in fibroblast function. PMID:22942178

Lack of association between chronic exposure to biomass fuel smoke and markers of right ventricular pressure overload at high altitude

PubMed Central

Caravedo, Maria A.; Painschab, Matthew S.; Davila-Roman, Victor G.; De Ferrari, Aldo; Gilman, Robert H.; Vasquez-Villar, Angel D.; Pollard, Suzanne L.; Miranda, J. Jaime; Checkley, William

2014-01-01

Background Chronic exposure to biomass fuel smoke has been implicated in the development of pulmonary hypertension and right ventricular pressure/volume overload through activation of inflammation, increase in vascular resistance and endothelial dysfunction. We sought to compare N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and echocardiography-derived pulmonary artery systolic pressure (PASP) levels in a high-altitude population-based study in Peru with and without chronic exposure to biomass fuel smoke. Methods NT-pro-BNP levels were measured in 519 adults (275 with and 244 without chronic exposure to biomass fuel smoke). Participants answered sociodemographics and clinical history questionnaires, underwent a clinical examination and blood testing for cardiopulmonary biomarkers. PASP was measured in a subgroup of 153 (31%) subjects. Results The study group consisted of 280 men (54%) and 239 women (46%). Average age was 56 years and average body mass index was 27 kg/m2. In multivariable analysis, there was no association between chronic exposure to biomass fuel smoke and NT-pro-BNP (p=0.31) or PASP (p=0.31). In the subgroup in which both NT-pro-BNP levels and PASP were measured, there was strong evidence of an association between these two variables (ρ=0.24, 95% CI 0.09-0.39; p=0.003). We found that age, high sensitivity C-reactive protein, being male and systolic blood pressure were positively associated with NT-pro-BNP levels whereas body mass index, LDL/HDL ratio and HOMA-IR were negatively associated (all p<0.01). Conclusions In this population-based study in a high-altitude setting, neither NT-pro-BNP levels nor echocardiography-derived PASP were associated with chronic exposure to biomass fuel smoke. PMID:25440802

Transcatheter closure of left ventricle to right atrial communication using cera duct occluder.

PubMed

Ganesan, Gnanavelu; Paul, G Justin; Mahadevan, Vaikom S

Left ventricle-right atrial communication could be congenital (Gerbode defect) or acquired as a complication of surgery or infective endocarditis and leads to volume overloading of pulmonary circulation. Two types, direct and indirect types are known depending on the involvement of septal tricuspid leaflet. Transcatheter closure of this defect is feasible and appears an attractive alternative to surgical management. Various devices like Amplatzer duct occluder I, II, Muscular ventricular septal defect device etc. have been used to close this defect. We report two patients, a preteen boy with direct left ventricle-right atrial communication as post operative complication and an adult female with indirect communication who underwent transcatheter closure with Cera duct occluder (Lifetech Scientific (Shenzhen), China). Copyright © 2017. Published by Elsevier B.V.

Aconitine-induced Ca{sup 2+} overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

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

Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao

Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na{sup +} channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca{sup 2+} in aconitine poisoning. In this study, we explored the importance of pathological Ca{sup 2+} signaling in aconitine poisoning in vitro and in vivo. We found that Ca{sup 2+} overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicitymore » assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca{sup 2+} handling proteins demonstrated that aconitine promoted Ca{sup 2+} overload through the expression regulation of Ca{sup 2+} handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca{sup 2+} overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca{sup 2+} overload causes arrhythmia in rats. • Aconitine induces Ca{sup 2+} overload through the activation of L-type Ca{sup 2+} channels. • Aconitine-induced Ca{sup 2+} overload triggers apoptotic responses in vitro and in vivo. • Aconitine promotes apoptotic development via activation of P38 MAPK.« less

Variation in practice patterns in device closure of atrial septal defects and patent ductus arteriosus: An analysis of data from the IMproving Pediatric and Adult Congenital Treatment (IMPACT) registry.

PubMed

O'Byrne, Michael L; Kennedy, Kevin F; Rome, Jonathan J; Glatz, Andrew C

2018-02-01

Practice variation is a potentially important measure of healthcare quality. The IMPACT registry provides a representative national sample with which to study practice variation in trans-catheter interventions for congenital heart disease. We studied cases for closure of atrial septal defect (ASD) and patent ductus arteriosus (PDA) in IMPACT between January 1, 2011, and September 30, 2015, using hierarchical multivariate models studying (1) the distribution of indications for closure and (2) in patients whose indication for closure was left (LVVO) or right ventricular volume overload (RVVO), the factors influencing probability of closure of a small defect (either in size or in terms of the magnitude of shunt). Over the study period, 5233 PDA and 4459 ASD cases were performed at 77 hospitals. The indications for ASD closure were RVVO in 84% and stroke prevention in 13%. Indications for PDA closure were LVVO in 57%, endocarditis prevention in 36%, and pulmonary hypertension in 7%. There was statistically significant variability in indications between hospitals for PDA and ASD procedures (median rate ratio (MRR): 1.3 and 1.1; both P<.001). The proportion of cases for volume overload with a Qp:Qs <1.5:1 decreased with increasing PDA and ASD procedural volume (P=.04 and 0.05). For ASD, the proportion was higher at hospitals with a larger proportion of adult cases (P=.0007). There was significant variation in practice in the risk of closing PDA <2 mm for LVVO (MRR: 1.4, P<.001). There is measurable variation in transcatheter closure of PDA and ASD. Further research is necessary to study whether this affects outcomes or resource utilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice.

PubMed

Ji, Xiao-Bing; Li, Xiu-Rong; Hao-Ding; Sun, Qi; Zhou, Yang; Wen, Ping; Dai, Chun-Sun; Yang, Jun-Wei

2015-01-01

Uncoupling protein 2 (UCP2) is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC), and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip) or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls). ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload. © 2015 S. Karger AG, Basel.

Partial anomalous pulmonary venous connection: diagnosis by transesophageal echocardiography.

PubMed

Ammash, N M; Seward, J B; Warnes, C A; Connolly, H M; O'Leary, P W; Danielson, G K

1997-05-01

This study sought to demonstrate that with proper technique, identification of the normal and abnormal pulmonary venous connection can be made with confidence using transesophageal echocardiography (TEE). Partial anomalous pulmonary venous connection (PAPVC) is an uncommon congenital anomaly whose diagnosis has classically been made using angiography. We performed a retrospective review of all patients of all ages with PAPVC diagnosed at the Mayo Clinic who had undergone TEE because of either right ventricular volume overload or suspected intracardiac shunting by transthoracic echocardiography or intraoperatively. A total of 66 PAPVCs were detected in 43 patients (1.5/patient); in 2 additional patients, TEE suggested, but did not diagnose, PAPVCs. Shortness of breath was the most common presenting symptom (42.2%), followed by heart murmur and supraventricular tachycardia. Right-sided anomalous veins were identified in 35 patients (81.4%), left-sided in 7 (16.3%) and bilateral in 1 (2.3%). There was a single anomalous connecting vein in 23 patients (53.5%), two in 18 (41.9%), three in 1 (2.3%) and four in 1 (2.3%). The connecting site was the superior vena cava (SVC) in 39 veins (59.1%), right atrial-SVC junction in 6 (9.1%), right atrium in 8 (12.1%), inferior vena cava in 1 (1.5%) and the coronary sinus in 2 (3.0%). Ten anomalous left pulmonary veins were connected by a vertical vein to the innominate vein (15.1%). Sinus venosus atrial septal defect (ASD) was the most common associated anomaly in 22 patients (49%), followed by ostium secundum ASD in 6 and patent foramen ovale in 4. Fifteen patients had an intact atrial septum. Thirty-one patients (68.8%) underwent surgical repair. PAPVC was confirmed in all patients, including the two whose TEE results were suggestive of PAPVC. All 49 PAPVCs detected by TEE preoperatively were confirmed at the time of operation. TEE is highly diagnostic for PAPVC and can obviate angiography. Accurate anatomic diagnosis may influence the need for medical and surgical management. TEE should be performed in patients with right ventricular volume overload when the precordial examination is inconclusive.

Pituitary iron and volume imaging in healthy controls.

PubMed

Noetzli, L J; Panigrahy, A; Hyderi, A; Dongelyan, A; Coates, T D; Wood, J C

2012-02-01

Patients with transfusional iron overload develop iron deposits in the pituitary gland, which are associated with volume loss and HH. The purpose of this study was to characterize R2 and volumetric data in a healthy population for diagnostic use in patients with transfusional iron overload. One hundred healthy controls without iron overload between the ages of 2 and 48 were recruited to have MR imaging of the brain to assess their pituitary R2 and volume. Pituitary R2 was assessed with a 8-echo spin-echo sequence, and pituitary volumes, by a 3D spoiled gradient-echo sequence with 1-mm(3) resolution. A 2-component continuous piecewise linear approximation was used for creating volumetric and R2 nomograms. Equations were generated from regression relationships for convenient z-score calculation. Pituitary R2 rose weakly with age (r(2) = 0.19, P < .0001). Anterior and total pituitary volumes increased steadily up to 18 years of age, after which volume slightly decreased. Females had larger pituitary glands, most likely representing their larger lactotroph population. From these data, a clinician can calculate the z scores for R2 and pituitary volume in patients with iron overload. Normal ranges are well-differentiated from values previously associated with endocrine disease in transfusional siderosis; this finding suggests that preclinical iron overload can be recognized and appropriately treated.

Exposure to chronic alcohol accelerates development of wall stress and eccentric remodeling in rats with volume overload.

PubMed

Mouton, Alan J; Ninh, Van K; El Hajj, Elia C; El Hajj, Milad C; Gilpin, Nicholas W; Gardner, Jason D

2016-08-01

Chronic alcohol abuse is one of the leading causes of dilated cardiomyopathy (DCM) in the United States. Volume overload (VO) also produces DCM characterized by left ventricular (LV) dilatation and reduced systolic and diastolic function, eventually progressing to congestive heart failure. For this study, we hypothesized that chronic alcohol exposure would exacerbate cardiac dysfunction and remodeling due to VO. Aortocaval fistula surgery was used to induce VO, and compensatory cardiac remodeling was allowed to progress for either 3days (acute) or 8weeks (chronic). Alcohol was administered via chronic intermittent ethanol vapor (EtOH) for 2weeks before the acute study and for the duration of the 8week chronic study. Temporal alterations in LV function were assessed by echocardiography. At the 8week end point, pressure-volume loop analysis was performed by LV catheterization and cardiac tissue collected. EtOH did not exacerbate LV dilatation (end-systolic and diastolic diameter) or systolic dysfunction (fractional shortening, ejection fraction) due to VO. The combined stress of EtOH and VO decreased the eccentric index (posterior wall thickness to end-diastolic diameter ratio), increased end-diastolic pressure (EDP), and elevated diastolic wall stress. VO also led to increases in posterior wall thickness, which was not observed in the VO+EtOH group, and wall thickness significantly correlated with LV BNP expression. VO alone led to increases in interstitial collagen staining (picrosirius red), which while not statistically significant, tended to be decreased by EtOH. VO increased LV collagen I protein expression, whereas in rats with VO+EtOH, LV collagen I was not elevated relative to Sham. The combination of VO and EtOH also led to increases in LV collagen III expression relative to Sham. Rats with VO+EtOH had significantly lower collagen I/III ratio than rats with VO alone. During the acute remodeling phase of VO (3days), VO significantly increased collagen III expression, whereas this effect was not observed in rats with VO+EtOH. In conclusion, chronic EtOH accelerates the development of elevated wall stress and promotes early eccentric remodeling in rats with VO. Our data indicate that these effects may be due to disruptions in compensatory hypertrophy and extracellular matrix remodeling in response to volume overload. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Iron Overload on Cardiac Calcium Regulation: Translational Insights Into Mechanisms and Management of a Global Epidemic.

PubMed

Khamseekaew, Juthamas; Kumfu, Sirinart; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-08-01

Iron overload cardiomyopathy occurs in a rare primary form (ie, hemochromatosis) and a very common secondary form in a host of hemoglobinopathies (eg, thalassemia, sickle cell anemia) of substantial and growing global prevalence, which have transformed iron overload cardiomyopathy into a worldwide epidemic. Intracellular calcium ([Ca(2+)]i) is known to be a critical regulator of myocardial function, in which it plays a key role in maintaining cardiac excitation-contraction coupling. It has been proposed that a disturbance in cardiac calcium regulation is a major contributor to left ventricular dysfunction in iron overload cardiomyopathy. This review comprehensively summarizes reports concerned with the effects of iron overload on cardiac calcium regulation, including alteration in the intracellular calcium level, voltage-gated calcium channel function, and calcium cycling protein activity. Consistent reports, as well as inconsistent findings, from both in vitro and in vivo studies, are presented and discussed. The understanding of these mechanisms has provided important new pathophysiological insights and has led to the development of novel therapeutic and preventive strategies for patients with iron overload cardiomyopathy that are currently in clinical trials. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Magnetic resonance imaging during untreated ventricular fibrillation reveals prompt right ventricular overdistention without left ventricular volume loss.

PubMed

Berg, Robert A; Sorrell, Vincent L; Kern, Karl B; Hilwig, Ronald W; Altbach, Maria I; Hayes, Melinda M; Bates, Kathryn A; Ewy, Gordon A

2005-03-08

Most out-of-hospital ventricular fibrillation (VF) is prolonged (>5 minutes), and defibrillation from prolonged VF typically results in asystole or pulseless electrical activity. Recent visual epicardial observations in an open-chest, open-pericardium model of swine VF indicate that blood flows from the high-pressure arterial system to the lower-pressure venous system during untreated VF, thereby overdistending the right ventricle and apparently decreasing left ventricular size. Therefore, inadequate left ventricular stroke volume after defibrillation from prolonged VF has been postulated as a major contributor to the development of pulseless rhythms. Ventricular dimensions were determined by MRI for 30 minutes of untreated VF in a closed-chest, closed-pericardium model in 6 swine. Within 1 minute of untreated VF, mean right ventricular volume increased by 29% but did not increase thereafter. During the first 5 minutes of untreated VF, mean left ventricular volume increased by 34%. Between 20 and 30 minutes of VF, stone heart occurred as manifested by dramatic thickening of the myocardium and concomitant substantial decreases in left ventricular volume. In this closed-chest swine model of VF, substantial right ventricular volume changes occurred early and did not result in smaller left ventricular volumes. The changes in ventricular volumes before the late development of stone heart do not explain why defibrillation from brief duration VF (<5 minutes) typically results in a pulsatile rhythm with return of spontaneous circulation, whereas defibrillation from prolonged VF (5 to 15 minutes) does not.

The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes

PubMed Central

Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P.; Panayiotidis, Panayiotis

2015-01-01

Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. PMID:26190429

Pathological Left Ventricular Hypertrophy and Stem Cells: Current Evidence and New Perspectives.

PubMed

Marketou, Maria E; Parthenakis, Fragiskos; Vardas, Panos E

2016-01-01

Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes. It is the result of complex mechanisms that include not only an increase in protein synthesis and cell size but also proliferating cardiac progenitor cells and the influx of bone marrow-derived cells developing into cardiomyocytes. Stem and progenitor cells are known to contribute to the renewal of adult mammalian cardiomyocytes in case of myocardial injury or pressure and volume overload. They are activated in LVH and play a regulatory role in myocardial repair. They have high proliferative potential and secrete numerous cytokines, growth factors, and microRNAs that play important roles in cell differentiation, cardiac remodeling, and neovascularization. They are mobilized in response to either mechanical or chemical stimuli, hormones, or pharmacologic agents. Another important source of progenitor cells is the epicardial layer. It appears that precursor cells migrate from the epicardium to the myocardium in order to interact with myocardial cells. In addition, migratory cells participate in the formation of almost all cardiac structures in myocardial hypertrophy. Although the pathophysiological mechanisms are still obscure and further studies are required, their properties may open the door to regenerative cell therapy for the prevention of adverse remodeling.

Differential calcium handling in two canine models of right ventricular pressure overload.

PubMed

Moon, Marc R; Aziz, Abdulhameed; Lee, Anson M; Moon, Cynthia J; Okada, Shoichi; Kanter, Evelyn M; Yamada, Kathryn A

2012-12-01

The purpose of this investigation was to characterize differential right atrial (RA) and ventricular (RV) molecular changes in Ca(2+)-handling proteins consequent to RV pressure overload and hypertrophy in two common, yet distinct models of pulmonary hypertension: dehydromonocrotaline (DMCT) toxicity and pulmonary artery (PA) banding. A total of 18 dogs underwent sternotomy in four groups: (1) DMCT toxicity (n = 5), (2) mild PA banding over 10 wk to match the RV pressure rise with DMCT (n = 5); (3) progressive PA banding to generate severe RV overload (n = 4); and (4) sternotomy only (n = 4). In the right ventricle, with DMCT, there was no change in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) or phospholamban (PLB), but we saw a trend toward down-regulation of phosphorylated PLB at serine-16 (p[Ser-16]PLB) (P = 0.07). Similarly, with mild PA banding, there was no change in SERCA or PLB, but p(Ser-16)PLB was down-regulated by 74% (P < 0.001). With severe PA banding, there was no change in PLB, but SERCA fell by 57% and p(Ser-16)PLB fell by 67% (P < 0.001). In the right atrium, with DMCT, there were no significant changes. With both mild and severe PA banding, p(Ser-16)PLB fell (P < 0.001), but SERCA and PLB did not change. Perturbations in Ca(2+)-handling proteins depend on the degree of RV pressure overload and the model used to mimic the RV effects of pulmonary hypertension. They are similar, but blunted, in the atrium compared with the ventricle. Copyright © 2012 Elsevier Inc. All rights reserved.

The importance of capillary density-stroke work mismatch for right ventricular adaptation to chronic pressure overload.

PubMed

Noly, Pierre-Emmanuel; Haddad, François; Arthur-Ataam, Jennifer; Langer, Nathaniel; Dorfmüller, Peter; Loisel, Fanny; Guihaire, Julien; Decante, Benoit; Lamrani, Lilia; Fadel, Elie; Mercier, Olaf

2017-12-01

Mechanisms of right ventricular (RV) adaptation to chronic pressure overload are not well understood. We hypothesized that a lower capillary density (CD) to stroke work ratio would be associated with more fibrosis and RV maladaptive remodeling. We induced RV chronic pressure overload over a 20-week period in 2 piglet models of pulmonary hypertension; that is, a shunt model (n = 5) and a chronic thromboembolic pulmonary hypertension model (n = 5). We assessed hemodynamic parameters and RV remodeling as well as RV CD, fibrosis, and angiogenic factors expression. Although RV was similarly hypertrophied in both models, maladapted RV remodeling with impaired systolic function was only seen in chronic thromboembolic pulmonary hypertension group members who had lower CD (484 ± 99 vs 1213 ± 74 cap/mm 2 ; P < .01), lower CD to stroke work ratio (0.29 ± 0.07 vs 0.82 ± 0.16; P = .02), higher myocardial fibrosis (15.4% ± 3.8% vs 8.0% ± 2.5%; P < .01), as well as a higher angiogenic and fibrosis factors expression. The RV adaptive response to chronic pressure overload differs between 2 different piglet models of PH. Mismatch between angiogenesis and workload (CD to stroke work ratio) was associated with greater degree of myocardial fibrosis and RV dysfunction and could be a promising index of RV maladaptation. Further studies are needed to understand the underlying mechanisms. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Right ventricular failure resulting from pressure overload: role of intra-aortic balloon counterpulsation and vasopressor therapy.

PubMed

Liakopoulos, Oliver J; Ho, Jonathan K; Yezbick, Aaron B; Sanchez, Elizabeth; Singh, Vivek; Mahajan, Aman

2010-11-01

Augmentation of coronary perfusion may improve right ventricular (RV) failure following acute increases of RV afterload. We investigated whether intra-aortic balloon counterpulsation (IABP) can improve cardiac function by enhancing myocardial perfusion and reversing compromised biventricular interactions using a model of acute pressure overload. In 10 anesthetized pigs, RV failure was induced by pulmonary artery constriction and systemic hypertension strategies with IABP, phenylephrine (PE), or the combination of both were tested. Systemic and ventricular hemodynamics [cardiac index(CI), ventricular pressures, coronary driving pressures (CDP)] were measured and echocardiography was used to assess tricuspid valve regurgitation, septal positioning (eccentricity index (ECI)), and changes in ventricular and septal dimensions and function [myocardial performance index (MPI), peak longitudinal strain]. Pulmonary artery constriction resulted in doubling of RV systolic pressure (54 ± 4mm Hg), RV distension, severe TR (4+) with decreased RV function (strain: -33%; MPI: +56%), septal flattening (Wt%: -35%) and leftward septal shift (ECI:1.36), resulting in global hemodynamic deterioration (CI: -51%; SvO(2): -26%), and impaired CDP (-30%; P<0.05). IABP support alone failed to improve RV function despite higher CDP (+33%; P<0.05). Systemic hypertension by PE improved CDP (+70%), RV function (strain: +22%; MPI: -21%), septal positioning (ECI:1.12) and minimized TR, but LV dysfunction (strain: -25%; MPI: +31%) occurred after LV afterloading (P<0.05). With IABP, less PE (-41%) was needed to maintain hypertension and CDP was further augmented (+25%). IABP resulted in LV unloading and restored LV function, and increased CI (+46%) and SvO(2) (+29%; P<0.05). IABP with minimal vasopressors augments myocardial perfusion pressure and optimizes RV function after pressure-induced failure. Copyright © 2010 Elsevier Inc. All rights reserved.

Subclinical changes in MRI-determined right ventricular volumes and function in subjects with prediabetes and diabetes.

PubMed

Patscheider, Hannah; Lorbeer, Roberto; Auweter, Sigrid; Schafnitzel, Anina; Bayerl, Christian; Curta, Adrian; Rathmann, Wolfgang; Heier, Margit; Meisinger, Christa; Peters, Annette; Bamberg, Fabian; Hetterich, Holger

2018-07-01

The aim of this study was to assess subclinical changes in right ventricular volumes and function in subjects with prediabetes and diabetes and controls without a history of cardiovascular disease. Data from 400 participants in the KORA FF4 study without self-reported cardiovascular disease who underwent 3-T whole-body MRI were obtained. The right ventricle was evaluated using the short axis and a four-chamber view. Diabetes was defined according to WHO criteria. Associations between glucose tolerance and right ventricular parameters were assessed using multivariable adjusted linear regression models. Data from 337 participants were available for analysis. Of these, 43 (13%) had diabetes, 87 (26%) had prediabetes, and 207 (61%) were normoglycaemic controls. There was a stepwise decrease in right ventricular volumes in men with prediabetes and diabetes in comparison with controls, including right ventricular end-diastolic volume (β = -20.4 and β = -25.6, respectively; p ≤ 0.005), right ventricular end-systolic volume (β = -12.3 and β = -12.7, respectively; p ≤ 0.037) and right ventricular stroke volume (β = -8.1 and β = -13.1, respectively, p ≤ 0.016). We did not observe any association between prediabetes or diabetes and right ventricular volumes in women or between prediabetes or diabetes and right ventricular ejection fraction in men and women. This study points towards early subclinical changes in right ventricular volumes in men with diabetes and prediabetes. • MRI was used to detect subclinical changes in right ventricular parameters. • Diabetes mellitus is associated with right ventricular dysfunction. • Impairment of right ventricular volumes seems to occur predominantly in men.

[Atrio-ventricular pressure difference associated with mitral valve motion].

PubMed

Wang, L M; Mori, H; Minezaki, K; Shinozaki, Y; Okino, H

1990-05-01

Pressure difference (PD) across the mitral valve was analyzed by a computer-aided catheter system in dogs. Positive PD (PPD) was consistently traced in the initial phase of rapid filling. While heart rate (HR) was below 100 beat/min, a negative PD (NPD) followed the above PPD. In the period between the NPD and the 2nd PPD due to atrial contraction, PD was kept at zero, while LA and LV pressures were gradually elevated by pulmonary venous return. As HR exceeded 100, 2 positive peaks of PD merged into M-shaped or mono-peaked PD. Through higher inflow resistance produced by artificial mitral stenosis, PPD peak decayed without NPD. In mitral regurgitation with an acute volume overload, all of the PD amplitudes were exaggerated. Thus the quick reversal of PD suggested the effect in blood filling process across the mitral valve.

Understanding the heterogeneity in volume overload and fluid distribution in decompensated heart failure is key to optimal volume management: role for blood volume quantitation.

PubMed

Miller, Wayne L; Mullan, Brian P

2014-06-01

This study sought to quantitate total blood volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of volume overload, and the magnitude and distribution of blood volume and body water changes following diuretic therapy. The accurate assessment and management of volume overload in patients with DCHF remains problematic. TBV was measured by a radiolabeled-albumin dilution technique with intravascular volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine interstitial volume contribution to total fluid loss. Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular volume post-diuretic therapy despite large reductions in body weight. Mobilization of interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular volume, however, remained increased at dismissal. The extent, composition, and distribution of volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed volume management with respect to a goal of treating to euvolemia. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Hypertrophic response to hemodynamic overload: role of load vs. renin-angiotensin system activation

NASA Technical Reports Server (NTRS)

Koide, M.; Carabello, B. A.; Conrad, C. C.; Buckley, J. M.; DeFreyte, G.; Barnes, M.; Tomanek, R. J.; Wei, C. C.; Dell'Italia, L. J.; Cooper, G. 4th;

Mechanisms of cardiac hypertrophy in canine volume overload

NASA Technical Reports Server (NTRS)

Matsuo, T.; Carabello, B. A.; Nagatomo, Y.; Koide, M.; Hamawaki, M.; Zile, M. R.; McDermott, P. J.

1998-01-01

This study tested whether the modest hypertrophy that develops in dogs in response to mitral regurgitation is due to a relatively small change in the rate of protein synthesis or, alternatively, is due to a decreased rate of protein degradation. After 3 mo of severe experimental mitral regurgitation, the left ventricular (LV) mass-to-body weight ratio increased by 23% compared with baseline values. This increase in LV mass occurred with a small, but not statistically significant, increase in the fractional rate of myosin heavy chain (MHC) synthesis (Ks), as measured using continuous infusion with [3H]leucine in dogs at 2 wk, 4 wk, and 3 mo after creation of severe mitral regurgitation. Translational efficiency was unaffected by mitral regurgitation as measured by the distribution of MHC mRNA in polysome gradients. Furthermore, there was no detectable increase in translational capacity as measured by either total RNA content or the rate of ribosome formation. These data indicate that translational mechanisms that accelerate the rate of cardiac protein synthesis are not responsive to the stimulus of mitral regurgitation. Most of the growth after mitral regurgitation was accounted for by a decrease in the fractional rate of protein degradation, calculated by subtracting fractional rates of protein accumulation at each time point from the corresponding Ks values. We conclude that 1) volume overload produced by severe mitral regurgitation does not trigger substantial increases in the rate of protein synthesis and 2) the modest increase in LV mass results primarily from a decrease in the rate of protein degradation.

Should Tricuspid Annuloplasty be Performed With Pulmonary Valve Replacement for Pulmonary Regurgitation in Repaired Tetralogy of Fallot?

PubMed

Kurkluoglu, Mustafa; John, Anitha S; Cross, Russell; Chung, David; Yerebakan, Can; Zurakowski, David; Jonas, Richard A; Sinha, Pranava

2015-01-01

Indications for prophylactic tricuspid annuloplasty in patients with pulmonary regurgitation (PR) after tetralogy of Fallot (TOF) repair are unclear and often extrapolated from acquired functional tricuspid regurgitation (TR) data in adults, where despite correction of primary left heart pathology, progressive tricuspid annular dilation is noted beyond a threshold diameter >4 cm (21 mm/m(2)). We hypothesized that unlike in adult functional TR, in pure volume-overload conditions such as patients with PR after TOF, the tricuspid valve size is likely to regress after pulmonary valve replacement (PVR). A total of 43 consecutive patients who underwent PVR from 2005 until 2012 at a single institution were retrospectively reviewed. Absolute and indexed tricuspid annulus diameters (TADs), tricuspid annulus Z-scores, grade of TR along with right ventricular size, and function indices were recorded before and after PVR. Preoperative and postoperative echocardiographic data were available in all patients. A higher tricuspid valve Z-score correlated with greater TR both preoperatively (P = 0.005) and postoperatively (P = 0.02). Overall reductions in the absolute and indexed TAD and tricuspid valve Z-scores were seen postoperatively, with greater absolute as well as percentage reduction seen with larger preoperative TAD index (P = 0.007) and higher tricuspid annulus Z-scores (P = 0.06). In pure volume-overload conditions such as patients with PR after TOF, reduction in the tricuspid valve size is seen after PVR. Concomitant tricuspid annuloplasty should not be considered based on tricuspid annular dilation alone. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload.

PubMed

Yancey, Danielle M; Guichard, Jason L; Ahmed, Mustafa I; Zhou, Lufang; Murphy, Michael P; Johnson, Michelle S; Benavides, Gloria A; Collawn, James; Darley-Usmar, Victor; Dell'Italia, Louis J

2015-03-15

Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine to measure mitochondrial membrane potential. Transmission electron microscopy and immunohistochemistry were used for cardiomyocyte structural assessment. In vitro cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial ROS production and decreased mitochondrial membrane potential, which were significantly improved by MitoQ. ACF had extensive loss of desmin and β₂-tubulin that was paralleled by mitochondrial disorganization, loss of cristae, swelling, and clustering identified by mitochondria complex IV staining and transmission electron microscopy. MitoQ improved mitochondrial structural damage and attenuated desmin loss/degradation evidenced by immunohistochemistry and protein expression. However, LV dilatation and fractional shortening were unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not affect LV dilatation or function in ACF, these experiments suggest a connection of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption and mitochondrial damage in the VO of ACF.

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload

PubMed Central

Yancey, Danielle M.; Guichard, Jason L.; Ahmed, Mustafa I.; Zhou, Lufang; Murphy, Michael P.; Johnson, Michelle S.; Benavides, Gloria A.; Collawn, James; Darley-Usmar, Victor

2015-01-01

Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine to measure mitochondrial membrane potential. Transmission electron microscopy and immunohistochemistry were used for cardiomyocyte structural assessment. In vitro cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial ROS production and decreased mitochondrial membrane potential, which were significantly improved by MitoQ. ACF had extensive loss of desmin and β2-tubulin that was paralleled by mitochondrial disorganization, loss of cristae, swelling, and clustering identified by mitochondria complex IV staining and transmission electron microscopy. MitoQ improved mitochondrial structural damage and attenuated desmin loss/degradation evidenced by immunohistochemistry and protein expression. However, LV dilatation and fractional shortening were unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not affect LV dilatation or function in ACF, these experiments suggest a connection of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption and mitochondrial damage in the VO of ACF. PMID:25599572

Protective effects of acute exercise prior to doxorubicin on cardiac function of breast cancer patients: A proof-of-concept RCT.

PubMed

Kirkham, A A; Shave, R E; Bland, K A; Bovard, J M; Eves, N D; Gelmon, K A; McKenzie, D C; Virani, S A; Stöhr, E J; Warburton, D E R; Campbell, K L

2017-10-15

Preclinical studies have reported that a single treadmill session performed 24h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24h prior to treatment changes this response. Breast cancer patients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h prior to treatment (control, n=11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24-48h after the treatment. Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p≤0.01). Whereas systemic vascular resistance (p<0.01) decreased, and ejection fraction (p=0.02) and systolic strain rate (p<0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p<0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure. The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin. Copyright © 2017 Elsevier B.V. All rights reserved.

III SBC Guidelines on the Analysis and Issuance of Electrocardiographic Reports - Executive Summary

PubMed Central

Pastore, Carlos Alberto; Samesima, Nelson; Pereira-Filho, Horacio Gomes

2016-01-01

The third version of the guidelines covers recently described topics, such as ion channel diseases, acute ischemic changes, the electrocardiogram in athletes, and analysis of ventricular repolarization. It sought to revise the criteria for overloads, conduction disorders, and analysis of data for internet transmission. PMID:27982266

Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

PubMed Central

Afzal, Muhammad R.; Samanta, Anweshan; Xuan, Yu-Ting; Girgis, Magdy; Elias, Harold K; Zhu, Yanqing; Davani, Arash; Yang, Yanjuan; Chen, Xing; Ye, Sheng; Wang, Ou-Li; Chen, Lei; Hauptman, Jeryl; Vincent, Robert J.; Dawn, Buddhadeb

2016-01-01

Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension. PMID:27126808

Premorbid determinants of left ventricular dysfunction in a novel model of gradually induced pressure overload in the adult canine

NASA Technical Reports Server (NTRS)

Koide, M.; Nagatsu, M.; Zile, M. R.; Hamawaki, M.; Swindle, M. M.; Keech, G.; DeFreyte, G.; Tagawa, H.; Cooper, G. 4th; Carabello, B. A.

1997-01-01

BACKGROUND: When a pressure overload is placed on the left ventricle, some patients develop relatively modest hypertrophy whereas others develop extensive hypertrophy. Likewise, the occurrence of contractile dysfunction also is variable. The cause of this heterogeneity is not well understood. METHODS AND RESULTS: We recently developed a model of gradual proximal aortic constriction in the adult canine that mimicked the heterogeneity of the hypertrophic response seen in humans. We hypothesized that differences in outcome were related to differences present before banding. Fifteen animals were studied initially. Ten developed left ventricular dysfunction (dys group). Five dogs maintained normal function (nl group). At baseline, the nl group had a lower mean systolic wall stress (96 +/- 9 kdyne/cm2; dys group, 156 +/- 7 kdyne/cm2; P < .0002) and greater relative left ventricular mass (left ventricular weight [g]/body wt [kg], 5.1 +/- 0.36; dys group, 3.9 +/- 0.26; P < .02). On the basis of differences in mean systolic wall stress at baseline, we predicted outcome in the next 28 dogs by using a cutoff of 115 kdyne/cm2. Eighteen of 20 dogs with baseline mean systolic stress > 115 kdyne/cm2 developed dysfunction whereas 6 of 8 dogs with resting stress < or = 115 kdyne/cm2 maintained normal function. CONCLUSIONS: We conclude that this canine model mimicked the heterogeneous hypertrophic response seen in humans. In the group that eventually developed dysfunction there was less cardiac mass despite 60% higher wall stress at baseline, suggesting a different set point for regulating myocardial growth in the two groups.

Adverse ventricular-ventricular interactions in right ventricular pressure load: Insights from pediatric pulmonary hypertension versus pulmonary stenosis.

PubMed

Driessen, Mieke M P; Hui, Wei; Bijnens, Bart H; Dragulescu, Andreea; Mertens, Luc; Meijboom, Folkert J; Friedberg, Mark K

2016-06-01

Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular interactions in right ventricular pressure overload, demonstrating distinct differences between pediatric pulmonary arterial hypertension (iPAH) and pulmonary stenosis (PS). Altered timing of right ventricular free wall contraction and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency, independent of right ventricular systolic pressure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Left ventricular pressure and volume data acquisition and analysis using LabVIEW.

PubMed

Cassidy, S C; Teitel, D F

1997-03-01

To automate analysis of left ventricular pressure-volume data, we used LabVIEW to create applications that digitize and display data recorded from conductance and manometric catheters. Applications separate data into cardiac cycles, calculate parallel conductance, and calculate indices of left ventricular function, including end-systolic elastance, preload-recruitable stroke work, stroke volume, ejection fraction, stroke work, maximum and minimum derivative of ventricular pressure, heart rate, indices of relaxation, peak filling rate, and ventricular chamber stiffness. Pressure-volume loops can be graphically displayed. These analyses are exported to a text-file. These applications have simplified and automated the process of evaluating ventricular function.

Reversed association between aldosterone and mortality in hemodialysis patients: Role of volume overload.

PubMed

Hung, Szu-Chun; Tarng, Der-Cherng

2016-07-01

The role of aldosterone has expanded from its genomic effects that involve renal sodium transport to nongenomic effects such as cardiac and renal fibrosis. Elevated aldosterone levels are associated with increased mortality in the general population. However, the association is reversed in patients with end-stage renal disease on maintenance hemodialysis. We have shown that the inverse association between aldosterone and mortality in hemodialysis patients is due to the confounding effect of volume overload. Volume overload, which is prevalent in patients with chronic kidney disease, is associated with both lower aldosterone concentrations and higher mortality. Our findings support salt and water restriction and treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control. Copyright © 2016 Elsevier Inc. All rights reserved.

'Athlete's heart' in prepubertal children.

PubMed

Rowland, T W; Delaney, B C; Siconolfi, S F

1987-05-01

Bradycardia, cardiomegaly, heart murmurs, and ECG changes are typically observed in adult endurance athletes, but frequency of such changes among children involved in sports training is unclear. Pediatricians need to be aware of whether these features of the "athlete's heart" occur in their patients, because such features may mimic those of cardiac disease. Fourteen prepubertal competitive male swimmers were evaluated by physical examination, ECG and echocardiogram, and findings were compared to those of a group of active but nontrained control boys. Lower resting heart rates and echocardiographic manifestations of chronic left ventricular volume overload were observed among the swimmers. These changes were not manifest on physical examination, however, and no significant ECG alterations were identified among the athletes. These findings indicate that, although features of the athlete's heart are present in children involved in endurance training, seldom will these findings simulate heart disease or be apparent on routine clinical examination.

Investigation of membranous ventricular septal defect complicated with tricuspid regurgitation in ventricular septal defect occlusion

PubMed Central

LIU, SHU-PING; LI, LI; YAO, KE-CHUN; WANG, NA; WANG, JIAN-CHANG

2013-01-01

This study aimed to explore the mechanism of membranous ventricular septal defect complicated with tricuspid regurgitation and the significance of ventricular septal defect occlusion by echocardiography. A total of 43 patients with membranous ventricular septal defect complicated with tricuspid regurgitation were observed by echocardiography and the changes in length, area and volume of tricuspid regurgitation prior to and following ventricular septal defect occlusion were measured. There were four different mechanisms of membranous ventricular septal defect complicated with tricuspid regurgitation. The various indices of tricuspid regurgitation volume were significantly reduced following occlusion. Ventricular septal defect occlusion significantly reduces tricuspid regurgitation volume complicated with membranous ventricular septal defect and echocardiography is an ideal method to detect these changes. PMID:23404058

Viscoelastic properties of pressure overload hypertrophied myocardium: effect of serine protease treatment

NASA Technical Reports Server (NTRS)

Stroud, Jason D.; Baicu, Catalin F.; Barnes, Mary A.; Spinale, Francis G.; Zile, Michael R.

2002-01-01

To determine whether and to what extent one component of the extracellular matrix, fibrillar collagen, contributes causally to abnormalities in viscoelasticity, collagen was acutely degraded by activation of endogenous matrix metalloproteinases (MMPs) with the serine protease plasmin. Papillary muscles were isolated from normal cats and cats with right ventricular pressure overload hypertrophy (POH) induced by pulmonary artery banding. Plasmin treatment caused MMP activation, collagen degradation, decreased the elastic stiffness constant, and decreased the viscosity constant in both normal and POH muscles. Thus, whereas many mechanisms may contribute to the abnormalities in myocardial viscoelasticity in the POH myocardium, changes in fibrillar collagen appear to play a predominant role.

Self organized spatio-temporal structure within the fractured Vadose Zone: The influence of dynamic overloading at fracture intersections

NASA Astrophysics Data System (ADS)

LaViolette, Randall A.; Glass, Robert J.

2004-09-01

Under low flow conditions (where gravity and capillary forces dominate) within an unsaturated fracture network, fracture intersections act as capillary barriers to integrate flow from above and then release it as a pulse below. Water exiting a fracture intersection is often thought to enter the single connected fracture with the lowest invasion pressure. When the accumulated volume varies between intersections, the smaller volume intersections can be overloaded to cause all of the available fractures exiting an intersection to flow. We included the dynamic overloading process at fracture intersections within our previously discussed model where intersections were modeled as tipping buckets connected within a two-dimensional diamond lattice. With dynamic overloading, the flow behavior transitioned smoothly from diverging to converging flow with increasing overload parameter, as a consequence of a heterogeneous field, and they impose a dynamic structure where additional pathways activate or deactivate in time.

Complete atrioventricular canal.

PubMed

Calabrò, Raffaele; Limongelli, Giuseppe

2006-04-05

Complete atrioventricular canal (CAVC), also referred to as complete atrioventricular septal defect, is characterised by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow. CAVC is an uncommon congenital heart disease, accounting for about 3% of cardiac malformations. Atrioventricular canal occurs in two out of every 10,000 live births. Both sexes are equally affected and a striking association with Down syndrome was found. Depending on the morphology of the superior leaflet of the common atrioventricular valve, 3 types of CAVC have been delineated (type A, B and C, according to Rastelli's classification). CAVC results in a significant interatrial and interventricular systemic-to-pulmonary shunt, thus inducing right ventricular pressure and volume overload and pulmonary hypertension. It becomes symptomatic in infancy due to congestive heart failure and failure to thrive. Diagnosis of CAVC might be suspected from electrocardiographic and chest X-ray findings. Echocardiography confirms it and gives anatomical details. Over time, pulmonary hypertension becomes irreversible, thus precluding the surgical therapy. This is the reason why cardiac catheterisation is not mandatory in infants (less than 6 months) but is indicated in older patients if irreversible pulmonary hypertension is suspected. Medical treatment (digitalis, diuretics, vasodilators) plays a role only as a bridge toward surgery, usually performed between the 3rd and 6th month of life.

Potential Adverse Cardiovascular Effects From Excessive Endurance Exercise

PubMed Central

O'Keefe, James H.; Patil, Harshal R.; Lavie, Carl J.; Magalski, Anthony; Vogel, Robert A.; McCullough, Peter A.

2012-01-01

A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity. PMID:22677079

Pathology of myxomatous mitral valve disease in the dog.

PubMed

Fox, Philip R

2012-03-01

Mitral valve competence requires complex interplay between structures that comprise the mitral apparatus - the mitral annulus, mitral valve leaflets, chordae tendineae, papillary muscles, and left atrial and left ventricular myocardium. Myxomatous mitral valve degeneration is prevalent in the canine, and most adult dogs develop some degree of mitral valve disease as they age, highlighting the apparent vulnerability of canine heart valves to injury. Myxomatous valvular remodeling is associated with characteristic histopathologic features. Changes include expansion of extracellular matrix with glycosaminoglycans and proteoglycans; valvular interstitial cell alteration; and attenuation or loss of the collagen-laden fibrosa layer. These lead to malformation of the mitral apparatus, biomechanical dysfunction, and mitral incompetence. Mitral regurgitation is the most common manifestation of myxomatous valve disease and in advanced stages, associated volume overload promotes progressive valvular regurgitation, left atrial and left ventricular remodeling, atrial tears, chordal rupture, and congestive heart failure. Future studies are necessary to identify clinical-pathologic correlates that track disease severity and progression, detect valve dysfunction, and facilitate risk stratification. It remains unresolved whether, or to what extent, the pathobiology of myxomatous mitral valve degeneration is the same between breeds of dogs, between canines and humans, and how these features are related to aging and genetics. Copyright © 2012 Elsevier B.V. All rights reserved.

Acute decrease of left ventricular mechanical dyssynchrony and improvement of contractile state and energy efficiency after left ventricular restoration.

PubMed

Schreuder, Jan J; Castiglioni, Alessandro; Maisano, Francesco; Steendijk, Paul; Donelli, Andrea; Baan, Jan; Alfieri, Ottavio

2005-01-01

Surgical left ventricular restoration by means of endoventricular patch aneurysmectomy in patients with postinfarction aneurysm should result in acute improved left ventricular performance by decreasing mechanical dyssynchrony and increasing energy efficiency. Nine patients with left ventricular postinfarction aneurysm were studied intraoperatively before and after ventricular restoration with a conductance volume catheter to analyze pressure-volume relationships, energy efficiency, and mechanical dyssynchrony. The end-systolic elastance was used as a load-independent index of contractile state. Left ventricular energy efficiency was calculated from stroke work and total pressure-volume area. Segmental volume changes perpendicular to the long axis were used to calculate mechanical dyssynchrony. Statistical analysis was performed with the paired t test and least-squares linear regression. Endoventricular patch aneurysmectomy reduced end-diastolic volume by 37% (P < .001), with unchanged stroke volume. Systolic function improved, as derived from increased +dP/dt(max), by 42% (P < .03), peak ejection rate by 28% (P < .02), and ejection fraction by 16% (P < .0002). Early diastolic function improved, as shown by reduction of -dP/dt(max) by 34% (P < .006) and shortened tau by 30% (P < .001). Left ventricular end-systolic elastance increased from 1.2 +/- 0.6 to 2.2 +/- 1 mm Hg/mL (P < .001). Left ventricular energy efficiency increased by 36% (P < .002). Left ventricular mechanical dyssynchrony decreased during systole by 33% (P < .001) and during diastole by 20% (P < .005). Left ventricular restoration induced acute improvements in contractile state, energy efficiency, and relaxation, together with a decrease in left ventricular mechanical dyssynchrony.

Effects of carvedilol on structural and functional outcomes and plasma biomarkers in the mouse transverse aortic constriction heart failure model.

PubMed

Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J

2017-01-01

Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os ; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma b rain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10-0.12) with the mid- and high-dose carvedilol treatment. A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model.

Effects of carvedilol on structural and functional outcomes and plasma biomarkers in the mouse transverse aortic constriction heart failure model

PubMed Central

Hampton, Caryn; Rosa, Raymond; Szeto, Daphne; Forrest, Gail; Campbell, Barry; Kennan, Richard; Wang, Shubing; Huang, Chin-Hu; Gichuru, Loise; Ping, Xiaoli; Shen, Xiaolan; Small, Kersten; Madwed, Jeffrey; Lynch, Joseph J

2017-01-01

Introduction: Despite the widespread use of the mouse transverse aortic constriction heart failure model, there are no reports on the characterization of the standard-of-care agent carvedilol in this model. Methods: Left ventricular pressure overload was produced in mice by transverse aortic constriction between the innominate and left common carotid arteries. Carvedilol was administered at multiple dose levels (3, 10 and 30 mg/kg/day per os; yielding end-study mean plasma concentrations of 0.002, 0.015 and 0.044 µM, respectively) in a therapeutic design protocol with treatment initiated after the manifestation of left ventricular remodeling at 3 weeks post transverse aortic constriction and continued for 10 weeks. Results: Carvedilol treatment in transverse aortic constriction mice significantly decreased heart rate and left ventricular dP/dt (max) at all dose levels consistent with β-adrenoceptor blockade. The middle dose of carvedilol significantly decreased left ventricular weight, whereas the higher dose decreased total heart, left and right ventricular weight and wet lung weight compared to untreated transverse aortic constriction mice. The higher dose of carvedilol significantly increased cardiac performance as measured by ejection fraction and fractional shortening and decreased left ventricular end systolic volume consistent with the beneficial effect on cardiac function. End-study plasma sST-2 and Gal-3 levels did not differ among sham, transverse aortic constriction control and transverse aortic constriction carvedilol groups. Plasma brain natriuretic peptide concentrations were elevated significantly in transverse aortic constriction control animals (~150%) compared to shams in association with changes in ejection fraction and heart weight and tended to decrease (~30%, p = 0.10–0.12) with the mid- and high-dose carvedilol treatment. Conclusion: A comparison of carvedilol hemodynamic and structural effects in the mouse transverse aortic constriction model versus clinical use indicates a strong agreement in effect profiles preclinical versus clinical, providing important translational validation for this widely used animal model. The present plasma brain natriuretic peptide biomarker findings support the measurement of plasma natriuretic peptides in the mouse transverse aortic constriction model to extend the translational utility of the model. PMID:28491305

Dilation and Hypertrophy: A Cell-Based Continuum Mechanics Approach Towards Ventricular Growth and Remodeling

NASA Astrophysics Data System (ADS)

Ulerich, J.; Göktepe, S.; Kuhl, E.

This manuscript presents a continuum approach towards cardiac growth and remodeling that is capable to predict chronic maladaptation of the heart in response to changes in mechanical loading. It is based on the multiplicative decomposition of the deformation gradient into and elastic and a growth part. Motivated by morphological changes in cardiomyocyte geometry, we introduce an anisotropic growth tensor that can capture both hypertrophic wall thickening and ventricular dilation within one generic concept. In agreement with clinical observations, we propose wall thickening to be a stress-driven phenomenon whereas dilation is introduced as a strain-driven process. The features of the proposed approach are illustrated in terms of the adaptation of thin heart slices and in terms overload-induced dilation in a generic bi-ventricular heart model.

Increased calcium deposits and decreased Ca2+-ATPase in right ventricular myocardium of ascitic broiler chickens.

PubMed

Li, K; Qiao, J; Zhao, L; Dong, S; Ou, D; Wang, J; Wang, H; Xu, T

2006-11-01

Right ventricular hypertrophy and failure is an important step in the development of ascites syndrome (AS) in broiler chickens. Cytoplasmic calcium concentration is a major regulator of cardiac contractile function and various physiological processes in cardiac muscle cells. The purpose of this study was to measure the right ventricular pressure and investigate the precise ultrastructural location of Ca(2+) and Ca(2+)-ATPase in the right ventricular myocardium of chickens with AS induced by low ambient temperature. The results showed that the right ventricular diastolic pressure of ascitic broilers was significantly higher than that of control broilers (P < 0.01), and the maximum change ratio of right intraventricular pressure (RV +/- dp/dt(max)) of ascitic broilers was significantly lower than that of the controls (P < 0.01). Extensively increased calcium deposits were observed in the right ventricular myocardium of ascitic broilers, whereas in the age-matched control broilers, calcium deposits were much less. The Ca(2+)-ATPase reactive products were obviously found on the sarcoplasmic reticulum and mitochondrial membrane of the control right ventricular myocardium, but rarely observed in the ascitic broilers. The data suggest that in ascitic broilers there is the right ventricular diastolic dysfunction, in which the overload of intracellular calcium and the decreased Ca(2+)-ATPase activity might be the important factors.

Augmented endothelial l-arginine transport ameliorates pressure-overload-induced cardiac hypertrophy.

PubMed

Rajapakse, Niwanthi W; Johnston, Tamara; Kiriazis, Helen; Chin-Dusting, Jaye P; Du, Xiao-Jun; Kaye, David M

2015-07-01

What is the central question of this study? What is the potential role of endothelial NO production via overexpression of the l-arginine transporter, CAT1, as a mitigator of cardiac hypertrophy? What is the main finding and its importance? Augmentation of endothelium-specific l-arginine transport via CAT1 can attenuate pressure-overload-dependent cardiac hypertrophy and fibrosis. Our findings support the conclusion that interventions that improve endothelial l-arginine transport may provide therapeutic utility in the setting of myocardial hypertrophy. Such modifications may be introduced by exercise training or locally delivered gene therapy, but further experimental and clinical studies are required. Endothelial dysfunction has been postulated to play a central role in the development of cardiac hypertrophy, probably as a result of reduced NO bioavailability. We tested the hypothesis that increased endothelial NO production, mediated by increased l-arginine transport, could attenuate pressure-overload-induced cardiac hypertrophy. Echocardiography and blood pressure measurements were performed 15 weeks after transverse aortic constriction (TAC) in wild-type (WT) mice (n = 12) and in mice with endothelium-specific overexpression of the l-arginine transporter, CAT1 (CAT+; n = 12). Transverse aortic constriction induced greater increases in heart weight to body weight ratio in WT (by 47%) than CAT+ mice (by 25%) compared with the respective controls (P ≤ 0.05). Likewise, the increase in left ventricular wall thickness induced by TAC was significantly attenuated in CAT+ mice (P = 0.05). Cardiac collagen type I mRNA expression was greater in WT mice with TAC (by 22%; P = 0.03), but not in CAT+ mice with TAC, compared with the respective controls. Transverse aortic constriction also induced lesser increases in β-myosin heavy chain mRNA expression in CAT+ mice compared with WT (P ≤ 0.05). Left ventricular systolic pressure after TAC was 36 and 39% greater in WT and CAT+ mice, respectively, compared with the respective controls (P ≤ 0.001). Transverse aortic constriction had little effect on left ventricular end-diastolic pressure in both genotypes. Taken together, these data indicate that augmenting endothelial function by overexpression of l-arginine transport can attenuate pressure-overload-induced cardiac hypertrophy. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Value of routine investigations to predict loop diuretic down-titration success in stable heart failure.

PubMed

Martens, Pieter; Verbrugge, Frederik H; Boonen, Levinia; Nijst, Petra; Dupont, Matthias; Mullens, Wilfried

2018-01-01

Guidelines advocate down-titration of loop diuretics in chronic heart failure (CHF) when patients have no signs of volume overload. Limited data are available on the expected success rate of this practice or how routine diagnostic tests might help steering this process. Fifty ambulatory CHF-patients on stable neurohumoral blocker/diuretic therapy for at least 3months without any clinical sign of volume overload were prospectively included to undergo loop diuretic down-titration. All patients underwent a similar pre-down-titration evaluation consisting of a dyspnea scoring, physical examination, transthoracic echocardiography (diastolic function, right ventricular function, cardiac filling pressures and valvular disease), blood sample (serum creatinine, plasma NT-pro-BNP and neurohormones). Loop diuretic maintenance dose was subsequently reduced by 50% or stopped if dose was ≤40mg furosemide equivalents. Successful down-titration was defined as a persistent dose reduction after 30days without weight increase >1.5kg or new-onset symptoms of worsening heart failure. At 30-day follow-up, down-titration was successful in 62% (n=31). In 12/19 patients exhibiting down-titration failure, this occurred within the first week. Physical examination, transthoracic echocardiography and laboratory analysis had limited predictive capability to detect patients with down-titration success/failure (positive likelihood-ratios below 1.5, or area under the curve [AUC] non-statically different from AUC=0.5). Loop diuretic down-titration is feasible in a majority of stable CHF patients in which the treating clinician felt continuation of loops was unnecessary to sustain euvolemia. Importantly, routine diagnostics which suggest euvolemia, have limited diagnostic impact on the post-test probability. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulation of the instantaneous inward rectifier and the delayed outward rectifier potassium channels by Captopril and Angiotensin II via the Phosphoinositide-3 kinase pathway in volume-overload-induced hypertrophied cardiac myocytes.

PubMed

Alvin, Zikiar V; Laurence, Graham G; Coleman, Bernell R; Zhao, Aiqiu; Hajj-Moussa, Majd; Haddad, Georges E

2011-07-01

Early development of cardiac hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents can be modulated by the activation of humoral factors, such as angiotensin II (ANG II) through protein kinases. The aim of this work is to assess the regulation of IK and IK1 by ANG II through the PI3-K pathway in hypertrophied ventricular myocytes. Cardiac eccentric hypertrophy was induced through volume-overload in adult male rats by aorto-caval shunt (3 weeks). After one week half of the rats were given captopril (2 weeks; 0.5 g/l/day) and the other half served as control. The voltage-clamp and western blot techniques were used to measure the delayed outward rectifier potassium current (IK) and the instantaneous inward rectifier potassium current (IK1) and Akt activity, respectively. Hypertrophied cardiomyocytes showed reduction in IK and IK1. Treatment with captopril alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10-6M) to cardiocytes treated with captopril reduced IK and IK1 in shunts, but not in sham. Captopril treatment reversed ANG II effects on IK and IK1 in a PI3-K-independent manner. However in the absence of angiotensin converting enzyme inhibition, ANG II increased both IK and IK1 in a PI3-K-dependent manner in hypertrophied cardiomyocytes. Thus, captopril treatment reveals a negative effect of ANG II on IK and IK1, which is PI3-K independent, whereas in the absence of angiotensin converting enzyme inhibition IK and IK1 regulation is dependent upon PI3-K.

Left Ventricular Function in Patients with Pulmonary Arterial Hypertension: The Role of Two-Dimensional Speckle Tracking Strain.

PubMed

de Amorim Corrêa, Ricardo; de Oliveira, Fernanda Brito; Barbosa, Marcia M; Barbosa, Jose Augusto A; Carvalho, Taís Soares; Barreto, Michele Campos; Campos, Frederico Thadeu A F; Nunes, Maria Carmo Pereira

2016-09-01

Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary arterial pressure with abnormal right ventricular (RV) pressure overload that may alter left ventricular (LV) function. The aim of this study was to assess the impact of RV pressure overload on LV function in PAH patients using two-dimensional (2D) speckle tracking strain. The study enrolled 37 group 1 PAH patients and 38 age- and gender-matched healthy controls. LV longitudinal and radial 2D strains were measured with and without including the ventricular septum. Six-minute walk test (6MWT) and brain natriuretic peptide (BNP) levels were also obtained in patients with PAH. The mean age of patients was 46.4 ± 14.8 years, 76% women, and 16 patients (43%) had schistosomiasis. Sixteen patients (43%) were in WHO class III or IV under specific treatment for PAH. The overall 6MWT distance was 441 meters, and the BNP levels were 80 pg/mL. Patients with PAH more commonly presented with LV diastolic dysfunction and impairment of RV function when compared to controls. LV global longitudinal and radial strains were lower in patients than in controls (-17.9 ± 2.8 vs. -20.5 ± 1.9; P < 0.001 and 30.8 ± 10.5 vs. 49.8 ± 15.4; P < 0.001, respectively). After excluding septal values, LV longitudinal and radial strains remained lower in patients than in controls. The independent factors associated with global LV longitudinal strain were LV ejection fraction, RV fractional area change, and tricuspid annular systolic motion. This study showed impaired LV contractility in patients with PAH assessed by speckle tracking strain, irrespective of ventricular septal involvement. Global LV longitudinal strain was associated independently with RV fractional area change and tricuspid annular systolic motion, after adjustment for LV ejection fraction. © 2016, Wiley Periodicals, Inc.

Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy

PubMed Central

Røe, Åsmund T.; Aronsen, Jan Magnus; Skårdal, Kristine; Hamdani, Nazha; Linke, Wolfgang A.; Danielsen, Håvard E.; Sejersted, Ole M.; Sjaastad, Ivar; Louch, William E.

2017-01-01

Abstract Aims Concentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload. Methods and results Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular concentric hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e’ values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. Conclusion In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis. PMID:28472418

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.

PubMed

Kamat, Pranitha; Vandenberghe, Stijn; Christen, Stephan; Bongoni, Anjan K; Meier, Bernhard; Rieben, Robert; Khattab, Ahmed A

2016-01-01

Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R) injury during myocardial infarction (MI). Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS). We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5) or saline (n = 5) was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group) as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE), endothelial cell activation (CD31) and inflammation (IgG, C3b/c, C5b9, MCP-1) were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters.

The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes.

PubMed

Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P; Panayiotidis, Panayiotis

2015-01-01

Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Peripheral Intravenous Volume Assessment (PIVA) for Quantitating Volume Overload in Patients Hospitalized with Acute Decompensated Heart Failure-a Pilot Study.

PubMed

Miles, Merrick; Alvis, Bret D; Hocking, Kyle; Baudenbacher, Franz; Guth, Christy; Lindenfeld, JoAann; Brophy, Colleen; Eagle, Susan

2018-05-16

To determine the feasibility of Peripheral Intravenous Volume Assessment (PIVA) of venous waveforms for assessing volume overload in patients admitted to the hospital with acute decompensated heart failure (ADHF). Venous waveforms were captured from a peripheral intravenous catheter in subjects admitted for ADHF and healthy age-matched controls. Admission PIVA signal, brain natriuretic peptide, and chest radiographic measurements were related to the net volume removed during diuresis. ADHF patients had a significantly greater PIVA signal on admission compared to the control group (P=0.0013, n=18). At discharge, ADHF patients had a PIVA signal similar to the control group. PIVA signal, not BNP or chest radiographic measures, accurately predicted the amount of volume removed during diuresis (R 2 =0.781, n=14). PIVA signal at time of discharge greater than 0.20, demonstrated 83.3% 120-day readmission rate. This study demonstrates the feasibility of PIVA for assessment of volume overload in patients admitted to the hospital with ADHF. Copyright © 2018. Published by Elsevier Inc.

Right and Left Ventricular Function and Mass in Male Elite Master Athletes: A Controlled Contrast-Enhanced Cardiovascular Magnetic Resonance Study.

PubMed

Bohm, Philipp; Schneider, Günther; Linneweber, Lutz; Rentzsch, Axel; Krämer, Nadine; Abdul-Khaliq, Hashim; Kindermann, Wilfried; Meyer, Tim; Scharhag, Jürgen

2016-05-17

It is under debate whether the cumulative effects of intensive endurance exercise induce chronic cardiac damage, mainly involving the right heart. The aim of this study was to examine the cardiac structure and function in long-term elite master endurance athletes with special focus on the right ventricle by contrast-enhanced cardiovascular magnetic resonance. Thirty-three healthy white competitive elite male master endurance athletes (age range, 30-60 years) with a training history of 29±8 years, and 33 white control subjects pair-matched for age, height, and weight underwent cardiopulmonary exercise testing, echocardiography including tissue-Doppler imaging and speckle tracking, and cardiovascular magnetic resonance. Indexed left ventricular mass and right ventricular mass (left ventricular mass/body surface area, 96±13 and 62±10 g/m(2); P<0.001; right ventricular mass/body surface area, 36±7 and 24±5 g/m(2); P<0.001) and indexed left ventricular end-diastolic volume and right ventricular end-diastolic volume (left ventricular end-diastolic volume/body surface area, 104±13 and 69±18 mL/m(2); P<0.001; right ventricular end-diastolic volume/body surface area, 110±22 and 66±16 mL/m(2); P<0.001) were significantly increased in athletes in comparison with control subjects. Right ventricular ejection fraction did not differ between athletes and control subjects (52±8 and 54±6%; P=0.26). Pathological late enhancement was detected in 1 athlete. No correlations were found for left ventricular and right ventricular volumes and ejection fraction with N-terminal pro-brain natriuretic peptide, and high-sensitive troponin was negative in all subjects. Based on our results, chronic right ventricular damage in elite endurance master athletes with lifelong high training volumes seems to be unlikely. Thus, the hypothesis of an exercise-induced arrhythmogenic right ventricular cardiomyopathy has to be questioned. © 2016 American Heart Association, Inc.

Effect of inhibition of glycogen synthase kinase-3 on cardiac hypertrophy during acute pressure overload.

PubMed

Tateishi, Atsushi; Matsushita, Masayuki; Asai, Tomohiro; Masuda, Zenichi; Kuriyama, Mitsuhito; Kanki, Kazushige; Ishino, Kozo; Kawada, Masaaki; Sano, Shunji; Matsui, Hideki

2010-06-01

A large number of diverse signaling molecules in cell and animal models participate in the stimulus-response pathway through which the hypertrophic growth of the myocardium is controlled. However, the mechanisms of signaling pathway including the influence of lithium, which is known as an inhibitor of glycogen synthase kinase-3beta, in pressure overload hypertrophy remain unclear. The aim of our study was to determine whether glycogen synthase kinase-3beta inhibition by lithium has acute effects on the myocyte growth mechanism in a pressure overload rat model. First, we created a rat model of acute pressure overload cardiac hypertrophy by abdominal aortic banding. Protein expression time courses for beta-catenin, glycogen synthase kinase-3beta, and phosphoserine9-glycogen synthase kinase-3beta were then examined. The rats were divided into four groups: normal rats with or without lithium administration and pressure-overloaded rats with or without lithium administration. Two days after surgery, Western blot analysis of beta-catenin, echo-cardiographic evaluation, left ventricular (LV) weight, and LV atrial natriuretic peptide mRNA levels were evaluated. We observed an increase in the level of glycogen synthase kinase-3beta phosphorylation on Ser 9. A significant enhancement of LV heart weight (P < 0.05) and interventricular septum and posterior wall thickness (P < 0.05) with pressure-overloaded hypertrophy in animals treated with lithium were also observed. Atrial natriuretic peptide mRNA levels were significantly increased with pressure overload hypertrophy in animals treated with lithium. We have shown in an animal model that inhibition of glycogen synthase kinase-3beta by lithium has an additive effect on pressure overload cardiac hypertrophy.

Role of electrocardiographic changes in discriminating acute or chronic right ventricular pressure overload.

PubMed

Can, Mehmet Mustafa; Özveren, Olcay; Biteker, Murat; Şengül, Cihan; Uz, Ömer; Işılak, Zafer; Kırılmaz, Ata

2013-06-01

Pulmonary embolism (PE) and severe pulmonary stenosis (PS) are two distinct conditions accompanied by increased pressure load of the right ventricle (RV). Despite major advances in our understanding of the mechanisms of RV adaptation to the increased pressure, substantial gaps in our knowledge remain unsettled. One of much less known aspect of pressure overload of RV is its impact on electrocardiographic (ECG) changes. In this study, we aimed to study whether acute and chronic RV overload are accompanied by different ECG patterns. Thirty-eight patients with PE underwent ECG monitoring were compared with 20 matched patients with PS in this observational retrospective study. ECG abnormalities suggestive of RV overload were recorded and analyzed in both groups. Logistic regression analysis was used to define the predictors of chronic RV overload. Among the ECG changes studied, premature atrial contraction (OR-12.2, 95% CI, 1.3-107, p=0.008), right axis deviation (OR-20.4, 95% CI 4.2-98, p<0.001), indeterminate axis (OR-0.11, 95% CI 0.02-0.44, p=0.001 0.11), incomplete right bundle branch block (OR-4.2, 95% CI, 1.1-15.4, p=0.02), late R in aVR (OR-8.4, 95% CI 2.1-33.2, p=0.001), qR in V1 lead (OR-8.3, 95% CI 1.2-74.8, p=0.03) were found to be the independent predictors of chronic RV pressure overload. Our data indicate that the ECG changes that attributed to the acute RV pressure loading states may be more prevalent in chronic RV overload as compared with acute RV overload.

The role of adenosine in preconditioning by brief pressure overload in rats.

PubMed

Huang, Cheng-Hsiung; Tsai, Shen-Kou; Chiang, Shu-Chiung; Lai, Chang-Chi; Weng, Zen-Chung

2015-08-01

Brief pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits has been previously reported. Its effects in other species are not known. This study investigates effects of pressure overload and the role of adenosine in rats in this study. MI was induced by 40-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion. MI size was determined by triphenyl tetrazolium chloride staining. Brief pressure overload was induced by two 10-minute episodes of partial snaring of the ascending aorta. Systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. The MI size (mean ± standard deviation), expressed as percentage of area at risk, was significantly reduced in the pressure overload group as well as in the ischemic preconditioning group (17.4 ± 3.0% and 18.2 ± 1.5% vs. 26.6 ± 2.4% in the control group, p < 0.001). Pretreatment with 8-(p-sulfophenyl)-theophylline (SPT), an inhibitor of adenosine receptors, did not significantly limit the protection by pressure overload and ischemic preconditioning (18.3 ± 1.5% and 18.2 ± 2.0%, respectively, p < 0.001). SPT itself did not affect the extent of infarct (25.4 ± 2.0%). The hemodynamics, area at risk and mortality were not significantly different among all groups of animals. Brief pressure overload of the left ventricle preconditioned rat myocardium against infarction. Because SPT did not significantly alter MI size reduction, our results did not support a role of adenosine in preconditioning by pressure overload in rats. Copyright © 2013. Published by Elsevier B.V.

Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS

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

Dhainaut, J.F.; Devaux, J.Y.; Monsallier, J.F.

1986-07-01

Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes weremore » then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H/sub 2/O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H/sub 2/O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.« less

Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

PubMed

Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

2017-12-01

To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia.

PubMed

Horga, Guillermo; Bernacer, Javier; Dusi, Nicola; Entis, Jonathan; Chu, Kingwai; Hazlett, Erin A; Haznedar, M Mehmet; Kemether, Eileen; Byne, William; Buchsbaum, Monte S

2011-10-01

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance.

PubMed

Kim, Jiwon; Medicherla, Chaitanya B; Ma, Claudia L; Feher, Attila; Kukar, Nina; Geevarghese, Alexi; Goyal, Parag; Horn, Evelyn; Devereux, Richard B; Weinsaft, Jonathan W

2016-01-01

Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5 ± 3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34 ± 10 vs. 39 ± 9%; p = 0.01) but similar LVEF (40 ± 21 vs. 39 ± 18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17 ± 7 vs. 12 ± 6 kPa; p < 0.001) corresponding to increased RV end-systolic volume (143 ± 79 vs. 110 ± 36 ml; p = 0.006), myocardial mass (60 ± 21 vs. 53 ± 17 gm; p = 0.04), and PASP (52 ± 18 vs. 41 ± 18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04-1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14-1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69-1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001). Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.

[Corrected transposition of the great arteries].

PubMed

Alva-Espinosa, Carlos

2016-01-01

Corrected transposition of the great arteries is one of the most fascinating entities in congenital heart disease. The apparent corrected condition is only temporal. Over time, most patients develop systemic heart failure, even in the absence of associated lesions. With current imaging studies, precise visualization is achieved in each case though the treatment strategy remains unresolved. In asymptomatic patients or cases without associated lesions, focalized follow-up to assess systemic ventricular function and the degree of tricuspid valve regurgitation is important. In cases with normal ventricular function and mild tricuspid failure, it seems unreasonable to intervene surgically. In patients with significant associated lesions, surgery is indicated. In the long term, the traditional approach may not help tricuspid regurgitation and systemic ventricular failure. Anatomical correction is the proposed alternative to ease the right ventricle overload and to restore the systemic left ventricular function. However, this is a prolonged operation and not without risks and long-term complications. In this review the clinical, diagnostic, and therapeutic aspects are overviewed in the light of the most significant and recent literature.

Is there a place for intra-aortic balloon counterpulsation support in acute right ventricular failure by pressure-overload?

PubMed

Vanden Eynden, Frederic; Mets, Gilles; De Somer, Filip; Bouchez, Stefaan; Bove, Thierry

2015-10-15

Most therapeutic strategies for acute right ventricular failure (RVF) by pressure-overload are directed to improve cardiac output and coronary perfusion pressure by vasopressive agents. The eventual role of intra-aortic balloon counterpulsation (IABP) support remains questionable. This study investigates the contribution of IABP for acute RVF by pressure-overload, in comparison with phenylephrine (PE) and norepinephrine (NOR). Acute RVF is induced by fixed pulmonary artery constriction in 6 pigs, pursuing a 50% reduction of cardiac output. Assessment of the treatment interventions included biventricular PV-loop analysis, and continuous measurement of aortic and right coronary artery flow. Restoration of baseline cardiac output was only observed by administration of NOR (Baseline=3.82±1.52ml/min - RVF=2.03±0.59ml/min - IABP=2.45±0.62ml/min - PE=2.98±0.63ml/min - NOR=3.95±0.73ml/min, p<0.001). NOR had most effect on biventricular contractility (PRSW-slope-RV: IABP +24% - PE +59% - NOR +208%, p<0.001 and PRSW-slope-LV: IABP +36% - PE +53% - NOR +196%, p<0.001), heart rate acceleration (IABP +7% - PE +12% - NOR +51%, p<0.001), and RCA flow (IABP +31% - PE +58% - NOR +180%, p<0.001), concomitant to a higher increase of LV-to-RV pressure ratio (IABP: +7% versus -3%, PE: +36% versus +8%, NOR: +101% versus 42%). The hemodynamic contribution of IABP was limited, unless a modest improvement of LV compliance during PE and NOR infusion. In a model of acute pressure-overload RV failure, IABP appears to offer limited hemodynamic benefit. The administration of norepinephrine is most effective to correct systemic output and myocardial perfusion through adding an inotropic and chronotropic effect to systemic vasopression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy and Safety of Renal Sympathetic Denervation on Dogs with Pressure Overload-Induced Heart Failure.

PubMed

Chen, Pingan; Leng, Shuilong; Luo, Yishan; Li, Shaonan; Huang, Zicheng; Liu, Zhenxi; Liu, Zhen; Wang, Jie; Lei, Xiaoming

2017-02-01

In dogs with heart failure (HF) induced by overload pressure, the role of renal sympathetic denervation (RSD) on heart failure and in the renal artery is unclear. Therefore, we investigated the efficacy and safety of RSD in dogs with pressure overload-induced heart failure. Twenty mongrel dogs were divided into a sham-operated group, an HF group and an HF + RSD group. In the sham-operated group, the abdominal aorta was located but was not constricted, in the HF group, the abdominal aorta was constricted without RSD, and the HF+RSD group underwent RSD with constriction of the abdominal aorta after 10 weeks. Blood sampling assays, echocardiography, intravascular ultrasound (IVUS) measurement and histopathological examination were performed. Renal sympathetic denervation caused a significant reduction in the levels of noradrenaline (166.62±6.84 vs. 183.48±13.66 pg/ml, P<0.05), plasma renin activity (1.93±0.12 vs. 2.10±0.13 ng/mlh, P<0.05) and B-type natriuretic peptide (71.14±3.86 vs. 83.15±5.73 pg/ml, P<0.05) at eight weeks after RSD in the HF+RSD group. Compared with the HF group at eight weeks, the left ventricular internal dimension at end-diastole and end-systole were lower and the left ventricular ejection fraction was higher (all P<0.05) at eight weeks after RSD in the HF+RSD group. Intravenous ultrasound images showed no changes in the renal artery lumen, and intimal hyperplasia and vascular lumen stenosis were not observed after RSD. Renal sympathetic denervation could improve cardiac function in dogs with HF induced by pressure overload; RSD had no adverse influence on the renal artery. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

A new electric method for non-invasive continuous monitoring of stroke volume and ventricular volume-time curves

PubMed Central

2012-01-01

Background In this paper a new non-invasive, operator-free, continuous ventricular stroke volume monitoring device (Hemodynamic Cardiac Profiler, HCP) is presented, that measures the average stroke volume (SV) for each period of 20 seconds, as well as ventricular volume-time curves for each cardiac cycle, using a new electric method (Ventricular Field Recognition) with six independent electrode pairs distributed over the frontal thoracic skin. In contrast to existing non-invasive electric methods, our method does not use the algorithms of impedance or bioreactance cardiography. Instead, our method is based on specific 2D spatial patterns on the thoracic skin, representing the distribution, over the thorax, of changes in the applied current field caused by cardiac volume changes during the cardiac cycle. Since total heart volume variation during the cardiac cycle is a poor indicator for ventricular stroke volume, our HCP separates atrial filling effects from ventricular filling effects, and retrieves the volume changes of only the ventricles. Methods ex-vivo experiments on a post-mortem human heart have been performed to measure the effects of increasing the blood volume inside the ventricles in isolation, leaving the atrial volume invariant (which can not be done in-vivo). These effects have been measured as a specific 2D pattern of voltage changes on the thoracic skin. Furthermore, a working prototype of the HCP has been developed that uses these ex-vivo results in an algorithm to decompose voltage changes, that were measured in-vivo by the HCP on the thoracic skin of a human volunteer, into an atrial component and a ventricular component, in almost real-time (with a delay of maximally 39 seconds). The HCP prototype has been tested in-vivo on 7 human volunteers, using G-suit inflation and deflation to provoke stroke volume changes, and LVot Doppler as a reference technique. Results The ex-vivo measurements showed that ventricular filling caused a pattern over the thorax quite distinct from that of atrial filling. The in-vivo tests of the HCP with LVot Doppler resulted in a Pearson’s correlation of R = 0.892, and Bland-Altman plotting of SV yielded a mean bias of -1.6 ml and 2SD =14.8 ml. Conclusions The results indicate that the HCP was able to track the changes in ventricular stroke volume reliably. Furthermore, the HCP produced ventricular volume-time curves that were consistent with the literature, and may be a diagnostic tool as well. PMID:22900831

[Measurement of left atrial and ventricular volumes in real-time 3D echocardiography. Validation by nuclear magnetic resonance

NASA Technical Reports Server (NTRS)

Bauer, F.; Shiota, T.; Qin, J. X.; White, R. D.; Thomas, J. D.

2001-01-01

The measurement of the left ventricular ejection fraction is important for the evaluation of cardiomyopathy and depends on the measurement of left ventricular volumes. There are no existing conventional echocardiographic means of measuring the true left atrial and ventricular volumes without mathematical approximations. The aim of this study was to test anew real time 3-dimensional echocardiographic system of calculating left atrial and ventricular volumes in 40 patients after in vitro validation. The volumes of the left atrium and ventricle acquired from real time 3-D echocardiography in the apical view, were calculated in 7 sections parallel to the surface of the probe and compared with atrial (10 patients) and ventricular (30 patients) volumes calculated by nuclear magnetic resonance with the simpson method and with volumes of water in balloons placed in a cistern. Linear regression analysis showed an excellent correlation between the real volume of water in the balloons and volumes given in real time 3-dimensional echocardiography (y = 0.94x + 5.5, r = 0.99, p < 0.001, D = -10 +/- 4.5 ml). A good correlation was observed between real time 3-dimensional echocardiography and nuclear magnetic resonance for the measurement of left atrial and ventricular volumes (y = 0.95x - 10, r = 0.91, p < 0.001, D = -14.8 +/- 19.5 ml and y = 0.87x + 10, r = 0.98, P < 0.001, D = -8.3 +/- 18.7 ml, respectively. The authors conclude that real time three-dimensional echocardiography allows accurate measurement of left heart volumes underlying the clinical potential of this new 3-D method.

Effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy: pressure-volume analysis with a nonimaging scintillation probe.

PubMed

Bonow, R O; Ostrow, H G; Rosing, D R; Cannon, R O; Lipson, L C; Maron, B J; Kent, K M; Bacharach, S L; Green, M V

1983-11-01

To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0.17 to 0.72 mg/kg). Percent change in radionuclide stroke counts after verapamil correlated well with percent change in thermodilution stroke volume (r = .87), and changes in diastolic and systolic counts were used to assess relative changes in left ventricular volumes after verapamil. Verapamil produced dose-related increases in end-diastolic counts (19 +/- 9% increase; p less than .001), end-systolic counts (91 +/- 54% increase; p less than .001), and stroke counts (7 +/- 10% increase; p less than .02). This was associated with a decrease in ejection fraction (83 +/- 8% control, 73 +/- 10% verapamil; p less than .001) and, in the 10 patients with left ventricular outflow tract gradients, a reduction in gradient (62 +/- 27 mm Hg control, 32 +/- 35 mm Hg verapamil; p less than .01). The end-systolic pressure-volume relation was shifted downward and rightward in all patients, suggesting a negative inotropic effect. In 10 patients, left ventricular pressure-volume loops were constructed with simultaneous micromanometer pressure recordings and the radionuclide time-activity curve. In five patients, verapamil shifted the diastolic pressure-volume curve downward and rightward, demonstrating improved pressure-volume relations despite the negative inotropic effect, and also increased the peak rate of rapid diastolic filling. In the other five patients, the diastolic pressure-volume relation was unaltered by verapamil, and increased end-diastolic volumes occurred at higher end-diastolic pressures; in these patients, the peak rate of left ventricular diastolic filling was not changed by verapamil. The negative inotropic effects of intravenous verapamil are potentially beneficial in patients with hypertrophic cardiomyopathy by decreasing left ventricular contractile function and increasing left ventricular volume. Verapamil also enhances left ventricular diastolic filling and improves diastolic pressure-volume relations in some patients despite its negative inotropic effect.

Right and left ventricular volumes in vitro by a new nongeometric method

NASA Technical Reports Server (NTRS)

Buckey, J. C.; Beattie, J. M.; Nixon, J. V.; Gaffney, F. A.; Blomqvist, C. G.

1987-01-01

We present an evaluation of a new nongeometric technique for calculating right and left ventricular volumes. This method calculates ventricular chamber volumes from multiple cross-sectional echocardiographic views taken from a single point as the echo beam is tilted progressively through the ventricle. Right and left ventricular volumes are calculated from both the approximate short axis and approximate apical position on 20 in vitro human hearts and compared with the actual chamber volumes. The results for both ventricles from both positions are excellent. Correlation coefficients are > 0.95 for all positions; the standard errors are in the range of 5 to 7 mL and the slopes and intercepts for the regression lines are not significantly different from 1 and 0, respectively (except for the left ventricular short-axis intercept). For all positions, approximately 6 to 8 views are needed for peak accuracy (7.5 degrees to 10 degrees separation). This approach offers several advantages. No geometric assumptions about ventricular shape are made. All images are acquired from a single point (or window), and the digitized points can be used to make a three-dimensional reconstruction of the ventricle. Also, during the calculations a volume distribution curve for the ventricle is produced. The shape of this curve can be characteristic for certain situations (ie, right ventricle, short axis) and can be used to make new simple equations for calculating volume. We conclude that this is an accurate nongeometric method for determining both right and left ventricular volumes in vitro.

Role of Copper and Homocysteine in Pressure Overload Heart Failure

PubMed Central

Hughes, William M.; Rodriguez, Walter E.; Rosenberger, Dorothea; Chen, Jing; Sen, Utpal; Tyagi, Neetu; Moshal, Karni S.; Vacek, Thomas; Kang, Y. James

2009-01-01

Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart. PMID:18679830

Race differences in ventricular remodeling and function among college football players.

PubMed

Haddad, Francois; Peter, Shanon; Hulme, Olivia; Liang, David; Schnittger, Ingela; Puryear, Josephine; Gomari, Fatemeh A; Finocchiaro, Gherardo; Myers, Jonathan; Froelicher, Victor; Garza, Daniel; Ashley, Euan A

2013-07-01

Athletic training is associated with increases in ventricular mass and volume. Recent studies have shown that left ventricular mass increases proportionally in white athletes with a mass/volume ratio approaching unity. The objective of this study was to compare the proportionality in ventricular remodeling and ventricular function in black versus white National Collegiate Athletic Association Division I football players. From 2008 to 2011, football players at Stanford University underwent cardiovascular screening with a 12-point history and physical examination, electrocardiography, and focused echocardiography. Compared with white players, black players had on average higher left ventricular mass indexes (77 ± 11 vs 71 ± 11 g/m(2), p = 0.009), higher mass/volume ratios (1.18 ± 0.16 vs 1.06 ± 0.09 g/ml, p <0.001), and higher QRS vector magnitudes (3.2 ± 0.7 vs 2.7 ± 0.8, p = 0.002). Black race had an odds ratio of 14 (95% confidence interval 5 to 42, p <0.001) for a mass/volume ratio >1.2. Mass/volume ratio was inversely related to early diastolic tissue Doppler velocity e' (r = -0.50, p <0.001) but not to QRS vector magnitude (r = 0.065, p = 0.034). With regard to systolic indexes, there was no significant difference in the left ventricular ejection fraction, velocity of circumferential shortening, and isovolumic acceleration. In conclusion, black college football players exhibit more concentric ventricular remodeling, lower early diastolic annular velocities, and increased ventricular voltage compared with white players. Ventricular mass increases proportionally to volume in white players but not in black players. Copyright © 2013 Elsevier Inc. All rights reserved.

Ventricular distension and diastolic coronary blood flow in the anaesthetized dog.

PubMed

Gattullo, D; Linden, R J; Losano, G; Pagliaro, P; Westerhof, N

1993-01-01

There appears to be no agreement as to whether or not an increase in diastolic left ventricular pressure and/or volume can cause a decrease in diastolic coronary blood flow. We investigated the problem in the anaesthetized dog using a flaccid freely distensible latex balloon inserted into the left ventricle with the animal on extracorporeal circulation and the coronary perfusion pressure constant at about 45 mm Hg. Maximal vasodilatation and suppression of autoregulation in coronary vasculature was obtained by the intracoronary infusion of dipyridamole (10-40 mg/h). Ventricular volume was changed in steps of 10 ml from 10 to 70 ml and back to 10 ml, whilst recording coronary blood flow and left ventricular pressure in the left circumflex coronary artery. Over a range of ventricular volumes from 20 to 50 ml and a concomitant rise in diastolic ventricular pressure to about 20 mm Hg there was no change in the diastolic coronary flow. Only when the ventricular volume was more than two times the control value (i.e. exceeded 50 ml) and left ventricular pressure was more than 20 mm Hg, was there a decrease in coronary flow. During the return of the volume to the control level there was a fall in diastolic flow and ventricular contractility with respect to the values obtained when the volume was increased; these two effects were transient lasting less than 10 min. It was not considered that any of the three models of the coronary circulation, waterfall, intramyocardial pump or varying elastance model could explain our results.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular function during lower body negative pressure

NASA Technical Reports Server (NTRS)

Ahmad, M.; Blomqvist, C. G.; Mullins, C. B.; Willerson, J. T.

1977-01-01

The response of the human left ventricle to lower body negative pressure (LBNP) and the relation between left ventricular function and hemodynamic response were investigated. Ventricular function curves relating stroke volume to end-diastolic volume were obtained in 12 normal men. Volume data were derived from echocardiographic measurements of left ventricular end-systolic and end-diastolic diameters at rest and during lower body negative pressure (LBNP) at minus 40 mm Hg. End-diastolic volume decreased by 19% and stroke volume by 22%. There were no significant changes in heart rate, arterial blood pressure, or end-systolic volume. Thus, moderate levels of LBNP significantly reduce preload and stroke volume without affecting contractile state. The absence of significant changes in heart rate and arterial blood pressure in the presence of a significant reduction in stroke volume is consistent with an increase in systemic peripheral resistance mediated by low-pressure baroreceptors.

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

PubMed Central

Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

2015-01-01

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

Extracellular signal-regulated kinase (ERK) activation preserves cardiac function in pressure overload induced hypertrophy.

PubMed

Mutlak, Michael; Schlesinger-Laufer, Michal; Haas, Tali; Shofti, Rona; Ballan, Nimer; Lewis, Yair E; Zuler, Mor; Zohar, Yaniv; Caspi, Lilac H; Kehat, Izhak

2018-05-24

Chronic pressure overload and a variety of mediators induce concentric cardiac hypertrophy. When prolonged, cardiac hypertrophy culminates in decreased myocardial function and heart failure. Activation of the extracellular signal-regulated kinase (ERK) is consistently observed in animal models of hypertrophy and in human patients, but its role in the process is controversial. We generated transgenic mouse lines with cardiomyocyte restricted overexpression of intrinsically active ERK1, which similar to the observations in hypertrophy is phosphorylated on both the TEY and the Thr207 motifs and is overexpressed at pathophysiological levels. The activated ERK1 transgenic mice developed a modest adaptive hypertrophy with increased contractile function and without fibrosis. Following induction of pressure-overload, where multiple pathways are stimulated, this activation did not further increase the degree of hypertrophy but protected the heart through a decrease in the degree of fibrosis and maintenance of ventricular contractile function. The ERK pathway acts to promote a compensated hypertrophic response, with enhanced contractile function and reduced fibrosis. The activation of this pathway may be a therapeutic strategy to preserve contractile function when the pressure overload cannot be easily alleviated. The inhibition of this pathway, which is increasingly being used for cancer therapy on the other hand, should be used with caution in the presence of pressure-overload. Copyright © 2017. Published by Elsevier B.V.

Sleep-Disordered Breathing in Patients with Pulmonary Valve Incompetence Complicating Congenital Heart Disease.

PubMed

Miles, Susan; Ahmad, Waheed; Bailey, Amy; Hatton, Rachael; Boyle, Andrew; Collins, Nicholas

2016-12-01

Long standing pulmonary regurgitation results in deleterious effects on right heart size and function with late consequences of right heart volume overload including ventricular dilatation, propensity to arrhythmia and right heart failure. As sleep disordered breathing may predispose to elevations in pulmonary vascular resistance and associated negative effects on right ventricular function, we sought to assess this in patients with underlying congenital heart disease. We performed a pilot study to evaluate the incidence of sleep-disordered breathing in a patient population with a history of long standing pulmonary valve incompetence in patients with congenital heart disease using overnight oximetry. Patients with a background of tetralogy of Fallot repair or residual pulmonary incompetence following previous pulmonary valve intervention for congenital pulmonary stenosis were included. Twenty-two patients underwent overnight oximetry. The mean age of the cohort was 34.3 ± 15.2 years with no patients observed to have severe underlying pulmonary hypertension. Abnormal overnight oximetry was seen in 13/22 patients (59.1%) with 2/22 (9.1%) patients considered to have severe abnormalities. An important proportion of patients with a background of pulmonary incompetence complicating congenital heart disease are prone to the development of sleep-disordered breathing as assessed by overnight oximetry. Further study into the prevalence and mechanisms of sleep-disordered breathing in a larger cohort are warranted. © 2016 Wiley Periodicals, Inc.

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.

miR-21 is associated with fibrosis and right ventricular failure

PubMed Central

Hu, Dong-Qing; Zhao, Mingming; Blay, Eddie; Sandeep, Nefthi; Ong, Sang-Ging; Jung, Gwanghyun; Kooiker, Kristina B.; Coronado, Michael; Fajardo, Giovanni; Bernstein, Daniel

2017-01-01

Combined pulmonary insufficiency (PI) and stenosis (PS) is a common long-term sequela after repair of many forms of congenital heart disease, causing progressive right ventricular (RV) dilation and failure. Little is known of the mechanisms underlying this combination of preload and afterload stressors. We developed a murine model of PI and PS (PI+PS) to identify clinically relevant pathways and biomarkers of disease progression. Diastolic dysfunction was induced (restrictive RV filling, elevated RV end-diastolic pressures) at 1 month after generation of PI+PS and progressed to systolic dysfunction (decreased RV shortening) by 3 months. RV fibrosis progressed from 1 month (4.4% ± 0.4%) to 3 months (9.2% ± 1%), along with TGF-β signaling and tissue expression of profibrotic miR-21. Although plasma miR-21 was upregulated with diastolic dysfunction, it was downregulated with the onset of systolic dysfunction), correlating with RV fibrosis. Plasma miR-21 in children with PI+PS followed a similar pattern. A model of combined RV volume and pressure overload recapitulates the evolution of RV failure unique to patients with prior RV outflow tract surgery. This progression was characterized by enhanced TGF-β and miR-21 signaling. miR-21 may serve as a plasma biomarker of RV failure, with decreased expression heralding the need for valve replacement. PMID:28469078

Acquired heart block: a possible complication of patent ductus arteriosus in a preterm infant.

PubMed

Grasser, Monika; Döhlemann, Christoph; Mittal, Rashmi; Till, Holger; Dietz, Hans-Georg; Münch, Georg; Holzinger, Andreas

2008-01-01

A large patent ductus arteriosus (PDA) is a frequently encountered clinical problem in extremely low birth weight (ELBW) infants. It leads to an increased pulmonary blood flow and in a decreased or reversed diastolic flow in the systemic circulation, resulting in complications. Here we report a possible complication of PDA not previously published. On day 8 of life, a male ELBW infant (birth weight 650 g) born at a gestational age of 23 weeks and 3 days developed an atrioventricular block (AV block). The heart rate dropped from 168/min to 90/min, and the ECG showed a Wenckebach second-degree AV block and intraventricular conduction disturbances. Echocardiography demonstrated a PDA with a large left-to-right shunt and large left atrium and left ventricle with high contractility. Within several minutes after surgical closure of the PDA, the heart rate increased, and after 30 min the AV block had improved to a 1:1 conduction ratio. Echocardiography after 2 h revealed a significant decrease of the left ventricular and atrial dimensions. Within 12 h, the AV block completely reversed together with the intraventricular conduction disturbances. We suggest that PDA with a large left-to-right shunt and left ventricular volume overload may lead to an AV block in an ELBW infant. Surgical closure of the PDA may be indicated. (c) 2007 S. Karger AG, Basel.

The effect of fluid overload on sleep apnoea severity in haemodialysis patients.

PubMed

Lyons, Owen D; Inami, Toru; Perger, Elisa; Yadollahi, Azadeh; Chan, Christopher T; Bradley, T Douglas

2017-04-01

As in heart failure, obstructive and central sleep apnoea (OSA and CSA, respectively) are common in end-stage renal disease. Fluid overload characterises end-stage renal disease and heart failure, and in heart failure plays a role in the pathogenesis of OSA and CSA. We postulated that in end-stage renal disease patients, those with sleep apnoea would have greater fluid volume overload than those without.End-stage renal disease patients on thrice-weekly haemodialysis underwent overnight polysomnography on a nondialysis day to determine their apnoea-hypopnoea index (AHI). Extracellular fluid volume of the total body, neck, thorax and right leg were measured using bioelectrical impedance.28 patients had an AHI ≥15 (sleep apnoea group; OSA:CSA 21:7) and 12 had an AHI <15 (no sleep apnoea group). Total body extracellular fluid volume was 2.6 L greater in the sleep apnoea group than in the no sleep apnoea group (p=0.006). Neck, thorax, and leg fluid volumes were also greater in the sleep apnoea than the no sleep apnoea group (p<0.05), despite no difference in body mass index (p=0.165).These findings support a role for fluid overload in the pathogenesis of both OSA and CSA in end-stage renal disease. Copyright ©ERS 2017.

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.

Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock

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

Ognibene, F.P.; Parker, M.M.; Natanson, C.

Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery catheter hemodynamic measurements and radionuclide cineangiography. Critically ill control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic measurements determined and received statistically similar volumes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was amore » strong trend (p = 0.004) toward less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically ill control subjects (p less than 0.05). These data demonstrate significantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock.« less

Additional mechanism for left ventricular dysfunction: chronic pulmonary regurgitation decreases left ventricular preload in patients with tetralogy of Fallot.

PubMed

Ylitalo, Pekka; Jokinen, Eero; Lauerma, Kirsi; Holmström, Miia; Pitkänen-Argillander, Olli M

2018-02-01

Right ventricular dysfunction in patients with tetralogy of Fallot and significant pulmonary regurgitation may lead to systolic dysfunction of the left ventricle due to altered ventricular interaction. We were interested in determining whether chronic pulmonary regurgitation affects the preload of the left ventricle. In addition, we wanted to study whether severe chronic pulmonary regurgitation would alter the preload of the left ventricle when compared with patients having preserved pulmonary valve annulus. The study group comprised 38 patients with tetralogy of Fallot who underwent surgical repair between 1990 and 2003. Transannular patching was required in 21 patients to reconstruct the right ventricular outflow tract. Altogether, 48 age- and gender-matched healthy volunteers were recruited. Cardiac MRI was performed on all study patients to assess the atrial and ventricular volumes and function. Severe pulmonary regurgitation (>30 ml/m2) was present in 13 patients, of whom 11 had a transannular patch, but only two had a preserved pulmonary valve annulus. The ventricular preload volumes from both atria were significantly reduced in patients with severe pulmonary regurgitation, and left ventricular stroke volumes (44.1±4.7 versus 58.9±10.7 ml/m2; p<0.0001) were smaller compared with that in patients with pulmonary regurgitation <30 ml/m2 or in controls. In patients with tetralogy of Fallot, severe pulmonary regurgitation has a significant effect on volume flow through the left atrium. Reduction in left ventricular preload volume may be an additional factor contributing to left ventricular dysfunction.

Short Communication: Conformal Therapy for Peri-Ventricular Brain Tumors: Is Target Volume Deformation an Issue?

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

Bauman, Glenn; Woodford, Curtis; Yartsev, Slav

2008-04-01

Physiologic variations in ventricular volumes could have important implications for treating patients with peri-ventricular brain tumors, yet no data exist in the literature addressing this issue. Daily megavoltage computed tomography (CT) scans in a patient with neurocytoma receiving fractionated radiation revealed minimal changes, suggesting that margins accounting for ventricular deformation are not necessary.

[Experts consensus on the management of the right heart function in critically ill patients].

PubMed

Wang, X T; Liu, D W; Zhang, H M; Long, Y; Guan, X D; Qiu, H B; Yu, K J; Yan, J; Zhao, H; Tang, Y Q; Ding, X; Ma, X C; Du, W; Kang, Y; Tang, B; Ai, Y H; He, H W; Chen, D C; Chen, H; Chai, W Z; Zhou, X; Cui, N; Wang, H; Rui, X; Hu, Z J; Li, J G; Xu, Y; Yang, Y; Ouyan, B; Lin, H Y; Li, Y M; Wan, X Y; Yang, R L; Qin, Y Z; Chao, Y G; Xie, Z Y; Sun, R H; He, Z Y; Wang, D F; Huang, Q Q; Jiang, D P; Cao, X Y; Yu, R G; Wang, X; Chen, X K; Wu, J F; Zhang, L N; Yin, M G; Liu, L X; Li, S W; Chen, Z J; Luo, Z

2017-12-01

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

Determination of volume-time curves for the right ventricle and its outflow tract for functional analyses.

PubMed

Gabbert, Dominik D; Entenmann, Andreas; Jerosch-Herold, Michael; Frettlöh, Felicitas; Hart, Christopher; Voges, Inga; Pham, Minh; Andrade, Ana; Pardun, Eileen; Wegner, P; Hansen, Traudel; Kramer, Hans-Heiner; Rickers, Carsten

2013-12-01

The determination of right ventricular volumes and function is of increasing interest for the postoperative care of patients with congenital heart defects. The presentation of volumetry data in terms of volume-time curves allows a comprehensive functional assessment. By using manual contour tracing, the generation of volume-time curves is exceedingly time-consuming. This study describes a fast and precise method for determining volume-time curves for the right ventricle and for the right ventricular outflow tract. The method applies contour detection and includes a feature for identifying the right ventricular outflow tract volume. The segregation of the outflow tract is performed by four-dimensional curved smooth boundary surfaces defined by prespecified anatomical landmarks. The comparison with manual contour tracing demonstrates that the method is accurate and improves the precision of the measurement. Compared to manual contour tracing the bias is <0.1% ± 4.1% (right ventricle) and -2.6% ± 20.0% (right ventricular outflow tract). The standard deviations of inter- and intraobserver variabilities for determining the volume of the right ventricular outflow tract are reduced to less than half the values of manual contour tracing. The time consumption per patient is reduced from 341 ± 80 min (right ventricle) and 56 ± 11 min (right ventricular outflow tract) using manual contour tracing to 46 ± 9 min for a combined analysis of right ventricle and right ventricular outflow tract. The analysis of volume-time curves for the right ventricle and its outflow tract discloses new evaluation methods in clinical routine and science. Copyright © 2013 Wiley Periodicals, Inc.

Origins and consequences of congenital heart defects affecting the right ventricle.

PubMed

Woudstra, Odilia I; Ahuja, Suchit; Bokma, Jouke P; Bouma, Berto J; Mulder, Barbara J M; Christoffels, Vincent M

2017-10-01

Congenital heart disease is a major health issue, accounting for a third of all congenital defects. Improved early surgical management has led to a growing population of adults with congenital heart disease, including patients with defects affecting the right ventricle, which are often classified as severe. Defects affecting the right ventricle often cause right ventricular volume or pressure overload and affected patients are at high risk for complications such as heart failure and sudden death. Recent insights into the developmental mechanisms and distinct developmental origins of the left ventricle, right ventricle, and the outflow tract have shed light on the common features and distinct problems arising in specific defects. Here, we provide a comprehensive overview of the current knowledge on the development into the normal and congenitally malformed right heart and the clinical consequences of several congenital heart defects affecting the right ventricle. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs

PubMed Central

Kamat, Pranitha; Vandenberghe, Stijn; Christen, Stephan; Bongoni, Anjan K.; Meier, Bernhard; Rieben, Robert; Khattab, Ahmed A.

2016-01-01

Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R) injury during myocardial infarction (MI). Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS). We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5) or saline (n = 5) was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group) as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE), endothelial cell activation (CD31) and inflammation (IgG, C3b/c, C5b9, MCP-1) were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters. PMID:28002439

Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy.

PubMed

Desai, Ankit A; Patel, Amit R; Ahmad, Homaa; Groth, John V; Thiruvoipati, Thejasvi; Turner, Kristen; Yodwut, Chattanong; Czobor, Peter; Artz, Nicole; Machado, Roberto F; Garcia, Joe G N; Lang, Roberto M

2014-05-01

Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms. Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m(2)), right ventricle (127±28 vs 83±14 mL/m(2)), left atrium (65±16 vs 41±9 mL/m(2)), and right atrium (78±17 vs 56±17 mL/m(2); P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e', 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all). Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness. http://www.clinicaltrials.gov. Unique identifier: NCT01044901. © 2014 American Heart Association, Inc.

Three-Dimensional Right Ventricular Strain Versus Volume Quantification in Heart Transplant Recipients in Relation to Pulmonary Artery Pressure.

PubMed

Sade, Leyla Elif; Kozan, Hatice; Eroglu, Serpil; Pirat, Bahar; Aydinalp, Alp; Sezgin, Atilla; Muderrisoglu, Haldun

2017-02-01

Residual pulmonary hypertension challenges the right ventricular function and worsens the prognosis in heart transplant recipients. The complex geometry of the right ventricle complicates estimation of its function with conventional transthoracic echocardiography. We evaluated right ventricular function in heart transplant recipients with the use of 3-dimensional echocardiography in relation to systolic pulmonary artery pressure. We performed 32 studies in 26 heart transplant patients, with 6 patients having 2 studies at different time points with different pressures and thus included. Right atrial volume, tricuspid annular plane systolic excursion, peak systolic annular velocity, fractional area change, and 2-dimensional speckle tracking longitudinal strain were obtained by 2-dimensional and tissue Doppler imaging. Three-dimensional right ventricular volumes, ejection fraction, and 3-dimensional right ventricular strain were obtained from the 3-dimensional data set by echocardiographers. Systolic pulmonary artery pressure was obtained during right heart catheterization. Overall mean systolic pulmonary artery pressure was 26 ± 7 mm Hg (range, 14-44 mmHg). Three-dimensional end-diastolic (r = 0.75; P < .001) and end-systolic volumes (r = 0.55; P = .001)correlated well with systolic pulmonary artery pressure. Right ventricular ejection fraction and right atrium volume also significantly correlated with systolic pulmonary artery pressure (r = 0.49 and P = .01 for both). However, right ventricular 2- and 3-dimensional strain, tricuspid annular plane systolic excursion, and tricuspid annular velocity did not. The effects of pulmonary hemodynamic burden on right ventricular function are better estimated by a 3-dimensional volume evaluation than with 3-dimensional longitudinal strain and other 2-dimensional and tissue Doppler measurements. These results suggest that the peculiar anatomy of the right ventricle necessitates 3-dimensional volume quantification in heart transplant recipients in relation to residual pulmonary hypertension.

Targeting focal adhesion kinase with small interfering RNA prevents and reverses load-induced cardiac hypertrophy in mice.

PubMed

Clemente, Carolina F M Z; Tornatore, Thais F; Theizen, Thais H; Deckmann, Ana C; Pereira, Tiago C; Lopes-Cendes, Iscia; Souza, José Roberto M; Franchini, Kleber G

2007-12-07

Hypertrophy is a critical event in the onset of failure in chronically overloaded hearts. Focal adhesion kinase (FAK) has attracted particular attention as a mediator of hypertrophy induced by increased load. Here, we demonstrate increased expression and phosphorylation of FAK in the hypertrophic left ventricles (LVs) of aortic-banded mice. We used an RNA interference strategy to examine whether FAK signaling plays a role in the pathophysiology of load-induced LV hypertrophy and failure. Intrajugular delivery of specific small interfering RNA induced prolonged FAK silencing ( approximately 70%) in both normal and hypertrophic LVs. Myocardial FAK silencing was accompanied by prevention, as well as reversal, of load-induced left ventricular hypertrophy. The function of LVs was preserved and the survival rate was higher in banded mice treated with small interfering RNA targeted to FAK, despite the persistent pressure overload. Studies in cardiac myocytes and fibroblasts harvested from LVs confirmed the ability of the systemically administered specific small interfering RNA to silence FAK in both cell types. Further analysis indicated attenuation of cardiac myocyte hypertrophic growth and of the rise in the expression of beta-myosin heavy chain in overloaded LVs. Moreover, FAK silencing was demonstrated to attenuate the rise in the fibrosis, collagen content, and activity of matrix metalloproteinase-2 in overloaded LVs, as well as the rise of matrix metalloproteinase-2 protein expression in fibroblasts harvested from overloaded LVs. This study provides novel evidence that FAK may be involved in multiple aspects of the pathophysiology of cardiac hypertrophy and failure induced by pressure overload.

Brief pressure overload of the left ventricle reduces myocardial infarct size via activation of protein kinase C.

PubMed

Tang, Chia-Yu; Lai, Chang-Chi; Chiang, Shu-Chiung; Tseng, Kuo-Wei; Huang, Cheng-Hsiung

2015-09-01

We have previously reported that brief pressure overload of the left ventricle reduced myocardial infarct (MI) size. However, the role of protein kinase C (PKC) remains uncertain. In this study, we investigated whether pressure overload reduces MI size by activating PKC. MI was induced by a 40-minute occlusion of the left anterior descending coronary artery and a 3-hour reperfusion in anesthetized Sprague-Dawley rats. MI size was determined using triphenyl tetrazolium chloride staining. Brief pressure overload was achieved by two 10-minute partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and 10-minute reperfusions. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/kg, a specific inhibitor of PKC) was administered intravenously as pretreatment. The MI size, expressed as the percentage of the area at risk, was significantly reduced in the pressure overload group and the ischemic preconditioning group (19.0 ± 2.9% and 18.7 ± 3.0% vs. 26.1 ± 2.6% in the control group, where p < 0.001). Pretreatment with calphostin C significantly limited the protection by pressure overload and ischemic preconditioning (25.2 ± 2.4% and 25.0 ± 2.3%, where p < 0.001). Calphostin C itself did not significantly affect MI size (25.5 ± 2.4%). Additionally, the hemodynamics, area at risk, and mortality were not significantly different. Brief pressure overload of the left ventricle reduced MI size. Since calphostin C significantly limited the decrease of MI size, our results suggested that brief pressure overload reduces MI size via activation of PKC. Copyright © 2015. Published by Elsevier Taiwan.

Left ventricular function before and after kidney transplantation.

PubMed

Omran, Mohammad T; Khakpour, Somayeh; Oliaie, Farshid

2009-06-01

To evaluate left ventricular function by echocardiography before and after kidney transplantation (KT). This analytical study included 50 patients that had successful KT in Shahid Beheshti Hospital, Babol, Iran from October 2005 to December 2007. The echocardiography study was performed by one cardiologist before and at least 3 months after KT. Data were analyzed by SPSS, and a p<0.05 was considered statistically significant. The mean age of patients was 33.94 +/- 11.66 years, 66% were male and 56% less than 45 years old. The ejection fraction and stroke volume after KT increased, however, the left ventricular end diastolic volume, left ventricular end systolic volume, left ventricular end systolic dimension, and left ventricular end diastolic diameter decreased. In patients with end stage renal disease, successful kidney transplantation could improve the function of the left ventricle.

Chronic Ethanol Administration Prevents Compensatory Cardiac Hypertrophy in Pressure Overload.

PubMed

Ninh, Van K; El Hajj, Elia C; Mouton, Alan J; El Hajj, Milad C; Gilpin, Nicholas W; Gardner, Jason D

2018-05-30

Alcohol is among the most commonly abused drugs worldwide and affects many organ systems, including the heart. Alcoholic cardiomyopathy is characterized by a dilated cardiac phenotype with extensive hypertrophy and extracellular matrix (ECM) remodeling. We have previously shown that chronic ethanol (EtOH) administration accelerates the progression to heart failure in a rat model of volume overload. However, the mechanism by which this decompensation occurs is unknown. For this study, we hypothesized that chronic EtOH administration would prevent compensatory hypertrophy and cardiac remodeling in a rodent model of pressure overload (PO). Abdominal aortic constriction was used to create PO in 8-week-old male Wistar rats. Alcohol administration was performed via chronic intermittent EtOH vapor inhalation for 2 weeks prior to surgery and for the duration of the 8-week study. Echocardiography measurements were taken to assess ventricular functional and structural changes. PO increased posterior wall thickness and the hypertrophic markers, atrial and B-type natriuretic peptides (ANP and BNP). With the added stressor of EtOH, wall thickness, ANP, and BNP decreased in PO animals. The combination of PO and EtOH resulted in increased wall stress compared to PO alone. PO also caused increased expression of collagen I and III, whereas EtOH alone only increased collagen III. The combined stresses of PO and EtOH led to an increase in collagen I expression, but collagen III did not change, resulting in an increased collagen I/III ratio in the PO rats treated with EtOH. Lastly, Notch1 expression was significantly increased only in the PO rats treated with EtOH. Our data indicate that chronic EtOH may limit the cardiac hypertrophy induced by PO which may be associated with a Notch1 mechanism, resulting in increased wall stress and altered ECM profile. Copyright © 2018 by the Research Society on Alcoholism.

Amiodarone inhibits sarcolemmal but not mitochondrial KATP channels in Guinea pig ventricular cells.

PubMed

Sato, Toshiaki; Takizawa, Taichi; Saito, Tomoaki; Kobayashi, Satoru; Hara, Yukio; Nakaya, Haruaki

2003-12-01

ATP-sensitive K(+) (KATP) channels are present on the sarcolemma (sarcKATP channels) and mitochondria (mitoKATP channels) of cardiac myocytes. Amiodarone, a class III antiarrhythmic drug, reduces sudden cardiac death in patients with organic heart disease. The objective of the present study was to investigate the effects of amiodarone on sarcKATP and mitoKATP channels. Single sarcKATP channel current and flavoprotein fluorescence were measured in guinea pig ventricular myocytes to assay sarcKATP and mitoKATP channel activity, respectively. Amiodarone inhibited the sarcKATP channel currents in a concentration-dependent manner without affecting its unitary amplitude. The IC50 values were 0.35 microM in the inside-out patch exposed to an ATP-free solution and 2.8 microM in the cell-attached patch under metabolic inhibition, respectively. Amiodarone (10 microM) alone did not oxidize the flavoprotein. In addition, the oxidative effect of the mitoKATP channel opener diazoxide (100 microM) was unaffected by amiodarone. Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca(2+) overload, and the intensity of rhod-2 fluorescence increased to 246 +/- 16% of baseline (n = 9). Amiodarone did not alter the ouabain-induced mitochondrial Ca(2+) overload (236 +/- 10% of baseline, n = 7). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca(2+) overload (158 +/- 15% of baseline, n = 8, p < 0.05 versus ouabain); this effect was not abolished by amiodarone (154 +/- 10% of baseline, n = 8, p < 0.05 versus ouabain). These results suggest that amiodarone inhibits sarcKATP but not mitoKATP channels in cardiac myocytes. Such an action of amiodarone may effectively prevent ischemic arrhythmias without causing ischemic damage.

Impact of Major Pulmonary Resections on Right Ventricular Function: Early Postoperative Changes.

PubMed

Elrakhawy, Hany M; Alassal, Mohamed A; Shaalan, Ayman M; Awad, Ahmed A; Sayed, Sameh; Saffan, Mohammad M

2018-01-15

Right ventricular (RV) dysfunction after pulmonary resection in the early postoperative period is documented by reduced RV ejection fraction and increased RV end-diastolic volume index. Supraventricular arrhythmia, particularly atrial fibrillation, is common after pulmonary resection. RV assessment can be done by non-invasive methods and/or invasive approaches such as right cardiac catheterization. Incorporation of a rapid response thermistor to pulmonary artery catheter permits continuous measurements of cardiac output, right ventricular ejection fraction, and right ventricular end-diastolic volume. It can also be used for right atrial and right ventricular pacing, and for measuring right-sided pressures, including pulmonary capillary wedge pressure. This study included 178 patients who underwent major pulmonary resections, 36 who underwent pneumonectomy assigned as group (I) and 142 who underwent lobectomy assigned as group (II). The study was conducted at the cardiothoracic surgery department of Benha University hospital in Egypt; patients enrolled were operated on from February 2012 to February 2016. A rapid response thermistor pulmonary artery catheter was inserted via the right internal jugular vein. Preoperatively the following was recorded: central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, right ventricular ejection fraction and volumes. The same parameters were collected in fixed time intervals after 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours postoperatively. For group (I): There were no statistically significant changes between the preoperative and postoperative records in the central venous pressure and mean arterial pressure; there were no statistically significant changes in the preoperative and 12, 24, and 48 hour postoperative records for cardiac index; 3 and 6 hours postoperative showed significant changes. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index, in all postoperative records. For group (II): There were no statistically significant changes between the preoperative and all postoperative records for the central venous pressure, mean arterial pressure and cardiac index. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index in all postoperative records. There were statistically significant changes between the two groups in all postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index. There is right ventricular dysfunction early after major pulmonary resection caused by increased right ventricular afterload. This dysfunction is more present in pneumonectomy than in lobectomy. Heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction, and right ventricular end diastolic volume index are significantly affected by pulmonary resection.

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

PubMed Central

Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

2017-01-01

Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats. PMID:28287621

Viral Vector-Based Targeting of miR-21 in Cardiac Nonmyocyte Cells Reduces Pathologic Remodeling of the Heart

PubMed Central

Ramanujam, Deepak; Sassi, Yassine; Laggerbauer, Bernhard; Engelhardt, Stefan

2016-01-01

Systemic inhibition of miR-21 has proven effective against myocardial fibrosis and dysfunction, while studies in cardiac myocytes suggested a protective role in this cell type. Considering potential implications for therapy, we aimed to determine the cell fraction where miR-21 exerts its pathological activity. We developed a viral vector-based strategy for gene targeting of nonmyocyte cardiac cells in vivo and compared global to cardiac myocyte-specific and nonmyocyte-specific deletion of miR-21 in chronic left ventricular pressure overload. Murine moloney virus and serotype 9 of adeno-associated virus were engineered to encode improved Cre recombinase for genetic deletion in miR-21fl/fl mice. Pericardial injection of murine moloney virus-improved Cre recombinase to neonates achieved highly selective genetic ablation of miR-21 in nonmyocyte cardiac cells, identified as cardiac fibroblasts and endothelial cells. Upon left ventricular pressure overload, cardiac function was only preserved in mice with miR-21 deficiency in nonmyocyte cardiac cells, but not in mice with global or cardiac myocyte-specific ablation. Our data demonstrate that miR-21 exerts its pathologic activity directly in cardiac nonmyocytes and encourage further development of antimiR-21 therapy toward cellular tropism. PMID:27545313

Embryonic cardiac morphometry in Carnegie stages 15-23, from the Complutense University of Madrid Institute of Embryology Human Embryo Collection.

PubMed

Arráez-Aybar, L A; Turrero-Nogués, A; Marantos-Gamarra, D G

2008-01-01

We performed a morphometric study of cardiac development on human embryos to complement the scarce data on human embryonic cardiac morphometry and to attempt to establish, from these, algorithms describing cardiac growth during the second month of gestation. Thirty human embryos from Carnegie stages 15-23 were included in the study. Shrinkage and compression effects from fixation and inclusion in paraffin were considered in our calculations. Growth of the cardiac (whole heart) volume and volume of ventricular myocardium through the Carnegie stages were analysed by ANOVA. Linear correlation was used to describe the relationship between the ventricular myocardium and cardiac volumes. Comparisons of models were carried out through the R2 statistic. The relationship volume of ventricular myocardium versus cardiac volume is expressed by the equation: cardiac volume = 0.6266 + 2.4778 volume of ventricular myocardium. The relationship cardiac volume versus crown-rump length is expressed by the equation: cardiac volume = 1.3 e(0.126 CR length), where e is the base of natural logarithms. At a clinical level, these results can contribute towards the establishment of a normogram for cardiac development, useful for the design of strategies for early diagnosis of congenital heart disease. They can also help in the study of embryogenesis, for example in the discussion of ventricular trabeculation. Copyright 2007 S. Karger AG, Basel.

Knowledge-based reconstruction for measurement of right ventricular volumes on cardiovascular magnetic resonance images in a mixed population.

PubMed

Pieterman, Elise D; Budde, Ricardo P J; Robbers-Visser, Daniëlle; van Domburg, Ron T; Helbing, Willem A

2017-09-01

Follow-up of right ventricular performance is important for patients with congenital heart disease. Cardiac magnetic resonance imaging is optimal for this purpose. However, observer-dependency of manual analysis of right ventricular volumes limit its use. Knowledge-based reconstruction is a new semiautomatic analysis tool that uses a database including knowledge of right ventricular shape in various congenital heart diseases. We evaluated whether knowledge-based reconstruction is a good alternative for conventional analysis. To assess the inter- and intra-observer variability and agreement of knowledge-based versus conventional analysis of magnetic resonance right ventricular volumes, analysis was done by two observers in a mixed group of 22 patients with congenital heart disease affecting right ventricular loading conditions (dextro-transposition of the great arteries and right ventricle to pulmonary artery conduit) and a group of 17 healthy children. We used Bland-Altman analysis and coefficient of variation. Comparison between the conventional method and the knowledge-based method showed a systematically higher volume for the latter group. We found an overestimation for end-diastolic volume (bias -40 ± 24 mL, r = .956), end-systolic volume (bias -34 ± 24 mL, r = .943), stroke volume (bias -6 ± 17 mL, r = .735) and an underestimation of ejection fraction (bias 7 ± 7%, r = .671) by knowledge-based reconstruction. The intra-observer variability of knowledge-based reconstruction varied with a coefficient of variation of 9% for end-diastolic volume and 22% for stroke volume. The same trend was noted for inter-observer variability. A systematic difference (overestimation) was noted for right ventricular size as assessed with knowledge-based reconstruction compared with conventional methods for analysis. Observer variability for the new method was comparable to what has been reported for the right ventricle in children and congenital heart disease with conventional analysis. © 2017 Wiley Periodicals, Inc.

Quantitative Computed Tomography Ventriculography for Assessment and Monitoring of Hydrocephalus: A Pilot Study and Description of Method in Subarachnoid Hemorrhage.

PubMed

Multani, Jasjit Singh; Oermann, Eric Karl; Titano, Joseph; Mascitelli, Justin; Nicol, Kelly; Feng, Rui; Skovrlj, Branko; Pain, Margaret; Mocco, J D; Bederson, Joshua B; Costa, Anthony; Shrivastava, Raj

2017-08-01

There is no facile quantitative method for monitoring hydrocephalus (HCP). We propose quantitative computed tomography (CT) ventriculography (qCTV) as a novel computer vision tool for empirically assessing HCP in patients with subarachnoid hemorrhage (SAH). Twenty patients with SAH who were evaluated for ventriculoperitoneal shunt (VPS) placement were selected for inclusion. Ten patients with normal head computed tomography (CTH) findings were analyzed as negative controls. CTH scans were segmented both manually and automatically (by qCTV) to generate measures of ventricular volume. The median manually calculated ventricular volume was 36.1 cm 3 (interquartile range [IQR], 30-115 cm 3 ), which was similar to the median qCTV measured volume of 37.5 cm 3 (IQR, 32-118 cm 3 ) (P = 0.796). Patients undergoing VPS placement demonstrated an increase in median ventricular volume on qCTV from 21 cm 3 to 40 cm 3 on day T-2 and to 51 cm 3 by day 0, a change of 144%. This is in contrast to patients who did not require shunting, in whom median ventricular volume decreased from 16 cm 3 to 14 cm 3 on day T-2 and to 13 cm 3 by day 0, with an average overall volume decrease 19% (P = 0.001). The average change in ventricular volume predicted which patients would require VPS placement, successfully identifying 7 of 10 patients (P = 0.004). Using an optimized cutoff of a change in ventricular volume of 2.5 cm 3 identified all patients who went on to require VPS placement (10 of 10; P = 0.011). qCTV is a reliable means of quantifying ventricular volume and hydrocephalus. This technique offers a new tool for monitoring neurosurgical patients for hydrocephalus, and may be beneficial for use in future research studies, as well as in the routine care of patients with hydrocephalus. Copyright © 2017 Elsevier Inc. All rights reserved.

Masked hypertension and cardiac remodeling in middle-aged endurance athletes.

PubMed

Trachsel, Lukas D; Carlen, Frederik; Brugger, Nicolas; Seiler, Christian; Wilhelm, Matthias

2015-06-01

Extensive endurance training and arterial hypertension are established risk factors for atrial fibrillation. We aimed to assess the proportion of masked hypertension in endurance athletes and the impact on cardiac remodeling, mechanics, and supraventricular tachycardias (SVT). Male participants of a 10-mile race were recruited and included if office blood pressure was normal (<140/90 mmHg). Athletes were stratified into a masked hypertension and normotension group by ambulatory blood pressure. Primary endpoint was diastolic function, expressed as peak early diastolic mitral annulus velocity (E'). Left ventricular global strain, left ventricular mass/volume ratio, left atrial volume index, signal-averaged P-wave duration (SAPWD), and SVT during 24-h Holter monitoring were recorded. From 108 runners recruited, 87 were included in the final analysis. Thirty-three (38%) had masked hypertension. The mean age was 42 ± 8 years. Groups did not differ with respect to age, body composition, cumulative training hours, and 10-mile race time. Athletes with masked hypertension had a lower E' and a higher left ventricular mass/volume ratio. Left ventricular global strain, left atrial volume index, SAPWD, and SVT showed no significant differences between the groups. In multiple linear regression analysis, masked hypertension was independently associated with E' (beta = -0.270, P = 0.004) and left ventricular mass/volume ratio (beta = 0.206, P = 0.049). Cumulative training hours was the only independent predictor for left atrial volume index (beta = 0.474, P < 0.001) and SAPWD (beta = 0.481, P < 0.001). In our study, a relevant proportion of middle-aged athletes had masked hypertension, associated with a lower diastolic function and a higher left ventricular mass/volume ratio, but unrelated to left ventricular systolic function, atrial remodeling, or SVT.

Two-year analysis of efficacy and safety of deferasirox treatment for transfusional iron overload in sickle cell anemia patients.

PubMed

Cancado, Rodolfo; Olivato, Maria Cristina A; Bruniera, Paula; Szarf, Gilberto; de Moraes Bastos, Roberto; Rezende Melo, Murilo; Chiattone, Carlos

2012-01-01

The efficacy and safety of a 2-year treatment with deferasirox was evaluated in 31 patients with sickle cell anemia and transfusional iron overload. At 24 months, there were significant decreases from baseline in mean serum ferritin (from 2,344.6 to 1,986.3 µg/l; p = 0.040) and in mean liver iron concentration (from 13.0 ± 5.4 to 9.3 ± 5.7 mg Fe/g dry weight; p < 0.001). Myocardial T2* values were normal (>20 ms) in all patients at baseline and did not change significantly over the course of the study. However, there was a significant improvement from baseline in left ventricular ejection fraction at 24 months (62.2-64.6%; p = 0.02). Deferasirox was generally well tolerated with no progressive increases in serum creatinine or renal failure observed. These data confirm that deferasirox is effective in reducing body iron burden in patients with sickle cell anemia and transfusional iron overload. Copyright © 2012 S. Karger AG, Basel.

Genetic Ablation of Fgf23 or Klotho Does not Modulate Experimental Heart Hypertrophy Induced by Pressure Overload.

PubMed

Slavic, Svetlana; Ford, Kristopher; Modert, Magalie; Becirovic, Amarela; Handschuh, Stephan; Baierl, Andreas; Katica, Nejla; Zeitz, Ute; Erben, Reinhold G; Andrukhova, Olena

2017-09-12

Left ventricular hypertrophy (LVH) ultimately leads to heart failure in conditions of increased cardiac pre- or afterload. The bone-derived phosphaturic and sodium-conserving hormone fibroblast growth factor-23 (FGF23) and its co-receptor Klotho have been implicated in the development of uremic LVH. Using transverse aortic constriction (TAC) in gene-targeted mouse models, we examine the role of Fgf23 and Klotho in cardiac hypertrophy and dysfunction induced by pressure overload. TAC profoundly increases serum intact Fgf23 due to increased cardiac and bony Fgf23 transcription and downregulation of Fgf23 cleavage. Aldosterone receptor blocker spironolactone normalizes serum intact Fgf23 levels after TAC by reducing bony Fgf23 transcription. Notably, genetic Fgf23 or Klotho deficiency does not influence TAC-induced hypertrophic remodelling, LV functional impairment, or LV fibrosis. Despite the profound, aldosterone-mediated increase in circulating intact Fgf23 after TAC, our data do not support an essential role of Fgf23 or Klotho in the pathophysiology of pressure overload-induced cardiac hypertrophy.

Transforming growth factor-β inhibits myocardial PPARγ expression in pressure overload-induced cardiac fibrosis and remodeling in mice

PubMed Central

Gong, Kaizheng; Chen, Yiu-Fai; Li, Peng; Lucas, Jason A.; Hage, Fadi G.; Yang, Qinglin; Nozell, Susan E.; Oparil, Suzanne; Xing, Dongqi

2012-01-01

Objectives Pharmacological activation of peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to attenuate pressure overload-induced cardiac fibrosis, suggesting that PPARγ has an antifibrotic effect. This study tested the hypothesis that there is a functional interaction between transforming growth factor-β (TGF-β) signaling and endogenous PPARγ expression in cardiac fibroblasts and pressure overloaded heart. Methods and results We observed that, in response to pressure overload induced by transverse aortic constriction, left-ventricular PPARγ protein levels were decreased in wild-type mice, but increased in mice with an inducible overexpression of dominant negative mutation of the human TGF-β type II receptor (DnTGFβRII), in which TGF-β signaling is blocked. In isolated mouse cardiac fibroblasts, we demonstrated that TGF-β1 treatment decreased steady state PPARγ mRNA (−34%) and protein (−52%) levels, as well as PPARγ transcriptional activity (−53%). Chromatin immunoprecipitation analysis showed that TGF-β1 treatment increased binding of Smad2/3, Smad4 and histone deacetylase 1, and decreased binding of acetylated histone 3 to the PPARγ promoter in cardiac fibroblasts. Both pharmacological activation and overexpression of PPARγ significantly inhibited TGF-β1-induced extracellular matrix molecule expression in isolated cardiac fibroblasts, whereas treatment with the PPARγ agonist rosiglitazone inhibited, and treatment with the PPARγ antagonist T0070907 exacerbated chronic pressure overload-induced cardiac fibrosis and remodeling in wild-type mice in vivo. Conclusion These data provide strong evidence that TGF-β1 directly suppresses PPARγ expression in cardiac fibroblasts via a transcriptional mechanism and suggest that the down-regulation of endogenous PPARγ expression by TGF-β may be involved in pressure overload-induced cardiac fibrosis. PMID:21836474

Pharmacologic inhibition of the enzymatic effects of tissue transglutaminase reduces cardiac fibrosis and attenuates cardiomyocyte hypertrophy following pressure overload.

PubMed

Shinde, Arti V; Su, Ya; Palanski, Brad A; Fujikura, Kana; Garcia, Mario J; Frangogiannis, Nikolaos G

2018-04-01

Tissue transglutaminase (tTG) is a multifunctional protein with a wide range of enzymatic and non-enzymatic functions. We have recently demonstrated that tTG expression is upregulated in the pressure-overloaded myocardium and exerts fibrogenic actions promoting diastolic dysfunction, while preventing chamber dilation. Our current investigation dissects the in vivo and in vitro roles of the enzymatic effects of tTG on fibrotic remodeling in pressure-overloaded myocardium. Using a mouse model of transverse aortic constriction, we demonstrated perivascular and interstitial tTG activation in the remodeling pressure-overloaded heart. tTG inhibition through administration of the selective small molecule tTG inhibitor ERW1041E attenuated left ventricular diastolic dysfunction and reduced cardiomyocyte hypertrophy and interstitial fibrosis in the pressure-overloaded heart, without affecting chamber dimensions and ejection fraction. In vivo, tTG inhibition markedly reduced myocardial collagen mRNA and protein levels and attenuated transcription of fibrosis-associated genes. In contrast, addition of exogenous recombinant tTG to fibroblast-populated collagen pads had no significant effects on collagen transcription, and instead increased synthesis of matrix metalloproteinase (MMP)3 and tissue inhibitor of metalloproteinases (TIMP)1 through transamidase-independent actions. However, enzymatic effects of matrix-bound tTG increased the thickness of pericellular collagen in fibroblast-populated pads. tTG exerts distinct enzymatic and non-enzymatic functions in the remodeling pressure-overloaded heart. The enzymatic effects of tTG are fibrogenic and promote diastolic dysfunction, but do not directly modulate the pro-fibrotic transcriptional program of fibroblasts. Targeting transamidase-dependent actions of tTG may be a promising therapeutic strategy in patients with heart failure and fibrosis-associated diastolic dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

The impact of pressure overload on coronary vascular changes following myocardial infarction in rats.

PubMed

Chen, Jiqiu; Petrov, Artiom; Yaniz-Galende, Elisa; Liang, Lifan; de Haas, Hans J; Narula, Jagat; Hajjar, Roger J

2013-03-01

This study investigates the impact of pressure overload on vascular changes after myocardial infarction (MI) in rats. To evaluate the effect of pressure overload, MI was induced in three groups: 1) left coronary artery ligation for 1 mo (MI-1m), 2) ischemia 30 min/reperfusion for 1 mo (I/R-1m), and 3) ischemia-reperfusion (I/R) was performed after pressure overload induced by aortic banding for 2 mo; 1 mo post-I/R, aortic constriction was released (Ab+I/R+DeAb). Heart function was assessed by echocardiography and in vivo hemodynamics. Resin casting and three-dimensional imaging with microcomputed tomography were used to characterize changes in coronary vasculature. TTC (triphenyltetrazohum chloride) staining and Masson's Trichrome were conducted in parallel experiments. In normal rats, MI induced by I/R and permanent occlusion was transmural or subendocardial. Occluded arterial branches vanished in MI-1m rats. A short residual tail was retained, distal to the occluded site in the ischemic area in I/R-1m hearts. Vascular pathological changes in transmural MI mostly occurred in ischemic areas and remote vasculature remained normal. In pressure overloaded rats, I/R injury induced a sub-MI in which ischemia was transmural, but myocardium in the involved area had survived. The ischemic arterial branches were preserved even though the capillaries were significantly diminished and the pathological changes were extended to remote areas, characterized by fibrosis, atrial thrombus, and pulmonary edema in the Ab+I/R+DeAb group. Pressure overload could increase vascular tolerance to I/R injury, but also trigger severe global ventricular fibrosis and results in atrial thrombus and pulmonary edema.

Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

NASA Technical Reports Server (NTRS)

Tagawa, H.; Wang, N.; Narishige, T.; Ingber, D. E.; Zile, M. R.; Cooper, G. 4th

1997-01-01

We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling

PubMed Central

Yamaguchi, Osamu; Higuchi, Yoshiharu; Hirotani, Shinichi; Kashiwase, Kazunori; Nakayama, Hiroyuki; Hikoso, Shungo; Takeda, Toshihiro; Watanabe, Tetsuya; Asahi, Michio; Taniike, Masayuki; Matsumura, Yasushi; Tsujimoto, Ikuko; Hongo, Kenichi; Kusakari, Yoichiro; Kurihara, Satoshi; Nishida, Kazuhiko; Ichijo, Hidenori; Hori, Masatsugu; Otsu, Kinya

2003-01-01

Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis. PMID:14665690

[Determination of ventricular volumes by a non-geometric method using gamma-cineangiography].

PubMed

Faivre, R; Cardot, J C; Baud, M; Verdenet, J; Berthout, P; Bidet, A C; Bassand, J P; Maurat, J P

1985-08-01

The authors suggest a new way of determining ventricular volume by a non-geometric method using gamma-cineangiography. The results obtained by this method were compared with those obtained by a geometric methods and contrast ventriculography in 94 patients. The new non-geometric method supposes that the radioactive tracer is evenly distributed in the cardiovascular system so that blood radioactivity levels can be measured. The ventricular volume is then equal to the ratio of radioactivity in the LV zone to that of 1 ml of blood. Comparison of the radionuclide and angiographic data in the first 60 patients showed systematic values--despite a satisfactory statistical correlation (r = 0.87, y = 0.30 X + 6.3). This underestimation is due to the phenomenon of attenuation related to the depth of the heart in the thoracic cage and to autoabsorption at source, the degree of which depends on the ventricular volume. An empirical method of calculation allows correction for these factors by taking into account absorption in the tissues by relating to body surface area and autoabsorption at source by correcting for the surface of isotopic ventricular projection expressed in pixels. Using the data of this empirical method, the correction formula for radionuclide ventricular volume is obtained by a multiple linear regression: corrected radionuclide volume = K X measured radionuclide volume (Formula: see text). This formula was applied in the following 34 patients. The correlation between the uncorrected and corrected radionuclide volumes and the angiographic volumes was improved (r = 0.65 vs r = 0.94) and the values were more accurate (y = 0.18 X + 26 vs y = 0.96 X + 1.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance

PubMed Central

Kim, Jiwon; Medicherla, Chaitanya B.; Ma, Claudia L.; Feher, Attila; Kukar, Nina; Geevarghese, Alexi; Goyal, Parag; Horn, Evelyn; Devereux, Richard B.; Weinsaft, Jonathan W.

2016-01-01

Background Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. Methods and Results The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5±3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34±10 vs. 39±9%; p = 0.01) but similar LVEF (40±21 vs. 39±18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17±7 vs. 12±6 kPa; p<0.001) corresponding to increased RV end-systolic volume (143±79 vs. 110±36 ml; p = 0.006), myocardial mass (60±21 vs. 53±17 gm; p = 0.04), and PASP (52±18 vs. 41±18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04–1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14–1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69–1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001). Conclusion Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling. PMID:26799498

Mitral annulus size links ventricular dilatation to functional mitral regurgitation.

PubMed

Popović, Zoran B; Martin, Maureen; Fukamachi, Kiyotaka; Inoue, Masahiro; Kwan, Jun; Doi, Kazuyoshi; Qin, Jian Xin; Shiota, Takahiro; Garcia, Mario J; McCarthy, Patrick M; Thomas, James D

2005-09-01

We compared the impact of annulus size and valve deformation (tethering) on mitral regurgitation in the animal dilated cardiomyopathy model, and assessed if acute left ventricular volume changes affect mitral annulus dimensions. We performed 3-dimensional echocardiography in 30 open-chest dogs with pacing-induced cardiomyopathy. Mitral annulus area was calculated from its two orthogonal diameters, whereas valve tethering was quantified by valve tenting area measurement. Mitral valve regurgitant volume showed the highest correlation with annulus area (r = 0.64, P < .001), left atrial volume (r = 0.40, P < .01), and left ventricular end-diastolic volume (r = 0.37, P < .01). Regurgitant volume showed poorer correlation with valve tethering in both septolateral and intercommissural planes (r = 0.35 and r = 0.31, P < .05 for both). Annulus dimensions correlated with acute changes of left ventricular end-diastolic volume (r = 0.68, P = .002). Mitral annulus dilation is the strongest predictor of functional mitral regurgitation in this animal dilated cardiomyopathy model.

Blood volume-monitored regulation of ultrafiltration in fluid-overloaded hemodialysis patients: study protocol for a randomized controlled trial.

PubMed

Hecking, Manfred; Antlanger, Marlies; Winnicki, Wolfgang; Reiter, Thomas; Werzowa, Johannes; Haidinger, Michael; Weichhart, Thomas; Polaschegg, Hans-Dietrich; Josten, Peter; Exner, Isabella; Lorenz-Turnheim, Katharina; Eigner, Manfred; Paul, Gernot; Klauser-Braun, Renate; Hörl, Walter H; Sunder-Plassmann, Gere; Säemann, Marcus D

2012-06-08

Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, 'final' dry weight is set to normohydration weight -7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters). Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients. ClinicalTrials.gov, NCT01416753.

Blood volume-monitored regulation of ultrafiltration in fluid-overloaded hemodialysis patients: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. Methods/design BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, ‘final’ dry weight is set to normohydration weight −7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters). Discussion Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients. Trial registration ClinicalTrials.gov, NCT01416753 PMID:22682149

Ascorbic acid deficiency, iron overload and alcohol abuse underlie the severe osteoporosis in black African patients with hip fractures--a bone histomorphometric study.

PubMed

Schnitzler, C M; Schnaid, E; MacPhail, A P; Mesquita, J M; Robson, H J

2005-02-01

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.

Caveolin-3 Overexpression Attenuates Cardiac Hypertrophy via Inhibition of T-type Ca2+ Current Modulated by Protein Kinase Cα in Cardiomyocytes*

PubMed Central

Markandeya, Yogananda S.; Phelan, Laura J.; Woon, Marites T.; Keefe, Alexis M.; Reynolds, Courtney R.; August, Benjamin K.; Hacker, Timothy A.; Roth, David M.; Patel, Hemal H.; Balijepalli, Ravi C.

2015-01-01

Pathological cardiac hypertrophy is characterized by subcellular remodeling of the ventricular myocyte with a reduction in the scaffolding protein caveolin-3 (Cav-3), altered Ca2+ cycling, increased protein kinase C expression, and hyperactivation of calcineurin/nuclear factor of activated T cell (NFAT) signaling. However, the precise role of Cav-3 in the regulation of local Ca2+ signaling in pathological cardiac hypertrophy is unclear. We used cardiac-specific Cav-3-overexpressing mice and in vivo and in vitro cardiac hypertrophy models to determine the essential requirement for Cav-3 expression in protection against pharmacologically and pressure overload-induced cardiac hypertrophy. Transverse aortic constriction and angiotensin-II (Ang-II) infusion in wild type (WT) mice resulted in cardiac hypertrophy characterized by significant reduction in fractional shortening, ejection fraction, and a reduced expression of Cav-3. In addition, association of PKCα and angiotensin-II receptor, type 1, with Cav-3 was disrupted in the hypertrophic ventricular myocytes. Whole cell patch clamp analysis demonstrated increased expression of T-type Ca2+ current (ICa, T) in hypertrophic ventricular myocytes. In contrast, the Cav-3-overexpressing mice demonstrated protection from transverse aortic constriction or Ang-II-induced pathological hypertrophy with inhibition of ICa, T and intact Cav-3-associated macromolecular signaling complexes. siRNA-mediated knockdown of Cav-3 in the neonatal cardiomyocytes resulted in enhanced Ang-II stimulation of ICa, T mediated by PKCα, which caused nuclear translocation of NFAT. Overexpression of Cav-3 in neonatal myocytes prevented a PKCα-mediated increase in ICa, T and nuclear translocation of NFAT. In conclusion, we show that stable Cav-3 expression is essential for protecting the signaling mechanisms in pharmacologically and pressure overload-induced cardiac hypertrophy. PMID:26170457

Inhibiting mitochondrial Na+/Ca2+ exchange prevents sudden death in a Guinea pig model of heart failure.

PubMed

Liu, Ting; Takimoto, Eiki; Dimaano, Veronica L; DeMazumder, Deeptankar; Kettlewell, Sarah; Smith, Godfrey; Sidor, Agnieszka; Abraham, Theodore P; O'Rourke, Brian

2014-06-20

In cardiomyocytes from failing hearts, insufficient mitochondrial Ca(2+) accumulation secondary to cytoplasmic Na(+) overload decreases NAD(P)H/NAD(P)(+) redox potential and increases oxidative stress when workload increases. These effects are abolished by enhancing mitochondrial Ca(2+) with acute treatment with CGP-37157 (CGP), an inhibitor of the mitochondrial Na(+)/Ca(2+) exchanger. Our aim was to determine whether chronic CGP treatment mitigates contractile dysfunction and arrhythmias in an animal model of heart failure (HF) and sudden cardiac death (SCD). Here, we describe a novel guinea pig HF/SCD model using aortic constriction combined with daily β-adrenergic receptor stimulation (ACi) and show that chronic CGP treatment (ACi plus CGP) attenuates cardiac hypertrophic remodeling, pulmonary edema, and interstitial fibrosis and prevents cardiac dysfunction and SCD. In the ACi group 4 weeks after pressure overload, fractional shortening and the rate of left ventricular pressure development decreased by 36% and 32%, respectively, compared with sham-operated controls; in contrast, cardiac function was completely preserved in the ACi plus CGP group. CGP treatment also significantly reduced the incidence of premature ventricular beats and prevented fatal episodes of ventricular fibrillation, but did not prevent QT prolongation. Without CGP treatment, mortality was 61% in the ACi group <4 weeks of aortic constriction, whereas the death rate in the ACi plus CGP group was not different from sham-operated animals. The findings demonstrate the critical role played by altered mitochondrial Ca(2+) dynamics in the development of HF and HF-associated SCD; moreover, they reveal a novel strategy for treating SCD and cardiac decompensation in HF. © 2014 American Heart Association, Inc.

Docosahexaenoic acid supplementation alters key properties of cardiac mitochondria and modestly attenuates development of left ventricular dysfunction in pressure overload-induced heart failure.

PubMed

Dabkowski, Erinne R; O'Connell, Kelly A; Xu, Wenhong; Ribeiro, Rogerio F; Hecker, Peter A; Shekar, Kadambari Chandra; Daneault, Caroline; Des Rosiers, Christine; Stanley, William C

2013-12-01

Supplementation with the n3 polyunsaturated fatty acid docosahexaenoic acid (DHA) is beneficial in heart failure patients, however the mechanisms are unclear. DHA is incorporated into membrane phospholipids, which may prevent mitochondrial dysfunction. Thus we assessed the effects of DHA supplementation on cardiac mitochondria and the development of heart failure caused by aortic pressure overload. Pathological cardiac hypertrophy was generated in rats by thoracic aortic constriction. Animals were fed either a standard diet or were supplemented with DHA (2.3 % of energy intake). After 14 weeks, heart failure was evident by left ventricular hypertrophy and chamber enlargement compared to shams. Left ventricle fractional shortening was unaffected by DHA treatment in sham animals (44.1 ± 1.6 % vs. 43.5 ± 2.2 % for standard diet and DHA, respectively), and decreased with heart failure in both treatment groups, but to a lesser extent in DHA treated animals (34.9 ± 1.7 %) than with the standard diet (29.7 ± 1.5 %, P < 0.03). DHA supplementation increased DHA content in mitochondrial phospholipids and decreased membrane viscosity. Myocardial mitochondrial oxidative capacity was decreased by heart failure and unaffected by DHA. DHA treatment enhanced Ca(2+) uptake by subsarcolemmal mitochondria in both sham and heart failure groups. Further, DHA lessened Ca(2+)-induced mitochondria swelling, an index of permeability transition, in heart failure animals. Heart failure increased hydrogen peroxide-induced mitochondrial permeability transition compared to sham, which was partially attenuated in interfibrillar mitochondria by treatment with DHA. DHA decreased mitochondrial membrane viscosity and accelerated Ca(2+) uptake, and attenuated susceptibility to mitochondrial permeability transition and development of left ventricular dysfunction.

Inhibiting Mitochondrial Na+/Ca2+ Exchange Prevents Sudden Death in a Guinea Pig Model of Heart Failure

PubMed Central

Liu, Ting; Takimoto, Eiki; Dimaano, Veronica L.; DeMazumder, Deeptankar; Kettlewell, Sarah; Smith, Godfrey; Sidor, Agnieszka; Abraham, Theodore P.; O’Rourke, Brian

2014-01-01

Rationale In cardiomyocytes from failing hearts, insufficient mitochondrial Ca2+ ([Ca2+]m) accumulation secondary to cytoplasmic Na+ overload decreases NAD(P)H/NAD(P)+ redox potential and increases oxidative stress when workload increases. These effects are abolished by enhancing [Ca2+]m with acute treatment with CGP-37157 (CGP), an inhibitor of the mitochondrial Na+/Ca2+ exchanger. Objective To determine if chronic CGP treatment mitigates contractile dysfunction and arrhythmias in an animal model of heart failure (HF) and sudden cardiac death (SCD). Methods and Results Here, we describe a novel guinea-pig HF/SCD model employing aortic constriction combined with daily β-adrenergic receptor stimulation (ACi) and show that chronic CGP treatment (ACi+CGP) attenuates cardiac hypertrophic remodeling, pulmonary edema, and interstitial fibrosis and prevents cardiac dysfunction and SCD. In the ACi group 4 weeks after pressure-overload, fractional shortening and the rate of left ventricular pressure development decreased by 36% and 32%, respectively, compared to sham-operated controls; in contrast, cardiac function was completely preserved in the ACi+CGP group. CGP treatment also significantly reduced the incidence of premature ventricular beats and prevented fatal episodes of ventricular fibrillation, but did not prevent QT prolongation. Without CGP treatment, mortality was 61% in the ACi group within 4 weeks of aortic constriction, while the death rate in the ACi+CGP group was not different from sham-operated animals. Conclusions The findings demonstrate the critical role played by altered mitochondrial Ca2+ dynamics in the development of HF and HF-associated SCD; moreover, they reveal a novel strategy for treating SCD and cardiac decompensation in HF. PMID:24780171

Mechanism of reduction of mitral regurgitation with vasodilator therapy.

PubMed

Yoran, C; Yellin, E L; Becker, R M; Gabbay, S; Frater, R W; Sonnenblick, E H

1979-04-01

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlin's hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance of left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

A Pilot Study of Quantitative MRI Measurements of Ventricular Volume and Cortical Atrophy for the Differential Diagnosis of Normal Pressure Hydrocephalus

PubMed Central

Moore, Dana W.; Kovanlikaya, Ilhami; Heier, Linda A.; Raj, Ashish; Huang, Chaorui; Chu, King-Wai; Relkin, Norman R.

2012-01-01

Current radiologic diagnosis of normal pressure hydrocephalus (NPH) requires a subjective judgment of whether lateral ventricular enlargement is disproportionate to cerebral atrophy based on visual inspection of brain images. We investigated whether quantitative measurements of lateral ventricular volume and total cortical thickness (a correlate of cerebral atrophy) could be used to more objectively distinguish NPH from normal controls (NC), Alzheimer's (AD), and Parkinson's disease (PD). Volumetric MRIs were obtained prospectively from patients with NPH (n = 5), PD (n = 5), and NC (5). Additional NC (n = 5) and AD patients (n = 10) from the ADNI cohort were examined. Although mean ventricular volume was significantly greater in the NPH group than all others, the range of values overlapped those of the AD group. Individuals with NPH could be better distinguished when ventricular volume and total cortical thickness were considered in combination. This pilot study suggests that volumetric MRI measurements hold promise for improving NPH differential diagnosis. PMID:21860791

Interpretation and use of natriuretic peptides in non-congestive heart failure settings.

PubMed

Tsai, Shih-Hung; Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

2010-03-01

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.

Interpretation and Use of Natriuretic Peptides in Non-Congestive Heart Failure Settings

PubMed Central

Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

2010-01-01

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article. PMID:20191004

Importance of the mitral apparatus for left ventricular function: an experimental approach.

PubMed

Gams, E; Hagl, S; Schad, H; Heimisch, W; Mendler, N; Sebening, F

1992-01-01

In an experimental study of 31 anesthetized dogs the importance of the mitral apparatus for the left ventricular function was investigated. During extracorporeal circulation bileaflet mitral valve prostheses were implanted preserving the mitral subvalvular apparatus. Flexible wires were slung around the chordae tendineae and exteriorized through the left ventricular wall to cut the chordae by electrocautery from the outside when the heart was beating again. External and internal left ventricular dimensions were measured by sonomicrometry, left ventricular stroke volume by electromagnetic flowmeters around the ascending aorta, left ventricular end-diastolic volume by dye dilution technique, and left ventricular pressure by catheter tip manometers. Different preload levels were achieved by volume loading with blood transfusion before and after cutting the chordae tendineae. When the chordae had been divided peak systolic left ventricular pressure did not change. Heart rate only increased at the lowest left ventricular end-diastolic pressures of 3-4 mmHg, but remained unchanged at higher preload levels. Cardiac output decreased significantly up to -9% at left ventricular end-diastolic pressures of 5-10 mmHg, while left ventricular dp/dtmax showed a consistent reduction of up to -15% at any preload level. Significant reductions were also seen in systolic shortening in the left ventricular major axis (by external measurements -27%, by internal recording -43%). Left ventricular end-diastolic dimensions increased in the major axis by +2% when recorded externally, by +10% when measured internally. Systolic and diastolic changes in the minor axis were not consistent and different in the external and internal recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

New classification of geometric ventricular patterns in severe aortic stenosis: Could it be clinically useful?

PubMed

Di Nora, Concetta; Cervesato, Eugenio; Cosei, Iulian; Ravasel, Andreea; Popescu, Bogdan A; Zito, Concetta; Carerj, Scipione; Antonini-Canterin, Francesco; Popescu, Andreea C

2018-04-16

In severe aortic stenosis, different left ventricle (LV) remodeling patterns as a response to pressure overload have distinct hemodynamic profiles, cardiac function, and outcomes. The most common classification considers LV relative wall thickness and LV mass index to create 4 different groups. A new classification including also end-diastolic volume index has been recently proposed. To describe the prevalence of the newly identified remodeling patterns in patients with severe aortic stenosis and to evaluate their clinical relevance according to symptoms. We analyzed 286 consecutive patients with isolated severe aortic stenosis. Current guidelines were used for echocardiographic evaluation. Symptoms were defined as the presence of angina, syncope, or NYHA class III-IV. The mean age was 75 ± 9 years, 156 patients (54%) were men, while 158 (55%) were symptomatic. According to the new classification, the most frequent remodeling pattern was concentric hypertrophy (57.3%), followed by mixed (18.9%) and dilated hypertrophy (8.4%). There were no patients with eccentric remodeling; only 4 patients had a normalLV geometry. Symptomatic patients showed significantly more mixed hypertrophy (P < .05), while the difference regarding the prevalence of the other patterns was not statistically significant. When we analyzed the distribution of the classic 4 patterns stratified by the presence of symptoms, however, we did not find a significant difference (P = .157). The new classification had refined the description of different cardiac geometric phenotypes that develop as a response to pressure overload. It might be superior to the classic 4 patterns in terms of association with symptoms. © 2018 Wiley Periodicals, Inc.

23.4% saline decreases brain tissue volume in severe hepatic encephalopathy as assessed by a quantitative computed tomography marker

PubMed Central

Liotta, Eric M; Lizza, Bryan D; Romanova, Anna L; Guth, James C; Berman, Michael D; Carroll, Timothy J; Francis, Brandon; Ganger, Daniel; Ladner, Daniela P; Maas, Matthew B; Naidech, Andrew M

2016-01-01

Objective Cerebral edema is common in severe hepatic encephalopathy and may be life-threatening. Bolus 23.4% hypertonic saline (HTS) improves surveillance neuromonitoring scores, although its mechanism of action is not clearly established. We investigated the hypothesis that bolus HTS decreases cerebral edema in severe hepatic encephalopathy utilizing a quantitative technique to measure brain and CSF volume changes. Design Retrospective analysis of serial computed tomography (CT) scans and clinical data for a case-control series was performed. Setting Intensive care units of a tertiary care hospital. Patients Patients with severe hepatic encephalopathy treated with 23.4% HTS and control patients who did not receive 23.4% HTS. Methods We used clinically obtained CT scans to measure volumes of the ventricles, intracranial CSF, and brain using a previously validated semi-automated technique (Analyze Direct; Overland Park, KS). Volumes before and after 23.4% HTS were compared with Wilcoxon signed-rank test. Associations between total CSF volume, ventricular volume, serum sodium, and Glasgow Coma Scale Scores were assessed using Spearman correlation. Results Eleven patients with 18 administrations of 23.4% HTS met inclusion criteria. Total CSF (median 47.6 [35.1–69.4] to 61.9 [47.7–87.0] mL, p<0.001) and ventricular volumes (median 8.0 [6.9–9.5] to 9.2 [7.8–11.9] mL, p=0.002) increased and Glasgow Coma Scale Scores improved (median 4 [3–6] to 7 [6–9], p=0.008) after 23.4% HTS. In contrast, total CSF and ventricular volumes decreased in untreated control patients. Serum sodium increase was associated with increase in total CSF volume (r=0.83, p<0.001) and change in total CSF volume was associated with ventricular volume change (r=0.86, p<0.001). Conclusions Total CSF and ventricular volumes increased after 23.4% HTS, consistent with a reduction in brain tissue volume. Total CSF and ventricular volume change may be useful quantitative measures to assess cerebral edema in severe hepatic encephalopathy. PMID:26308431

Left Ventricular Reverse Remodeling With Biventricular Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Heart Failure in the BLOCK HF Trial.

PubMed

St John Sutton, Martin; Plappert, Ted; Adamson, Philip B; Li, Pei; Christman, Shelly A; Chung, Eugene S; Curtis, Anne B

2015-05-01

Biventricular pacing in heart failure (HF) improves survival, relieves symptoms, and attenuates left ventricular (LV) remodeling. However, little is known about biventricular pacing in HF patients with atrioventricular block because they are typically excluded from biventricular trials. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial randomized patients with atrioventricular block, New York Heart Association symptom classes I to III HF, and LV ejection fraction ≤50% to biventricular or right ventricular pacing. Doppler echocardiograms were obtained at randomization (after 30 to 60 days of right ventricular pacing postimplant) and every 6 months through 24 months. Data analysis comparing changes in 10 prespecified echo parameters over time was conducted using a Bayesian design. LV end systolic volume index was also evaluated as a predictor of mortality/morbidity. Of 691 randomized subjects, 624 had paired Doppler echocardiogram data for ≥1 analyses at 6, 12, 18, or 24 months. Biventricular pacing significantly reduced LV volume indices and intraventricular mechanical delay, and improved LV ejection fraction, consistent with LV reverse remodeling. These parameters showed little change with right ventricular pacing alone, indicating no systematic reverse remodeling with right ventricular pacing. LV end systolic volume index was predictive of mortality/morbidity; the estimated risk increased up to 1% for every 1 mL/m(2) increase in LV end systolic volume index. LV end systolic volume index is a significant predictor of mortality/morbidity in this population. Cardiac structure and function are improved with biventricular pacing for patients with atrioventricular block and LV systolic dysfunction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00267098. © 2015 American Heart Association, Inc.

The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

PubMed

Smerup, Morten; Damkjær, Mads; Brøndum, Emil; Baandrup, Ulrik T; Kristiansen, Steen Buus; Nygaard, Hans; Funder, Jonas; Aalkjær, Christian; Sauer, Cathrine; Buchanan, Rasmus; Bertelsen, Mads Frost; Østergaard, Kristine; Grøndahl, Carsten; Candy, Geoffrey; Hasenkam, J Michael; Secher, Niels H; Bie, Peter; Wang, Tobias

2016-02-01

Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It thus remains unexplained how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min(-1), respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, respectively, yielding an ejection fraction of 56±4% and a stroke volume of 0.59 ml kg(-1). Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but produce a lowered cardiac output. © 2016. Published by The Company of Biologists Ltd.

MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload.

PubMed

Ribeiro Junior, Rogério Faustino; Dabkowski, Erinne Rose; Shekar, Kadambari Chandra; O Connell, Kelly A; Hecker, Peter A; Murphy, Michael P

2018-03-01

Heart failure remains a major public-health problem with an increase in the number of patients worsening from this disease. Despite current medical therapy, the condition still has a poor prognosis. Heart failure is complex but mitochondrial dysfunction seems to be an important target to improve cardiac function directly. Our goal was to analyze the effects of MitoQ (100 µM in drinking water) on the development and progression of heart failure induced by pressure overload after 14 weeks. The main findings are that pressure overload-induced heart failure in rats decreased cardiac function in vivo that was not altered by MitoQ. However, we observed a reduction in right ventricular hypertrophy and lung congestion in heart failure animals treated with MitoQ. Heart failure also decreased total mitochondrial protein content, mitochondrial membrane potential in the intermyofibrillar mitochondria. MitoQ restored membrane potential in IFM but did not restore mitochondrial protein content. These alterations are associated with the impairment of basal and stimulated mitochondrial respiration in IFM and SSM induced by heart failure. Moreover, MitoQ restored mitochondrial respiration in heart failure induced by pressure overload. We also detected higher levels of hydrogen peroxide production in heart failure and MitoQ restored the increase in ROS production. MitoQ was also able to improve mitochondrial calcium retention capacity, mainly in the SSM whereas in the IFM we observed a small alteration. In summary, MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload, by decreasing hydrogen peroxide formation, improving mitochondrial respiration and improving mPTP opening. Published by Elsevier Inc.

The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Ghali, Jalal K; Orlandi, Cesare; Abraham, William T

2012-06-01

Volume overload is the dominant feature of decompensated heart failure (HF) and it often results in adverse clinical outcomes. Vasopressin receptor antagonists such as lixivaptan may provide effective volume unloading. This study assessed weight loss after 1 day and 8 weeks of treatment with lixivaptan in outpatients with HF and volume overload. This phase II, 8-week, multicentre, double-blind, parallel-group study randomized participants (2:1) to receive lixivaptan 100 mg or placebo once daily (in addition to standard HF therapy). Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post-treatment. The Trail-making Test, part B (TMT-B) and the Medical Outcomes Survey 6-item cognitive function scale (MOS-6) were assessed at baseline and Week 4. The study randomized 170 participants (lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological therapy for HF at baseline. Demographic characteristics were generally similar between the two groups. Body weight decreased significantly from baseline to Day 1 with lixivaptan vs. placebo (least-square mean change ± standard error: - 0.38 ± 0.08 kg vs. +0.13 ± 0.11 kg; P < 0.001) and at Weeks 1, 2, and 4 (P < 0.01). Cardiovascular changes were generally similar in both groups, though orthopnoea and dyspnoea improved in the lixivaptan group vs. placebo. The TMT-B and MOS-6 showed no significant differences between groups. Lixivaptan was well tolerated-thirst and polyuria occurred more frequently vs. placebo. In outpatients with HF and volume overload, lixivaptan 100 mg once daily, when added to standard therapy, reduced body weight, improved dyspnoea and orthopnoea, and was well tolerated. NCT01055912.

Short-Term Caloric Restriction Suppresses Cardiac Oxidative Stress and Hypertrophy Caused by Chronic Pressure Overload.

PubMed

Kobara, Miyuki; Furumori-Yukiya, Akiko; Kitamura, Miho; Matsumura, Mihoko; Ohigashi, Makoto; Toba, Hiroe; Nakata, Tetsuo

2015-08-01

Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload. Male c57BL6 mice were subjected to ascending aortic constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40% restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC and was continued for 4 weeks. Two weeks after constriction, AAC increased LV wall thickness, impaired transmitral flow velocity, and augmented myocyte hypertrophy and fibrosis, in association with enhancement of BNP and collagen III expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and mitochondrial ROS production were elevated. These changes were significantly attenuated in the CR + AAC group. Additionally, in antioxidant systems, myocardial glutathione peroxidase and superoxide dismutase activities were enhanced in the CR + AAC group. Chronic pressure overload increased cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis. Short-term CR suppressed oxidative stress and improved cardiac function, suggesting that short-term CR could be a useful strategy to prevent pressure overload-induced cardiac injury. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Massie, B.; Kramer, B.L.; Topic, N.

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responsesmore » at rest were decreases in left and right ventricular end-diastolic volumes from 388 +/- 81 to 350 +/- 77 ml and from 52 +/- 26 to 43 +/- 20 volume units, respectively, and in their corresponding filling pressures, from 24 +/- 10 to 17 +/- 9 mm Hg and 10 +/- 5 to 6 +/- 5 mm Hg. Although stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 +/- 6% to 22+/- 5% and from 25 +/- 9% to 29 +/- 11%, respectively. During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. This, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.« less

Ferroportin (Q248H) mutations in African families with dietary iron overload.

PubMed

McNamara, Lynne; Gordeuk, Victor R; MacPhail, A Patrick

2005-12-01

Dietary iron overload found in sub-Saharan Africa might be caused by an interaction between dietary iron and an iron-loading gene. Caucasian people with ferroportin gene mutations have iron overload histologically similar to that found in African patients with iron overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary iron overload, mean cell volume (MCV) and C-reactive protein (CRP) were examined in 19 southern African families. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Statistical analysis was carried out to correlate the presence of the mutation with markers of iron overload and inflammation. We identified three (1.4%) Q248H homozygotes and 53 (24.1%) heterozygotes in the families examined in the present study. There was no increased prevalence of the mutation in index subjects or their families. Logistic regression showed significantly higher serum ferritin concentrations with the mutation. The mean cell volume (MCV) was significantly lower, and the serum CRP significantly higher in subjects who carried the mutation. The present study of 19 families with African iron overload failed to show evidence that the ferroportin (Q248H) mutation is responsible for the condition. Logistic regression, correcting for factors influencing iron status, did show increased ferritin levels in individuals with the mutation. The strong association with low MCV suggests the possibility that the ferroportin (Q248H) mutation might interfere with iron supply, whereas the elevated serum CRP might indicate that the ferroportin mutation influences the inflammatory response in African populations. Copyright 2005 Blackwell Publishing Asia Pty Ltd.

Diffuse diseases of the myocardium: MRI-pathologic review of cardiomyopathies with dilatation.

PubMed

Giesbrandt, Kirk J; Bolan, Candice W; Shapiro, Brian P; Edwards, William D; Mergo, Patricia J

2013-03-01

In this radiologic-pathologic review of the cardiomyopathies, we present the pertinent imaging findings of diffuse myocardial diseases that are associated with ventricular dilatation, including ischemic cardiomyopathy, nonischemic dilated cardiomyopathy, cardiac sarcoidosis, and iron overload cardiomyopathy. Correlation of the key radiologic findings with gross and microscopic pathologic features is presented, to provide the reader with a focused and in-depth review of the pathophysiology underlying each entity and the basis for the corresponding imaging characteristics.

Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

PubMed Central

Huang, Chun-kai; Chen, Bi-yi; Guo, Ang; Chen, Rong; Zhu, Yan-qi; Kutschke, William; Hong, Jiang; Song, Long-sheng

2016-01-01

Aim: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits. Methods: A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg·kg−1·d−1, sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results: TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R2=0.74, P<0.01) and global LV function (R2=0.47, P<0.01). Conclusion: Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure. PMID:26972492

Percutaneous closure of atrial septal defects leads to normalisation of atrial and ventricular volumes

PubMed Central

Teo, Karen SL; Dundon, Benjamin K; Molaee, Payman; Williams, Kerry F; Carbone, Angelo; Brown, Michael A; Worthley, Matthew I; Disney, Patrick J; Sanders, Prashanthan; Worthley, Stephen G

2008-01-01

Background Percutaneous closure of atrial septal defects (ASDs) should potentially reduce right heart volumes by removing left-to-right shunting. Due to ventricular interdependence, this may be associated with impaired left ventricular filling and potentially function. Furthermore, atrial changes post-ASD closure have been poorly understood and may be important for understanding risk of atrial arrhythmia post-ASD closure. Cardiovascular magnetic resonance (CMR) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. We assessed cardiac volumes pre- and post-percutaneous ASD closure using CMR. Methods Consecutive patients (n = 23) underwent CMR pre- and 6 months post-ASD closure. Steady state free precession cine CMR was performed using contiguous slices in both short and long axis views through the ASD. Data was collected for assessment of left and right atrial, ventricular end diastolic volumes (EDV) and end systolic volumes (ESV). Data is presented as mean ± SD, volumes as mL, and paired t-testing performed between groups. Statistical significance was taken as p < 0.05. Results There was a significant reduction in right ventricular volumes at 6 months post-ASD closure (RVEDV: 208.7 ± 76.7 vs. 140.6 ± 60.4 mL, p < 0.0001) and RVEF was significantly increased (RVEF 35.5 ± 15.5 vs. 42.0 ± 15.2%, p = 0.025). There was a significant increase in the left ventricular volumes (LVEDV 84.8 ± 32.3 vs. 106.3 ± 38.1 mL, p = 0.003 and LVESV 37.4 ± 20.9 vs. 46.8 ± 18.5 mL, p = 0.016). However, there was no significant difference in LVEF and LV mass post-ASD closure. There was a significant reduction in right atrial volumes at 6 months post-ASD closure (pre-closure 110.5 ± 55.7 vs. post-closure 90.7 ± 69.3 mL, p = 0.019). Although there was a trend to a decrease in left atrial volumes post-ASD closure, this was not statistically significant (84.5 ± 34.8 mL to 81.8 ± 44.2 mL, p = NS). Conclusion ASD closure leads to normalisation of ventricular volumes and also a reduction in right atrial volume. Further follow-up is required to assess how this predicts outcomes such as risk of atrial arrhythmias after such procedures. PMID:19040763

Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

PubMed

Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

2017-01-23

Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Mitral regurgitation: anatomy is destiny.

PubMed

Athanasuleas, Constantine L; Stanley, Alfred W H; Buckberg, Gerald D

2018-04-26

Mitral regurgitation (MR) occurs when any of the valve and ventricular mitral apparatus components are disturbed. As MR progresses, left ventricular remodelling occurs, ultimately causing heart failure when the enlarging left ventricle (LV) loses its conical shape and becomes globular. Heart failure and lethal ventricular arrhythmias may develop if the left ventricular end-systolic volume index exceeds 55 ml/m2. These adverse changes persist despite satisfactory correction of the annular component of MR. Our goal was to describe this process and summarize evolving interventions that reduce the volume of the left ventricle and rebuild its elliptical shape. This 'valve/ventricle' approach addresses the spherical ventricular culprit and offsets the limits of treating MR by correcting only its annular component.

Fluid overload in hemodialysis patients: a cross-sectional study to determine its association with cardiac biomarkers and nutritional status

PubMed Central

2013-01-01

Background Chronic fluid overload is associated with higher mortality in dialysis patients; however, the link with cardiovascular morbidity has not formally been established and may be influenced by subclinical inflammation. We hypothesized that a relationship exists between fluid overload and [i] cardiovascular laboratory parameter as well as between fluid overload and [ii] inflammatory laboratory parameters. In addition, we aimed to confirm whether volume status correlates with nutritional status. Methods We recorded baseline characteristics of 244 hemodialysis patients at three hemodialysis facilities in Vienna (Austria) and determined associations with volume measurements using the body composition monitor (Fresenius/Germany). In one facility comprising 126 patients, we further analyzed cardiovascular, inflammatory and nutritional parameters. Results We detected predialysis fluid overload (FO) in 39% of all patients (n = 95) with FO defined as ≥15% of extracellular water (ECW). In this subgroup, the absolute FO was 4.4 +/-1.5 L or 22.9 ± 4.8% of ECW. A sub-analysis of patients from one center showed that FO was negatively associated with body mass index (r = -0.371; p = <0.001), while serum albumin was significantly lower in fluid overloaded patients (p = 0.001). FO was positively associated with D-Dimer (r = 0.316; p = 0.001), troponin T (r = 0.325; p < 0.001), and N-terminal pro-B-type natriuretic peptide (r = 0.436; p < 0.001), but not with investigated inflammatory parameters. Conclusions Fluid overload in HD patients was found to be lower in patients with high body mass index, indicating that dry weight was inadequately prescribed and/or difficult to achieve in overweight patients. The association with parameters of cardiovascular compromise and/or damage suggests that fluid overload is a biomarker for cardiovascular risk. Future studies should determine if this applies to patients prior to end-stage renal disease. PMID:24295522

Three-dimensional echocardiographic measurements using automated quantification software for big data processing.

PubMed

Feng, Cheng; Chen, Lixin; Li, Jian; Wang, Jiangtao; Dong, Fajin; Xu, Jinfeng

2017-01-01

To compare a full-automated software to quantify 3D transthoracic echocardiography namely, 3DE-HM (three-dimensional echocardiography HeartModel, Philips Healthcare) with the traditional manual quantitative method (3DE-manual) for assessing volumes of left atrial and ventricular volumes, and left ventricular ejection fraction (LVEF). 3D full volume images acquired from 156 subjects were collected and divided into 3 groups, which include 70 normal control cases (Group A), 17 patients with left ventricular remodeling after acute myocardial infarction (AMI) (Group B), and 69 patients with left atrial remodeling secondary to hypertension (Group C). The 3DE-HM method was used to quantify left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial end-systolic volume (LAESV), and left ventricular ejection fraction (LVEF), respectively. The results were compared with those obtained with the 3DE-manual method for correlation and consistency analyses. The reproducibility of the 3DE-HM method was also evaluated. There was a high correlation between LVEDV, LVESV, LAESV and LVEF values obtained with the 3DE-HM method and those obtained using the 3DE-manual method (r = 0.72 to 0.97). The correlation was strongest for Group B, patients with left ventricular remodeling post-AMI also demonstrated the greatest degree of morphologic changes. There was a significant difference in all parameters measured with the 3DE-HM method in different groups (P < 0.05). The difference in the measurements of LVEDV and LVESV between the two methods was greatest in patients in Group B compared with patients with hypertension-induced left ventricular remodeling (Group C) and in normal controls (Group A) (P < 0.05). Lastly, the difference in the measurement of LAESV between the two methods was greater in patients with hypertension-induced left ventricular remodeling (Group C) than that in the control group (Group A) (P < 0.05). The post-processing time of the 3DE-HM data was significantly shorter than that using the 3DE-manual method (P < 0.05). There was no significant variability in repeated measurements at different time points using the 3DE-HM method either between subjects in different groups or within the same subject. 3DE-HM is a quick and feasible method for left ventricular quantification and is clinically applicable for evaluating patients with left atrial and left ventricular remodeling.

Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor

PubMed Central

Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

2017-01-01

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p<0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, p<0.05) and ejection fraction (82%±3% vs 60%±5%, p<0.05). Treatment with telmisartan provided a comparable level of protection as compared with edaravone in all the parameters measured. Taken together, edaravone treatment ameliorates cardiac fibrosis and improves left ventricular function in the pressure overload rat model, potentially via suppressing the AT1 receptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure. PMID:29081650

Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor.

PubMed

Zhang, Wei-Wei; Bai, Feng; Wang, Jin; Zheng, Rong-Hua; Yang, Li-Wang; James, Erskine A; Zhao, Zhi-Qing

2017-01-01

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p <0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19 mmHg, p <0.05) and ejection fraction (82%±3% vs 60%±5%, p <0.05). Treatment with telmisartan provided a comparable level of protection as compared with edaravone in all the parameters measured. Taken together, edaravone treatment ameliorates cardiac fibrosis and improves left ventricular function in the pressure overload rat model, potentially via suppressing the AT1 receptor-mediated signaling pathways. These data indicate that edaravone might be selected in combination with other existing drugs in preventing progression of cardiac dysfunction in heart failure.

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

Epinephrine and left atrial and left ventricular diastolic function decrease in normal subjects.

PubMed

Fuenmayor, Abdel J; Solórzano, Moisés I; Gómez, Luisangelly

2016-10-01

We assessed the effect of epinephrine over left atrial and left ventricular diastolic function in subjects without structural heart disease. Twenty-seven, 34.6±17.2year-old patients without structural heart disease were included. Intravenous epinephrine (50 to 100ng/kg/min) was infused. Left atrial and ventricular functions were evaluated by means of echocardiography before and during the epinephrine infusion. No complications were observed. Significant increases in heart rate and systolic blood pressure were recorded. Both left atrial (minimal and maximal) volumes increased but increase in the minimal volume was more pronounced, and the ejection fraction diminished. Left atrial expansion index decreased and the fraction of left ventricular inflow volume resulting from atrial contraction increased. Two patients displayed abnormal left ventricular diastolic function. During epinephrine infusion, E/A and e' decreased, and isovolumetric relaxation time increased. In this group of young adults without structural heart disease, epinephrine infusion was safe, did not produce any complications, and induced a small but significant decrease in left atrial function and left ventricular diastolic function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Overexpression of SerpinE2/protease nexin-1 Contribute to Pathological Cardiac Fibrosis via increasing Collagen Deposition

PubMed Central

Li, Xuelian; Zhao, Dandan; Guo, Zhenfeng; Li, Tianshi; Qili, Muge; Xu, Bozhi; Qian, Ming; Liang, Haihai; E, Xiaoqiang; Chege Gitau, Samuel; Wang, Lu; Huangfu, Longtao; Wu, Qiuxia; Xu, Chaoqian; Shan, Hongli

2016-01-01

Although increases in cardiovascular load (pressure overload) are known to elicit ventricular remodeling including cardiomyocyte hypertrophy and interstitial fibrosis, the molecular mechanisms of pressure overload or AngII -induced cardiac interstitial fibrosis remain elusive. In this study, serpinE2/protease nexin-1 was over-expressed in a cardiac fibrosis model induced by pressure-overloaded via transverse aortic constriction (TAC) in mouse. Knockdown of serpinE2 attenuates cardiac fibrosis in a mouse model of TAC. At meantime, the results showed that serpinE2 significantly were increased with collagen accumulations induced by AngII or TGF-β stimulation in vitro. Intriguingly, extracellular collagen in myocardial fibroblast was reduced by knockdown of serpinE2 compared with the control in vitro. In stark contrast, the addition of exogenous PN-1 up-regulated the content of collagen in myocardial fibroblast. The MEK1/2- ERK1/2 signaling probably promoted the expression of serpinE2 via transcription factors Elk1 in myocardial fibroblast. In conclusion, stress-induced the ERK1/2 signaling pathway activation up-regulated serpinE2 expression, consequently led accumulation of collagen protein, and contributed to cardiac fibrosis. PMID:27876880

Direct volume estimation without segmentation

NASA Astrophysics Data System (ADS)

Zhen, X.; Wang, Z.; Islam, A.; Bhaduri, M.; Chan, I.; Li, S.

2015-03-01

Volume estimation plays an important role in clinical diagnosis. For example, cardiac ventricular volumes including left ventricle (LV) and right ventricle (RV) are important clinical indicators of cardiac functions. Accurate and automatic estimation of the ventricular volumes is essential to the assessment of cardiac functions and diagnosis of heart diseases. Conventional methods are dependent on an intermediate segmentation step which is obtained either manually or automatically. However, manual segmentation is extremely time-consuming, subjective and highly non-reproducible; automatic segmentation is still challenging, computationally expensive, and completely unsolved for the RV. Towards accurate and efficient direct volume estimation, our group has been researching on learning based methods without segmentation by leveraging state-of-the-art machine learning techniques. Our direct estimation methods remove the accessional step of segmentation and can naturally deal with various volume estimation tasks. Moreover, they are extremely flexible to be used for volume estimation of either joint bi-ventricles (LV and RV) or individual LV/RV. We comparatively study the performance of direct methods on cardiac ventricular volume estimation by comparing with segmentation based methods. Experimental results show that direct estimation methods provide more accurate estimation of cardiac ventricular volumes than segmentation based methods. This indicates that direct estimation methods not only provide a convenient and mature clinical tool for cardiac volume estimation but also enables diagnosis of cardiac diseases to be conducted in a more efficient and reliable way.

Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops.

PubMed

Dekker, A L A J; Phelps, B; Dijkman, B; van der Nagel, T; van der Veen, F H; Geskes, G G; Maessen, J G

2004-06-01

Patients in heart failure with left bundle branch block benefit from cardiac resynchronization therapy. Usually the left ventricular pacing lead is placed by coronary sinus catheterization; however, this procedure is not always successful, and patients may be referred for surgical epicardial lead placement. The objective of this study was to develop a method to guide epicardial lead placement in cardiac resynchronization therapy. Eleven patients in heart failure who were eligible for cardiac resynchronization therapy were referred for surgery because of failed coronary sinus left ventricular lead implantation. Minithoracotomy or thoracoscopy was performed, and a temporary epicardial electrode was used for biventricular pacing at various sites on the left ventricle. Pressure-volume loops with the conductance catheter were used to select the best site for each individual patient. Relative to the baseline situation, biventricular pacing with an optimal left ventricular lead position significantly increased stroke volume (+39%, P =.01), maximal left ventricular pressure derivative (+20%, P =.02), ejection fraction (+30%, P =.007), and stroke work (+66%, P =.006) and reduced end-systolic volume (-6%, P =.04). In contrast, biventricular pacing at a suboptimal site did not significantly change left ventricular function and even worsened it in some cases. To optimize cardiac resynchronization therapy with epicardial leads, mapping to determine the best pace site is a prerequisite. Pressure-volume loops offer real-time guidance for targeting epicardial lead placement during minimal invasive surgery.

Electrocardiograph-gated single photon emission computed tomography radionuclide angiography presents good interstudy reproducibility for the quantification of global systolic right ventricular function.

PubMed

Daou, Doumit; Coaguila, Carlos; Vilain, Didier

2007-05-01

Electrocardiograph-gated single photon emission computed tomography (SPECT) radionuclide angiography provides accurate measurement of right ventricular ejection fraction and end-diastolic and end-systolic volumes. In this study, we report the interstudy precision and reliability of SPECT radionuclide angiography for the measurement of global systolic right ventricular function using two, three-dimensional volume processing methods (SPECT-QBS, SPECT-35%). These were compared with equilibrium planar radionuclide angiography. Ten patients with chronic coronary artery disease having two SPECT and planar radionuclide angiography acquisitions were included. For the right ventricular ejection fraction, end-diastolic volume and end-systolic volume, the interstudy precision and reliability were better with SPECT-35% than with SPECT-QBS. The sample sizes needed to objectify a change in right ventricular volumes or ejection fraction were lower with SPECT-35% than with SPECT-QBS. The interstudy precision and reliability of SPECT-35% and SPECT-QBS for the right ventricle were better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography on the same population. SPECT-35% and SPECT-QBS present good interstudy precision and reliability for right ventricular function, with the results favouring the use of SPECT-35%. The results are better than those of equilibrium planar radionuclide angiography, but poorer than those previously reported for the left ventricle with SPECT radionuclide angiography. They need to be confirmed in a larger population.

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

Massie, B.; Kramer, B.L.; Topic, N.

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responsesmore » at rest were decreases in left and right ventricular end-diastolic volumes from 388 + 81 to 350 + 77 ml (p < 0.01) and from 52 + 26 to 43 + 20 volume units (p < 0.01), respectively, and in their corresponding filling pressures, from 24 + 10 to 17 + 9 mm Hg and 10 + 5 to and + 5 mm Hg (both p < 0.01). Altough stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 + 6% to 22 + 5% and from 25 + 9% to 29 + 11%, respectively (both p < 0.01). During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. Thus, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.« less

Liver fibrosis marker, 7S domain of collagen type IV, in patients with pre-capillary pulmonary hypertension.

PubMed

Yoshihisa, Akiomi; Kimishima, Yusuke; Kiko, Takatoyo; Sato, Yu; Watanabe, Shunsuke; Kanno, Yuki; Abe, Satoshi; Miyata-Tatsumi, Makiko; Sato, Takamasa; Suzuki, Satoshi; Oikawa, Masayoshi; Kobayashi, Atsushi; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Ishida, Takafumi; Takeishi, Yasuchika

2018-05-01

Pulmonary hypertension (PH) causes right ventricular dysfunction and central venous congestion, and may lead to congestive hepatopathy. The serum 7S domain of collagen type IV (P4NP 7S) is an established marker of liver fibrosis in chronic liver disease. We aimed to determine whether P4NP 7S is related to hemodynamic parameters, and assessed the potential values of P4NP 7S to predict mortality. Consecutive 76 pre-capillary PH patients were divided into tertiles based on their serum P4NP 7S levels. We compared right-heart catheterization, echocardiographic findings, and mortality among the tertiles, and compared P4NP 7S with other known biomarkers of mortality. Cardiac index, mean pulmonary arterial pressure, pulmonary vascular resistance, and right ventricular fractional area change did not differ among the three groups. In contrast, compared to 1st and 2nd tertiles, the 3rd tertile had higher levels of right atrial pressure, right atrial area, and right ventricular area (P<0.05, respectively). In the Kaplan-Meier analysis, mortality progressively increased from the 1st to 2nd and 3rd tertiles (log-rank, P=0.002). In the Cox proportional hazard analysis, P4NP 7S was a predictor of mortality. ROC analysis demonstrated that a P4NP 7S concentration of 4.75ng/ml predicted mortality (AUC 0.85, 95% CI 0.75-0.94; P<0.001), and that the prognostic value of P4NP 7S was comparable or superior to that of other biomarkers (total bilirubin, creatinine, uric acid, C-reactive protein, B-type natriuretic peptide, and troponin I). Serum P4NP 7S is associated with higher central venous pressure, right-sided volume overload, and mortality in PH patients. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Use of Cardiac Computed Tomography for Ventricular Volumetry in Late Postoperative Patients with Tetralogy of Fallot.

PubMed

Kim, Ho Jin; Mun, Da Na; Goo, Hyun Woo; Yun, Tae-Jin

2017-04-01

Cardiac computed tomography (CT) has emerged as an alternative to magnetic resonance imaging (MRI) for ventricular volumetry. However, the clinical use of cardiac CT requires external validation. Both cardiac CT and MRI were performed prior to pulmonary valve implantation (PVI) in 11 patients (median age, 19 years) who had undergone total correction of tetralogy of Fallot during infancy. The simplified contouring method (MRI) and semiautomatic 3-dimensional region-growing method (CT) were used to measure ventricular volumes. All volumetric indices measured by CT and MRI generally correlated well with each other, except for the left ventricular end-systolic volume index (LV-ESVI), which showed the following correlations with the other indices: the right ventricular end-diastolic volume index (RV-EDVI) (r=0.88, p<0.001), the right ventricular end-systolic volume index (RV-ESVI) (r=0.84, p=0.001), the left ventricular end-diastolic volume index (LV-EDVI) (r=0.90, p=0.001), and the LV-ESVI (r=0.55, p=0.079). While the EDVIs measured by CT were significantly larger than those measured by MRI (median RV-EDVI: 197 mL/m 2 vs. 175 mL/m 2 , p=0.008; median LV-EDVI: 94 mL/m 2 vs. 92 mL/m 2 , p=0.026), no significant differences were found for the RV-ESVI or LV-ESVI. The EDVIs measured by cardiac CT were greater than those measured by MRI, whereas the ESVIs measured by CT and MRI were comparable. The volumetric characteristics of these 2 diagnostic modalities should be taken into account when indications for late PVI after tetralogy of Fallot repair are assessed.

Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy.

PubMed

Ellervik, C; Tybjaerg-Hansen, A; Appleyard, M; Ibsen, H; Nordestgaard, B G

2010-09-01

We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH). We analysed data from a cross-sectional study of the general population including 8992 individuals from the Copenhagen City Heart Study (CCHS), a follow-up study of 36,480 individuals from the Copenhagen General Population Study (CGPS), and a case-only study of 3815 Scandinavians from the Losartan Intervention For End-point Reduction in Hypertension Genetic Substudy (LIFEGEN) with LVH and hypertension. In the CCHS, individuals with C282Y/C282Y versus wild type/wild type had an odds ratio for antihypertensive medication use of 4.8 (1.8-13; P = 0.003). In the CGPS, the corresponding hazard ratio was 1.7 (1.0-2.3; P = 0.003). Also, hazard ratios for antihypertensive medication use in the CGPS were 1.6 (1.0-2.6; P = 0.05) for transferrin saturation > or =80% vs. <50%, and 2.3 (1.3-4.2; P = 0.005) for C282Y/C282Y + transferrin saturation > or =80% vs. wild type/wild type + transferrin saturation <50%. These results were most pronounced in men above 55 years of age. We did not find any association between C282Y/C282Y or iron overload and LVH or hypertension (measured as blood pressure at a single occasion or continuous blood pressure), or LVH with hypertension in the CCHS or with severity of LVH in LIFEGEN. We found that haemochromatosis genotype C282Y/C282Y and extremely elevated transferrin saturation either separately or combined were associated with increased risk of antihypertensive medication use. Therefore, testing for haemochromatosis genotype C282Y/C282Y and extreme transferrin saturation could be considered in patients with essential hypertension.

Prostacyclins have no direct inotropic effect on isolated atrial strips from the normal and pressure-overloaded human right heart.

PubMed

Holmboe, Sarah; Andersen, Asger; Jensen, Rebekka V; Kimose, Hans Henrik; Ilkjær, Lars B; Shen, Lei; Clapp, Lucie H; Nielsen-Kudsk, Jens Erik

2017-01-01

Prostacyclins are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostacyclins on right heart function are still not clarified. The aim of this study was to investigate the possible direct inotropic properties of clinical available prostacyclin mimetics in the normal and the pressure-overloaded human right atrium. Trabeculae from the right atrium were collected during surgery from chronic thromboembolic pulmonary hypertension (CTEPH) patients with pressure-overloaded right hearts, undergoing pulmonary thromboendarterectomy (n = 10) and from patients with normal right hearts operated by valve replacement or coronary bypass surgery (n = 9). The trabeculae were placed in an organ bath, continuously paced at 1 Hz. They were subjected to increasing concentrations of iloprost, treprostinil, epoprostenol, or MRE-269, followed by isoprenaline to elicit a reference inotropic response. The force of contraction was measured continuously. The expression of prostanoid receptors was explored through quantitative polymerase chain reaction (qPCR). Iloprost, treprostinil, epoprostenol, or MRE-269 did not alter force of contraction in any of the trabeculae. Isoprenaline showed a direct inotropic response in both trabeculae from the pressure-overloaded right atrium and from the normal right atrium. Control experiments on ventricular trabeculae from the pig failed to show an inotropic response to the prostacyclin mimetics. qPCR demonstrated varying expression of the different prostanoid receptors in the human atrium. In conclusion, prostacyclin mimetics did not increase the force of contraction of human atrial trabeculae from the normal or the pressure-overloaded right heart. These data suggest that prostacyclin mimetics have no direct inotropic effects in the human right atrium.

Tenascin-C promotes chronic pressure overload-induced cardiac dysfunction, hypertrophy and myocardial fibrosis.

PubMed

Podesser, Bruno K; Kreibich, Maximilian; Dzilic, Elda; Santer, David; Förster, Lorenz; Trojanek, Sandra; Abraham, Dietmar; Krššák, Martin; Klein, Klaus U; Tretter, Eva V; Kaun, Christoph; Wojta, Johann; Kapeller, Barbara; Gonçalves, Inês Fonseca; Trescher, Karola; Kiss, Attila

2018-04-01

Left ventricular (LV) hypertrophy is characterized by cardiomyocyte hypertrophy and interstitial fibrosis ultimately leading to increased myocardial stiffness and reduced contractility. There is substantial evidence that the altered expression of matrix metalloproteinases (MMP) and Tenascin-C (TN-C) are associated with the progression of adverse LV remodeling. However, the role of TN-C in the development of LV hypertrophy because of chronic pressure overload as well as the regulatory role of TN-C on MMPs remains unknown. In a knockout mouse model of TN-C, we investigated the effect of 10 weeks of pressure overload using transverse aortic constriction (TAC). Cardiac function was determined by magnetic resonance imaging. The expression of MMP-2 and MMP-9, CD147 as well as myocardial fibrosis were assessed by immunohistochemistry. The expression of TN-C was assessed by RT-qPCR and ELISA. TN-C knockout mice showed marked reduction in fibrosis (P < 0.001) and individual cardiomyocytes size (P < 0.01), in expression of MMP-2 (P < 0.05) and MMP-9 (P < 0.001) as well as preserved cardiac function (P < 0.01) in comparison with wild-type mice after 10 weeks of TAC. In addition, CD147 expression was markedly increased under pressure overload (P < 0.01), irrespectively of genotype. TN-C significantly increased the expression of the markers of hypertrophy such as ANP and BNP as well as MMP-2 in H9c2 cells (P < 0.05, respectively). Our results are pointed toward a novel signaling mechanism that contributes to LV remodeling via MMPs upregulation, cardiomyocyte hypertrophy as well as myocardial fibrosis by TN-C under chronic pressure overload.

Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

PubMed

Schiattarella, Gabriele G; Boccella, Nicola; Paolillo, Roberta; Cattaneo, Fabio; Trimarco, Valentina; Franzone, Anna; D'Apice, Stefania; Giugliano, Giuseppe; Rinaldi, Laura; Borzacchiello, Domenica; Gentile, Alessandra; Lombardi, Assunta; Feliciello, Antonio; Esposito, Giovanni; Perrino, Cinzia

2018-01-01

Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 ( Akap1 -/- ), Akap1 heterozygous ( Akap1 +/- ), and their wild-type ( wt ) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1 -/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 ( Siah2 ) knockout mice ( Siah2 -/- ). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

Myocardial and liver iron overload, assessed using T2* magnetic resonance imaging with an excel spreadsheet for post processing in Tunisian thalassemia major patients.

PubMed

Ouederni, Monia; Ben Khaled, Monia; Mellouli, Fethi; Ben Fraj, Elhem; Dhouib, Nawel; Yakoub, Ismehen Ben; Abbes, Selem; Mnif, Nejla; Bejaoui, Mohamed

2017-01-01

Thalassemia is a common genetic disorder in Tunisia. Early iron concentration assessment is a crucial and challenging issue. Most of annual deaths due to iron overload occurred in underdeveloped regions of the world. Limited access to liver and heart MRI monitoring might partially explain these poor prognostic results. Standard software programs are not available in Tunisia. This study is the first to evaluate iron overload in heart and liver using the MRI T2* with excel spreadsheet for post processing. Association of this MRI tool results to serum ferritin level, and echocardiography was also investigated. One hundred Tunisian-transfused thalassemia patients older than 10 years (16.1 ± 5.2) were enrolled in the study. The mean myocardial iron concentration (MIC) was 1.26 ± 1.65 mg/g dw (0.06-8.32). Cardiac T2* (CT2*) was under 20 ms in 30 % of patients and under 10 ms in 21 % of patients. Left ventricular ejection function was significantly lower in patients with CT2* <10 ms. Abnormal liver iron concentration (LIC >3 mg/g dw) was found in 95 % of patients. LIC was over 15 mg/g dw in 25 % of patients. MIC was more correlated than CT2* to LIC and serum ferritin. Among patients with SF <1000 μg/l, 13 % had CT2* <20 ms. Our data showed that 30 % of the Tunisian thalassemia major patients enrolled in this cohort had myocardial iron overload despite being treated by iron chelators. SF could not reliably predict iron overload in all thalassemia patients. MRI T2* using excel spreadsheet for routine follow-up of iron overload might improve the prognosis of thalassemia major patients in developing countries, such as Tunisia, where standard MRI tools are not available or expensive.

Iloprost improves ventricular function in the hypertrophic and functionally impaired right heart by direct stimulation.

PubMed

Holmboe, Sarah; Andersen, Asger; Vildbrad, Mads D; Nielsen, Jan M; Ringgaard, Steffen; Nielsen-Kudsk, Jens E

2013-12-01

Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure-overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; [Formula: see text]), pulmonary trunk banding (PTB; [Formula: see text]), or a sham operation ([Formula: see text]). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a [Formula: see text] ([Formula: see text]) increase in stroke volume in the sham group and a [Formula: see text] ([Formula: see text]) increase in the PTB group. RV [Formula: see text] was elevated by [Formula: see text] ([Formula: see text]) in the sham group and by [Formula: see text] ([Formula: see text]) in the PTB group. An elevation in cardiac output of [Formula: see text] ([Formula: see text]) and an [Formula: see text] ([Formula: see text]) increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.

Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling.

PubMed

Moro, Cécile; Jouan, Marie-Gabrielle; Rakotovao, Andry; Toufektsian, Marie-Claire; Ormezzano, Olivier; Nagy, Norbert; Tosaki, Arpad; de Leiris, Joël; Boucher, François

2007-11-01

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.

Common presentation of rare diseases: Left ventricular hypertrophy and diastolic dysfunction.

PubMed

Linhart, Ales; Cecchi, Franco

2018-04-15

Left ventricular hypertrophy may be a consequence of a hemodynamic overload or a manifestation of several diseases affecting different structural and functional proteins of cardiomyocytes. Among these, sarcomeric hypertrophic cardiomyopathy (HCM) represents the most frequent cause. In addition, several metabolic diseases lead to myocardial thickening, either due to intracellular storage (glycogen storage and lysosomal diseases), extracellular deposition (TTR and AL amyloidosis) or due to abnormal energy metabolism (mitochondrial diseases). The recognition of these rare causes of myocardial hypertrophy is important for family screening strategies, risk assessment, and treatment. Moreover, as there are specific therapies for some forms of HCM including enzyme substitution and chaperone therapies and specific treatments for TTR amyloidosis, a differential diagnosis should be sought in all patients with unexplained left ventricular hypertrophy. Diastolic dysfunction is a key feature of HCM and its phenocopies. Its assessment is complex and requires evaluation of several functional parameters and structural changes. Severe diastolic dysfunction carries a negative prognostic implication and its value in differential diagnosis is limited. Copyright © 2018 Elsevier B.V. All rights reserved.

Extracellular Superoxide Dismutase Deficiency Exacerbates Pressure Overload–Induced Left Ventricular Hypertrophy and Dysfunction

PubMed Central

Lu, Zhongbing; Xu, Xin; Hu, Xinli; Zhu, Guangshuo; Zhang, Ping; van Deel, Elza D.; French, Joel P.; Fassett, John T.; Oury, Tim D.; Bache, Robert J.; Chen, Yingjie

2008-01-01

Extracellular superoxide dismutase (SOD) contributes only a small fraction to total SOD activity in the normal heart but is strategically located to scavenge free radicals in the extracellular compartment. To examine the physiological significance of extracellular SOD in the response of the heart to hemodynamic stress, we studied the effect of extracellular SOD deficiency on transverse aortic constriction (TAC)–induced left ventricular remodeling. Under unstressed conditions extracellular SOD deficiency had no effect on myocardial total SOD activity, the ratio of glutathione:glutathione disulfide, nitrotyrosine content, or superoxide anion production but resulted in small but significant increases in myocardial fibrosis and ventricular mass. In response to TAC for 6 weeks, extracellular SOD-deficient mice developed more severe left ventricular hypertrophy (heart weight increased 2.56-fold in extracellular SOD-deficient mice as compared with 1.99-fold in wild-type mice) and pulmonary congestion (lung weight increased 2.92-fold in extracellular SOD-deficient mice as compared with 1.84-fold in wild-type mice). Extracellular SOD-deficient mice also had more ventricular fibrosis, dilation, and a greater reduction of left ventricular fractional shortening and rate of pressure development after TAC. TAC resulted in greater increases of ventricular collagen I, collagen III, matrix metalloproteinase-2, matrix metalloproteinase-9, nitrotyrosine, and superoxide anion production. TAC also resulted in a greater decrease of the ratio of glutathione:glutathione disulfide in extracellular SOD-deficient mice. The finding that extracellular SOD deficiency had minimal impact on myocardial overall SOD activity but exacerbated TAC induced myocardial oxidative stress, hypertrophy, fibrosis, and dysfunction indicates that the distribution of extracellular SOD in the extracellular space is critically important in protecting the heart against pressure overload. PMID:17998475

Association between hippuric acid and left ventricular hypertrophy in maintenance hemodialysis patients.

PubMed

Yu, Teng-Hung; Tang, Wei-Hua; Lu, Yung-Chuan; Wang, Chao-Ping; Hung, Wei-Chin; Wu, Cheng-Ching; Tsai, I-Ting; Chung, Fu-Mei; Houng, Jer-Yiing; Lan, Wen-Chun; Lee, Yau-Jiunn

2018-05-22

Left ventricular hypertrophy (LVH) is one of the most common cardiac abnormalities in patients with end-stage renal disease. Hippuric acid (HA), a harmful uremic toxin, is known to be elevated in patients with uremia, and serum HA levels are associated with neurological symptoms, metabolic acidosis, and accelerated renal damage associated with chronic kidney disease. However, the pathophysiological role of HA in patients with uremia remains unclear. We investigated the association between serum HA levels and echocardiographic measurements in patients undergoing hemodialysis (HD) treatment. Eighty consecutive patients treated at a single HD center (44 males, 36 females; mean age 66 y, mean HD duration 6 y) were included in this study. Comprehensive echocardiography was performed after HD. Blood samples were obtained before HD. Pearson's correlation analysis revealed that serum HA levels were positively correlated with diastolic blood pressure, serum creatinine, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-diastolic diameter, left ventricular end systolic diameter, end systolic left ventricular posterior wall thickness, and left atrium diameter, and negatively correlated with age. Furthermore, the HD patients with LVH had higher median serum HA levels than those without LVH (34.2 vs. 18.1 μg/ml, p = 0.003). Multiple logistic regression analysis revealed that HA was independently associated with LVH even after adjusting for known biomarkers. Moreover, the receiver operator characteristics curve of HA showed that a HA level of >26.9 μg/ml was associated with LVH. HA was significantly associated with LVH. HA could be a novel biomarker of left ventricular overload, which is closely associated with an increased risk of death in HD patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Early results of MitraClip system implantation by real-time three-dimensional speckle-tracking left ventricle analysis.

PubMed

Scandura, Salvatore; Dipasqua, Fabio; Gargiulo, Giuseppe; Capodanno, Davide; Caggegi, Anna; Grasso, Carmelo; Mangiafico, Sarah; Pistritto, Anna Maria; Immè, Sebastiano; Chiarandà, Marta; Ministeri, Margherita; Ronsivalle, Giuseppe; Cannata, Stefano; Arcidiacono, Antonio Andrea; Capranzano, Piera; Tamburino, Corrado

2016-11-01

To appraise the early effect of percutaneous mitral valve repair with the MitraClip system on myocardial function using real-time three-dimensional speckle-tracking echocardiography (3D-STE). Consecutive patients with moderate-to-severe or severe mitral regurgitation, undergoing mitral valve repair with the MitraClip system, were prospectively evaluated during the peri-procedural workout and follow-up. Left ventricular deformation was evaluated by a two-dimensional and 3D speckle-tracking analysis. 3D-STE acquisitions were elaborated obtaining real-time 3D global longitudinal strain evaluation, and by appraising both volumetric and hemodynamic parameters (i.e. left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, cardiac output, and stroke volume). In all, 30 patients were included. At 1-month follow-up, 3D-STE analysis revealed no changes in left ventricular end-diastolic volume (162.6 ± 73.7 ml at baseline vs. 159.8 ± 64.5 ml at 1-month follow-up; P = 0.63) and a downward trend in left ventricular end-systolic volume (104.7 ± 52.0 vs. 100.1 ± 50.4 ml, respectively; P = 0.06). Left ventricular ejection fraction did not significantly increase (38.1 ± 11.3% at baseline vs. 39.4 ± 11.0% at 1-month follow-up; P = 0.20). No significant changes were reported in cardiac output (4.3 ± 2.0 l/min at baseline vs. 4.0 ± 1.5 l/min at follow-up; P = 0.377) and in stroke volume (59.5 ± 25.5 ml at baseline vs. 59.9 ± 20.7 ml at follow-up; P = 0.867). On the contrary, left ventricular deformation capability significantly improved, with the real-time 3D global longitudinal strain value changing from -9.8 ± 4.1% at baseline to -11.0 ± 4.4% at follow-up (P = 0.018). Accurately assessing myocardial function by the use of 3D-STE, this study reported irrelevant early changes in left ventricular size, but a positive effect on left ventricular deformation capability following mitral valve repair with the MitraClip system. These preliminary results need to be confirmed in larger series and extended to long-term follow-up.

Mechanisms of reoxygenation-induced calcium overload in cultured chick embryo heart cells

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

Murphy, J.G.; Smith, T.W.; Marsh, J.D.

1988-06-01

We examined mechanisms by which Ca enters cultured myocardial cells during posthypoxic reoxygenation. Monolayer cultures of chick embryo ventricular cells were prepared from hearts 10 days in ovo. Cells were exposed to hypoxic conditions (PO/sub 2/ less than 1.5 Torr), and /sup 45/Ca uptake during subsequent reoxygenation was then examined in the absence and presence of modulators of Ca channel-dependent Ca entry and Na-Ca exchange. Modulation of Ca entry by free radical-scavenging enzymes was also examined. Hypoxia for 120 min followed by reoxygenation increased Ca content from 1.9 to 6.1 nmol/mg protein (P less than 0.05) at 30 min. Verapamilmore » (10(-5) M) added before reoxygenation reduced Ca overload to 3.1 +/- 0.2 nmol/mg protein (P less than 0.05), but both verapamil and BAY K 8644 were without effect on modulating Ca entry if added 30 min after reoxygenation. /sup 24/Na content of cells increased from 70 nmol/mg protein in control cells to 157 nmol/mg protein (P less than 0.05) after hypoxia and reoxygenation, favoring Ca entry via Na-Ca exchange. Dichlorobenzamil significantly ameliorated reoxygenation-induced Ca overload, as did catalase and superoxide dismutase. We conclude that reoxygenation-induced Ca overload is unlikely to occur via the Ca channel. It occurs in part via Na-Ca exchange and is substantially ameliorated by enzymatic O/sub 2/ free radical scavengers.« less

Renal function in juvenile rats subjected to prenatal malnutrition and chronic salt overload.

PubMed

Magalhães, João Carlos G; da Silveira, Alex B; Mota, Diogenes L; Paixão, Ana Durce O

2006-05-01

Dietary sodium may contribute to hypertension and to cardiovascular and renal disease if a primary deficiency of the kidney to excrete sodium exists. In order to investigate whether chronic 1% NaCl in the drinking water changes blood pressure and renal haemodynamics in juvenile Wistar rats subjected to prenatal malnutrition, an evaluation of plasma volume, oxidative stress in the kidney, proteinuria and renal haemodynamics was carried out. Malnutrition was induced by a multideficient diet. Mean arterial pressure, renal blood flow and glomerular filtration rate (GFR) were measured using a blood pressure transducer, a flow probe and inulin clearance, respectively. Plasma volume and oxidative stress were measured by means of the Evans Blue method and by monitoring thiobarbituric acid reactive substances (TBARS) in the kidneys, respectively. Urinary protein was measured by precipitation with 3% sulphosalicylic acid. It was observed that prenatally malnourished rats presented higher values of plasma volume (26%, P < 0.05), kidney TBARS (43%, P < 0.01) and blood pressure (10%, P < 0.01) when compared with the control group. However, they showed no change in renal haemodynamics or proteinuria. Neither prenatally malnourished nor control rats treated with sodium overload presented plasma volume or blood pressure values different from their respective control groups, but both groups presented elevated proteinuria (P < 0.01). The prenatally malnourished group treated with sodium overload presented higher values of kidney TBARS, GFR and filtration fraction (58, 87 and 72% higher, respectively, P < 0.01) than its respective control group. In summary, sodium overload did not exacerbate the hypertension in juvenile prenatally malnourished rats, but induced renal haemodynamic adjustments compatible with the development of renal disease.

Effect of Progressive Volume-Based Overload During Plyometric Training on Explosive and Endurance Performance in Young Soccer Players.

PubMed

Ramírez-Campillo, Rodrigo; Henríquez-Olguín, Carlos; Burgos, Carlos; Andrade, David C; Zapata, Daniel; Martínez, Cristian; Álvarez, Cristian; Baez, Eduardo I; Castro-Sepúlveda, Mauricio; Peñailillo, Luis; Izquierdo, Mikel

2015-07-01

The purpose of the study was to compare the effects of progressive volume-based overload with constant volume-based overload on muscle explosive and endurance performance adaptations during a biweekly short-term (i.e., 6 weeks) plyometric training intervention in young soccer players. Three groups of young soccer players (age 13.0 ± 2.3 years) were divided into: control (CG; n = 8) and plyometric training with (PPT; n = 8) and without (NPPT; n = 8) a progressive increase in volume (i.e., 16 jumps per leg per week, with an initial volume of 80 jumps per leg each session). Bilateral and unilateral horizontal and vertical countermovement jump with arms (CMJA), 20-cm drop jump reactive strength index (RSI20), maximal kicking velocity (MKV), 10-m sprint, change of direction speed (CODS), and Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1) were measured. Although both experimental groups significantly increased CMJA, RSI20, CODS, and endurance performance, only PPT showed a significant improvement in MKV and 10-m sprint time. In addition, only PPT showed a significantly higher performance improvement in jumping, MKV, and Yo-Yo IR1 compared with CG. Also, PPT showed higher meaningful improvement compared with NPPT in all (except 1) jump performance measures. Furthermore, although PPT involved a higher total volume compared with NPPT, training efficiency (i.e., percentage change in performance/total jump volume) was similar between groups. Our results show that PPT and NPPT ensured significant improvement in muscle explosive and endurance performance measures. However, a progressive increase in plyometric training volume seems more advantageous to induce soccer-specific performance improvements.

Myocardial scar location as detected by cardiac magnetic resonance is associated with the outcome in heart failure patients undergoing surgical ventricular reconstruction.

PubMed

Castelvecchio, Serenella; Careri, Giulia; Ambrogi, Federico; Camporeale, Antonia; Menicanti, Lorenzo; Secchi, Francesco; Lombardi, Massimo

2018-01-01

Post-infarction myocardial scar causes adverse left ventricular remodelling and negatively affects the prognosis. We sought to investigate whether scar extent and location obtained by cardiac magnetic resonance may affect the reverse remodelling and survival of heart failure patients undergoing surgical ventricular reconstruction. From January 2011 to December 2015, 151 consecutive patients with previous myocardial infarction and left ventricular remodelling underwent surgical ventricular reconstruction at our Institution, of which 88 (58%) patients had a preoperative protocol-standardized late gadolinium enhancement (LGE)-cardiac magnetic resonance examination during the week before surgery. We excluded 40 patients with devices (26%), 15 patients with irregular heart rhythm (permanent atrial fibrillation, 10% not included in the device group) or mixed contraindications (severe claustrophobia or presence of material magnetic resonance not compatible). Among the 145 survivors, 11 patients received an implantable cardioverter defibrillator after surgery (mostly for persistent low ejection fraction) and were excluded as well, yielding a total of 59 patients (48 men, aged 65 ± 9 years) who repeated a protocol-standardized LGE-cardiac magnetic resonance examination even 6 months postoperatively and therefore represent the study population. Patients were grouped according to the presence of LGE in the antero-basal left ventricular segments (Group A) or the absence of LGE in the same segments (Group B). The postoperative left ventricular end-systolic volume index was considered the primary end-point. After surgery, left ventricular end-systolic volume index and end-diastolic volume index significantly decreased (P < 0.001, for both), while diastolic sphericity index and ejection fraction significantly increased (P = 0.015 and P < 0.001, respectively). The presence of LGE in the antero-basal left ventricular segments (10 patients, Group A) was the only independent predictor of outcome (P = 0.02) at multivariate analysis, being the postoperative left ventricular end-systolic volume index significantly higher compared to that of patients of Group B (49 patients) (78 ± 26 ml/m2 vs 55 ± 20 ml/m2, P = 0.003). Furthermore, patients with a postoperative left ventricular end-systolic volume index >60 ml/m2 showed a higher risk of cardiac events (hazard ratio = 3.67, P = 0.02). In patients undergoing surgical ventricular reconstruction, LGE scar location affects the left ventricular reverse remodelling, which in turn might limit the survival benefit. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Thyroid-stimulating hormone and adverse left ventricular remodeling following ST-segment elevation myocardial infarction.

PubMed

Reindl, Martin; Feistritzer, Hans-Josef; Reinstadler, Sebastian Johannes; Mueller, Lukas; Tiller, Christina; Brenner, Christoph; Mayr, Agnes; Henninger, Benjamin; Mair, Johannes; Klug, Gert; Metzler, Bernhard

2018-04-01

Adverse left ventricular remodeling is one of the major determinants of heart failure and mortality in patients surviving ST-segment elevation myocardial infarction (STEMI). The hypothalamic-pituitary-thyroid axis is a key cardiovascular regulator; however, the relationship between hypothalamic-pituitary-thyroid status and post-STEMI left ventricular remodeling is unclear. We aimed to investigate the association between thyroid-stimulating hormone concentrations and the development of left ventricular remodeling following reperfused STEMI. In this prospective observational study of 102 consecutive STEMI patients, thyroid-stimulating hormone levels were measured at the first day after infarction and 4 months thereafter. Cardiac magnetic resonance scans were performed within the first week as well as at 4 months follow-up to determine infarct characteristics, myocardial function and as primary endpoint left ventricular remodeling, defined as a 20% or greater increase in left ventricular end-diastolic volume. Patients with left ventricular remodeling ( n=15, 15%) showed significantly lower concentrations of baseline (1.20 [0.92-1.91] vs. 1.73 [1.30-2.60] mU/l; P=0.02) and follow-up (1.11 [0.86-1.28] vs. 1.51 [1.15-2.02] mU/l; P=0.002) thyroid-stimulating hormone. The association between baseline thyroid-stimulating hormone and left ventricular remodeling remained significant after adjustment for major clinical (peak high-sensitivity cardiac troponin T and C-reactive protein, heart rate; odds ratio (OR) 5.33, 95% confidence interval (CI) 1.52-18.63; P=0.01) and cardiac magnetic resonance predictors of left ventricular remodeling (infarct size, microvascular obstruction, ejection fraction; OR 4.59, 95% CI 1.36-15.55; P=0.01). Furthermore, chronic thyroid-stimulating hormone was related to left ventricular remodeling independently of chronic left ventricular remodeling correlates (infarct size, ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume; OR 9.22, 95% CI 1.69-50.22; P=0.01). Baseline and chronic thyroid-stimulating hormone concentrations following STEMI were independently associated with left ventricular remodeling, proposing a novel pathophysiological axis in the development of post-STEMI left ventricular remodeling.

Cardiovascular magnetic resonance of cardiac function and myocardial mass in preterm infants: a preliminary study of the impact of patent ductus arteriosus

PubMed Central

2014-01-01

Background Many pathologies seen in the preterm population are associated with abnormal blood supply, yet robust evaluation of preterm cardiac function is scarce and consequently normative ranges in this population are limited. The aim of this study was to quantify and validate left ventricular dimension and function in preterm infants using cardiovascular magnetic resonance (CMR). An initial investigation of the impact of the common congenital defect patent ductus arteriosus (PDA) was then carried out. Methods Steady State Free Procession short axis stacks were acquired. Normative ranges of left ventricular end diastolic volume (EDV), stroke volume (SV), left ventricular output (LVO), ejection fraction (EF), left ventricular (LV) mass, wall thickness and fractional thickening were determined in “healthy” (control) neonates. Left ventricular parameters were then investigated in PDA infants. Unpaired student t-tests compared the 2 groups. Multiple linear regression analysis assessed impact of shunt volume in PDA infants, p-value ≤ 0.05 being significant. Results 29 control infants median (range) corrected gestational age at scan 34+6(31+1-39+3) weeks were scanned. EDV, SV, LVO, LV mass normalized by weight and EF were shown to decrease with increasing corrected gestational age (cGA) in controls. In 16 PDA infants (cGA 30+3(27+3-36+1) weeks) left ventricular dimension and output were significantly increased, yet there was no significant difference in ejection fraction and fractional thickening between the two groups. A significant association between shunt volume and increased left ventricular mass correcting for postnatal age and corrected gestational age existed. Conclusion CMR assessment of left ventricular function has been validated in neonates, providing more robust normative ranges of left ventricular dimension and function in this population. Initial investigation of PDA infants would suggest that function is relatively maintained. PMID:25160730

Interstudy reproducibility of dimensional and functional measurements between cine magnetic resonance studies in the morphologically abnormal left ventricle.

PubMed

Semelka, R C; Tomei, E; Wagner, S; Mayo, J; Caputo, G; O'Sullivan, M; Parmley, W W; Chatterjee, K; Wolfe, C; Higgins, C B

1990-06-01

The validity of geometric formulas to derive mass and volumes in the morphologically abnormal left ventricle is problematic. Imaging techniques that are tomographic and therefore inherently three-dimensional should be more reliable and reproducible between studies in such ventricles. Determination of reproducibility between studies is essential to define the limits of an imaging technique for evaluating the response to therapy. Sequential cine magnetic resonance (MR) studies were performed on patients with dilated cardiomyopathy (n = 11) and left ventricular hypertrophy (n = 8) within a short interval in order to assess interstudy reproducibility. Left ventricular mass, volumes, ejection fraction, and end-systolic wall stress were determined by two independent observers. Between studies, left ventricular mass was highly reproducible for hypertrophied and dilated ventricles, with percent variability less than 6%. Ejection fraction and end-diastolic volume showed close reproducibility between studies, with percent variability less than 5% End-systolic volume varied by 4.3% and 4.5% in dilated cardiomyopathy and 8.4% and 7.2% in left ventricular hypertrophy for the two observers. End-systolic wall stress, which is derived from multiple measurements, varied the greatest, with percent variability of 17.2% and 15.7% in dilated cardiomyopathy and 14.8% and 13% in left ventricular hypertrophy, respectively. The results of this study demonstrate that mass, volume, and functional measurements are reproducible in morphologically abnormal ventricles.

Relationship between right and left ventricular function in candidates for implantable cardioverter defibrillator with low left ventricular ejection fraction.

PubMed

Jimenez-Juan, Laura; Karur, Gauri R; Connelly, Kim A; Deva, Djeven; Yan, Raymond T; Wald, Rachel M; Singh, Sheldon; Leung, General; Oikonomou, Anastasia; Dorian, Paul; Angaran, Paul; Yan, Andrew T

2017-04-01

Indications for the primary prevention of sudden death using an implantable cardioverter defibrillator (ICD) are based predominantly on left ventricular ejection fraction (LVEF). However, right ventricular ejection fraction (RVEF) is also a known prognostic factor in a variety of structural heart diseases that predispose to sudden cardiac death. We sought to investigate the relationship between right and left ventricular parameters (function and volume) measured by cardiovascular magnetic resonance (CMR) among a broad spectrum of patients considered for an ICD. In this retrospective, single tertiary-care center study, consecutive patients considered for ICD implantation who were referred for LVEF assessment by CMR were included. Right and left ventricular function and volumes were measured. In total, 102 patients (age 62±14 years; 23% women) had a mean LVEF of 28±11% and RVEF of 44±12%. The left ventricular and right ventricular end diastolic volume index was 140±42 mL/m 2 and 81±27 mL/m 2 , respectively. Eighty-six (84%) patients had a LVEF <35%, and 63 (62%) patients had right ventricular systolic dysfunction. Although there was a significant and moderate correlation between LVEF and RVEF ( r =0.40, p <0.001), 32 of 86 patients (37%) with LVEF <35% had preserved RVEF, while 9 of 16 patients (56%) with LVEF ≥35% had right ventricular systolic dysfunction (Kappa=0.041). Among patients being considered for an ICD, there is a positive but moderate correlation between LVEF and RVEF. A considerable proportion of patients who qualify for an ICD based on low LVEF have preserved RVEF, and vice versa.

Change of heart dimensions and function during pregnancy in goats.

PubMed

Szaluś-Jordanow, Olga; Czopowicz, Michał; Witkowski, Lucjan; Moroz, Agata; Mickiewicz, Marcin; Frymus, Tadeusz; Markowska-Daniel, Iwona; Bagnicka, Emilia; Kaba, Jarosław

2018-03-08

The study aimed to evaluate the effect of pregnancy on heart diameters and function in goats. Transthoracic echocardiography of 12 female dairy goats of two Polish regional breeds was performed. A Mindray M7 diagnostic ultrasound system with Phased Array transducer was used. Simultaneously, electrocardiography was recorded. All animals were examined four times - at mating season, at the end of the first trimester, at the end of the second trimester and just before kidding. Eleven measurements were taken each time: aortic and left atrial diameter (AoD and LAD), right and left ventricular internal diameter in diastole (RVIDd and LVIDd), left ventricular internal diameter in systole (LVIDs), inter-ventricular septum thickness in diastole and systole (IVSd and IVSd) and left ventricular posterior wall in diastole and systole (LVPWd and LVPWs), maximum left and right ventricular outflow tract velocity (RVOT Vmax and LVOT Vmax). Nine consecutive measurements were derived: the ratio of the left atrial diameter to the aortic diameter (AoD/LAD), left ventricular fractional shortening (FS%), left ventricular ejection fraction (EF%), maximum outflow tract pressure gradients (RVOT PGmax and LVOT PGmax), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV), stroke volume (SV) and cardiac output (CO). HR, LAD, LVPWs, IVSs increased significantly in the first trimester. AoD and RVIDd were significantly higher around parturition. LVIDd, FS%, EF%, SV and CO rose both in the first and third trimester. No measurement decreased during pregnancy. The study confirms that pregnancy causes changes in the heart size and functioning. Copyright © 2018. Published by Elsevier Ltd.

Volumetric measurements in patients with corrected tetralogy of Fallot: comparison of short-axis versus axial cardiac MRI and echocardiography.

PubMed

Schelhorn, Juliane; Neudorf, Ulrich; Schemuth, Haemi; Nensa, Felix; Nassenstein, Kai; Schlosser, Thomas W

2015-11-01

Patients with corrected tetralogy of Fallot (cToF) are prone to develop pulmonary regurgitation and right ventricular enlargement resulting in long-term complications, thus correct right ventricular volumetric monitoring is crucial. However, it remains controversial which cardiovascular magnetic resonance imaging (CMRI) slice orientation is most appropriate in cToF for the analysis of the right ventricular volume. To investigate which slice orientation is most suited for right ventricular volumetry in cToF we compared short-axis and axial slices, and furthermore we compared right ventricular data between CMRI and echocardiography. Thirty CMRI examinations of 27 patients with cToF were included retrospectively. Right ventricular end-diastolic (EDV) and end-systolic volume (ESV) were derived from short-axis and axial cine CMRI planes. Furthermore, pulmonary trunk forward flow in phase-contrast CMRI and right ventricular inner diastolic diameter in echocardiography (R VIDdiast) were measured. By Bland-Altman and variance analysis intra- and inter-observer agreement were assessed for cine CMRI data. By Pearson correlation CMRI cine and phase-contrast data and CMRI cine and echocardiographic data were compared. Intra- and inter-observer variability for right ventricular EDV were significantly lower in axial slices (P = 0.016, P = 0.010). For right ventricular ESV a trend towards a lower intra- and inter-observer variability in axial slices was found (P = 0.063, P = 0.138). Right ventricular stroke volume in short-axis (r = 0.872, P < 0.001) and in axial (r = 0.914, P < 0.001) planes correlated highly, respectively very highly with pulmonary trunk forward flow in phase-contrast CMRI. R VIDdiast correlated highly with right ventricular EDV assessed by short-axis and axial CMRI (P < 0.001, P < 0.001). Due to lower intra- and inter-observer variability, axial slices are recommended for right ventricular volumetry in cToF. © The Foundation Acta Radiologica 2014.

Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*.

PubMed

Landesberg, Giora; Jaffe, Allan S; Gilon, Dan; Levin, Phillip D; Goodman, Sergey; Abu-Baih, Abed; Beeri, Ronen; Weissman, Charles; Sprung, Charles L; Landesberg, Amir

2014-04-01

Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Prospective, analytic cohort study. Tertiary academic institute. A cohort of ICU patients with severe sepsis or septic shock. Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e'-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and -2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s'-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e'-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e'-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

Alterations in left ventricular volumes induced by Valsalva manoeuvre

NASA Technical Reports Server (NTRS)

Brooker, J. Z.; Alderman, E. L.; Harrison, D. C.

1974-01-01

Five patients were studied with left ventriculography during different phases of the Valsalva manoeuvre. Small doses of contrast medium allowed adequate repetitive visualization of the left ventricle for volume calculation. During strain phase, the volume of the left ventricle decreased by nearly 50 per cent in each case, and stroke volume and cardiac output also dropped strikingly. Release of straining was attended by a sharp rebound of left ventricular volume to control levels, with a transient surge of increased cardiac output 42 per cent above that of the resting state.

Calsequestrin mutation and catecholaminergic polymorphic ventricular tachycardia: a simulation study of cellular mechanism.

PubMed

Faber, Gregory M; Rudy, Yoram

2007-07-01

Patients with a missense mutation of the calsequestrin 2 gene (CASQ2) are at risk for catecholaminergic polymorphic ventricular tachycardia. This mutation (CASQ2(D307H)) results in decreased ability of CASQ2 to bind Ca2+ in the sarcoplasmic reticulum (SR). In this theoretical study, we investigate a potential mechanism by which CASQ2(D307H) manifests its pro-arrhythmic consequences in patients. Using simulations in a model of the guinea pig ventricular myocyte, we investigate the mutation's effect on SR Ca2+ storage, the Ca2+ transient (CaT), and its indirect effect on ionic currents and membrane potential. We model the effects of isoproterenol (ISO) on Ca(V)1.2 (the L-type Ca2+ current, I(Ca(L))) and other targets of beta-adrenergic stimulation. ISO increases I(Ca(L)), prolonging action potential (AP) duration (Control: 172 ms, +ISO: 207 ms, at cycle length of 1500 ms) and increasing CaT (Control: 0.79 microM, +ISO: 1.61 microM). ISO increases I(Ca(L)) by reducing the fraction of channels which undergo voltage-dependent inactivation and increasing transitions from a non-conducting to conducting mode of channel gating. CASQ2(D307H) reduces SR storage capacity, thereby reducing the magnitude of CaT (Control: 0.79 microM, CASQ2(D307H): 0.52 microM, at cycle length of 1500 ms). The combined effect of CASQ2(D307H) and ISO elevates SR free Ca2+ at a rapid rate, leading to store-overload-induced Ca2+ release and delayed afterdepolarization (DAD). If resting membrane potential is sufficiently elevated, the Na+-Ca2+ exchange-driven DAD can trigger I(Na) and I(Ca(L)) activation, generating a triggered arrhythmogenic AP. The CASQ2(D307H) mutation manifests its pro-arrhythmic consequences due to store-overload-induced Ca2+ release and DAD formation due to excess free SR Ca2+ following rapid pacing and beta-adrenergic stimulation.

Three-dimensional visual guidance improves the accuracy of calculating right ventricular volume with two-dimensional echocardiography

NASA Technical Reports Server (NTRS)

Dorosz, Jennifer L.; Bolson, Edward L.; Waiss, Mary S.; Sheehan, Florence H.

2003-01-01

Three-dimensional guidance programs have been shown to increase the reproducibility of 2-dimensional (2D) left ventricular volume calculations, but these systems have not been tested in 2D measurements of the right ventricle. Using magnetic fields to identify the probe location, we developed a new 3-dimensional guidance system that displays the line of intersection, the plane of intersection, and the numeric angle of intersection between the current image plane and previously saved scout views. When used by both an experienced and an inexperienced sonographer, this guidance system increases the accuracy of the 2D right ventricular volume measurements using a monoplane pyramidal model. Furthermore, a reconstruction of the right ventricle, with a computed volume similar to the calculated 2D volume, can be displayed quickly by tracing a few anatomic structures on 2D scans.

Pressure-volume Relationship in the Stress-echocardiography Laboratory: Does (Left Ventricular End-diastolic) Size Matter?

PubMed

Bombardini, Tonino; Mulieri, Louis A; Salvadori, Stefano; Costantino, Marco Fabio; Scali, Maria Chiara; Marzilli, Mario; Picano, Eugenio

2017-02-01

The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. Whether and to what extent it depends on end-diastolic volume remains unclear. The aim of this study was to assess the dependence of the delta rest-stress end-systolic pressure-volume relation on end-diastolic volume in patients with negative stress echo and all ranges of resting left ventricular function. We analyzed interpretable data obtained in 891 patients (593 men, age 63 ± 12 years) with ejection fraction 47% ± 12%: 338 were normal or near-normal or hypertensive; 229 patients had coronary artery disease; and 324 patients had ischemic or nonischemic dilated cardiomyopathy. They were studied with exercise (n = 172), dipyridamole (n = 482) or dobutamine (n = 237) stress echocardiography. The end-systolic pressure-volume relation was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson rule 2-dimensional echocardiography. Absolute values of delta rest-stress end-systolic pressure-volume relation were higher for exercise and dobutamine than for dipyridamole. In the overall population, an inverse relationship between end-systolic pressure-volume relation and end-diastolic volume was present at rest (r 2 = 0.69, P < .001) and peak stress (r 2 = 0.56, P < .001), but was absent if the delta rest-stress end-systolic pressure-volume relation was considered (r 2 = 0.13). Left ventricular end-diastolic volume does not affect the rest-stress changes in end-systolic pressure-volume relation in either normal or abnormal left ventricles during physical or pharmacological stress. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Intracranial cerebrospinal fluid spaces imaging using a pulse-triggered three-dimensional turbo spin echo MR sequence with variable flip-angle distribution.

PubMed

Hodel, Jérôme; Silvera, Jonathan; Bekaert, Olivier; Rahmouni, Alain; Bastuji-Garin, Sylvie; Vignaud, Alexandre; Petit, Eric; Durning, Bruno; Decq, Philippe

2011-02-01

To assess the three-dimensional turbo spin echo with variable flip-angle distribution magnetic resonance sequence (SPACE: Sampling Perfection with Application optimised Contrast using different flip-angle Evolution) for the imaging of intracranial cerebrospinal fluid (CSF) spaces. We prospectively investigated 18 healthy volunteers and 25 patients, 20 with communicating hydrocephalus (CH), five with non-communicating hydrocephalus (NCH), using the SPACE sequence at 1.5T. Volume rendering views of both intracranial and ventricular CSF were obtained for all patients and volunteers. The subarachnoid CSF distribution was qualitatively evaluated on volume rendering views using a four-point scale. The CSF volumes within total, ventricular and subarachnoid spaces were calculated as well as the ratio between ventricular and subarachnoid CSF volumes. Three different patterns of subarachnoid CSF distribution were observed. In healthy volunteers we found narrowed CSF spaces within the occipital aera. A diffuse narrowing of the subarachnoid CSF spaces was observed in patients with NCH whereas patients with CH exhibited narrowed CSF spaces within the high midline convexity. The ratios between ventricular and subarachnoid CSF volumes were significantly different among the volunteers, patients with CH and patients with NCH. The assessment of CSF spaces volume and distribution may help to characterise hydrocephalus.

Automatically measuring brain ventricular volume within PACS using artificial intelligence.

PubMed

Yepes-Calderon, Fernando; Nelson, Marvin D; McComb, J Gordon

2018-01-01

The picture archiving and communications system (PACS) is currently the standard platform to manage medical images but lacks analytical capabilities. Staying within PACS, the authors have developed an automatic method to retrieve the medical data and access it at a voxel level, decrypted and uncompressed that allows analytical capabilities while not perturbing the system's daily operation. Additionally, the strategy is secure and vendor independent. Cerebral ventricular volume is important for the diagnosis and treatment of many neurological disorders. A significant change in ventricular volume is readily recognized, but subtle changes, especially over longer periods of time, may be difficult to discern. Clinical imaging protocols and parameters are often varied making it difficult to use a general solution with standard segmentation techniques. Presented is a segmentation strategy based on an algorithm that uses four features extracted from the medical images to create a statistical estimator capable of determining ventricular volume. When compared with manual segmentations, the correlation was 94% and holds promise for even better accuracy by incorporating the unlimited data available. The volume of any segmentable structure can be accurately determined utilizing the machine learning strategy presented and runs fully automatically within the PACS.

Continuous Positive Airway Pressure Therapy Reduces Right Ventricular Volume in Patients with Obstructive Sleep Apnea: A Cardiovascular Magnetic Resonance Study

PubMed Central

Magalang, Ulysses J.; Richards, Kathryn; McCarthy, Beth; Fathala, Ahmed; Khan, Meena; Parinandi, Narasimham; Raman, Subha V.

2009-01-01

Study Objectives. There are few data on the effects of continuous positive airway pressure (CPAP) therapy on the structural and functional characteristics of the right heart in patients with obstructive sleep apnea (OSA). We sought to leverage the advantages of cardiac magnetic resonance imaging (CMR) and hypothesized that CPAP treatment would improve right ventricular (RV) function in a group of patients with OSA who were free of other comorbid conditions. Methods. Patients with severe (apnea-hypopnea index ≥ 30/h) untreated OSA were prospectively enrolled. CMR included 3-dimensional measurement of biventricular size and function, and rest/stress myocardial perfusion and was performed at baseline and after 3 months of CPAP therapy. Results. Fifteen patients with mild to moderate desaturation were enrolled; 2 could not undergo CMR due to claustrophobia and obesity. There were significant decreases in the Epworth Sleepiness Scale score (p < 0.0001) and RV end-systolic and RV end-diastolic volumes (p < 0.05) with CPAP. There was a trend toward improvement in RV ejection fraction, but the improvement did not reach statistical significance. Other measures such as left ventricular volumes, left ventricular ejection fraction, myocardial perfusion reserve index, and thickness of the interventricular septum and ventricular free wall did not change significantly. Conclusions: This preliminary study found that CPAP treatment decreases RV volumes in patients with severe OSA who are otherwise healthy. CMR offers a novel technique to determine the effects of CPAP on ventricular structure and function in patients with OSA. A randomized controlled study is needed to confirm the results of our study. Citation: Magalang UJ; Richards K; McCarthy B; Fathala A; Khan M; Parinandi N; Raman SV. Continuous positive airway pressure therapy reduces right ventricular volume in patients with obstructive sleep apnea: a cardiovascular magnetic resonance study. J Clin Sleep Med 2009;5(2):110-114. PMID:19968042

ASSESSMENT OF DIASTOLIC DYSFUNCTION, ARTERIAL STIFFNESS, AND CAROTID INTIMA-MEDIA THICKNESS IN PATIENTS WITH ACROMEGALY.

PubMed

Cansu, Güven Barış; Yılmaz, Nusret; Yanıkoğlu, Atakan; Özdem, Sebahat; Yıldırım, Aytül Belgi; Süleymanlar, Gültekin; Altunbaş, Hasan Ali

2017-05-01

Early diagnosis and treatment of cardiovascular diseases, the most frequent cause of morbidity and mortality in acromegaly, may be an efficient approach to extending the lifespan of affected patients. Therefore, it is crucial to determine any cardiovascular diseases in the subclinical period. The study objectives were to determine markers of subclinical atherosclerosis and asses heart structure and function. This was a cross-sectional, single-center study of 53 patients with acromegaly and 22 age- and sex-matched healthy individuals. Carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and echocardiographic data were compared between these groups. CIMT and PWV were higher in the acromegaly group than in the healthy group (P = .008 and P = .002, respectively). Echocardiography showed that left ventricular diastolic dysfunction was present in 11.3% of patients. Left ventricular mass index and left atrial volume index were higher in the patients (P = .016 and P<.001, respectively). No differences in the CIMT, PWV, or echocardiographic measurements were identified between the patients with biochemically controlled and uncontrolled acromegaly and the control group. Our results showed that subclinical atherosclerosis (i.e., CIMT and PWV markers) and heart structure and function were worse in patients with acromegaly than in healthy individuals. Because there were no differences in these parameters between patients with controlled and uncontrolled acromegaly, our results suggest that the structural and functional changes do not reverse with biochemical control. AA = active acromegaly BSA = body surface area CA = biochemically controlled acromegaly CH = concentric hypertrophy CIMT = carotid intima-media thickness DBP = diastolic blood pressure DM = diabetes mellitus ECHO = echocardiography EDV = enddiastolic volume EF = ejection fraction ESV = endsystolic volume GH = growth hormone HC = healthy control HL = hyperlipidemia HT = hypertension IGF-1 = insulin-like growth factor 1 LA = left atrial LAV = left atrial volume LAVI = left atrial volume index LV = left ventricular LVDD = left ventricular diastolic dysfunction LVEF = left ventricular ejection fraction LVH = left ventricular hypertrophy LVMI = left ventricular mass index PWV = pulse-wave velocity RWT = relative wall thickness.

Hemodynamic responses to external counterbalancing of auto-positive end-expiratory pressure in mechanically ventilated patients with chronic obstructive pulmonary disease.

PubMed

Baigorri, F; de Monte, A; Blanch, L; Fernández, R; Vallés, J; Mestre, J; Saura, P; Artigas, A

1994-11-01

To study the effect of positive end-expiratory pressure (PEEP) on right ventricular hemodynamics and ejection fraction in patients with chronic obstructive pulmonary disease and positive alveolar pressure throughout expiration by dynamic hyperinflation (auto-PEEP). Open, prospective, controlled trial. General intensive care unit of a community hospital. Ten patients sedated and paralyzed with an acute exacerbation of chronic obstructive pulmonary disease undergoing mechanical ventilation. Insertion of a pulmonary artery catheter modified with a rapid response thermistor and a radial arterial catheter. PEEP was then increased from 0 (PEEP 0) to auto-PEEP level (PEEP = auto-PEEP) and 5 cm H2O above that (PEEP = auto-PEEP +5). At each level of PEEP, airway pressures, flow and volume, hemodynamic variables (including right ventricular ejection fraction by thermodilution technique), and blood gas analyses were recorded. The mean auto-PEEP was 6.6 +/- 2.8 cm H2O and the total PEEP reached was 12.2 +/- 2.4 cm H2O. The degree of lung inflation induced by PEEP averaged 145 +/- 87 mL with PEEP = auto-PEEP and 495 +/- 133 mL with PEEP = auto-PEEP + 5. The PEEP = auto-PEEP caused a right ventricular end-diastolic pressure increase, but there was no other significant hemodynamic change. With PEEP = auto-PEEP + 5, there was a significant increase in intravascular pressures; this amount of PEEP reduced cardiac output (from 4.40 +/- 1.38 L/min at PEEP 0 to 4.13 +/- 1.48 L/min; p < .05). The cardiac output reduction induced by PEEP = auto-PEEP + 5 was > 10% in only five cases and this group of patients had significantly lower right ventricular volumes than the group with less cardiac output variation (right ventricular end-diastolic volume: 64 +/- 9 vs. 96 +/- 26 mL/m2; right ventricular end-systolic volume: 38 +/- 6 vs. 65 +/- 21 mL/m2; p < .05) without significant difference in the other variables that were measured. Neither right ventricular ejection fraction nor right ventricle volumes changed as PEEP increased, but there were marked interpatient differences and also pronounced changes in volume between stages in individual patients. In the study conditions, PEEP application up to values approaching auto-PEEP did not result in the impairment of right ventricular hemodynamics, while higher levels reduced cardiac output in selected patients.

"Pulmonary valve replacement diminishes the presence of restrictive physiology and reduces atrial volumes": a prospective study in Tetralogy of Fallot patients.

PubMed

Pijuan-Domenech, Antonia; Pineda, Victor; Castro, Miguel Angel; Sureda-Barbosa, Carlos; Ribera, Aida; Cruz, Luz M; Ferreira-Gonzalez, Ignacio; Dos-Subirà, Laura; Subirana-Domènech, Teresa; Garcia-Dorado, David; Casaldàliga-Ferrer, Jaume

2014-11-15

Pulmonary valve replacement (PVR) reduces right ventricular (RV) volumes in the setting of long-term pulmonary regurgitation after Tetralogy of Fallot (ToF) repair; however, little is known of its effect on RV diastolic function. Right atrial volumes may reflect the burden of RV diastolic dysfunction. The objective of this paper is to evaluate the clinical, echocardiographic, biochemical and cardiac magnetic resonance (CMR) variables, focusing particularly on right atrial response and right ventricular diastolic function prior to and after elective PVR in adult patients with ToF. This prospective study was conducted from January 2009 to April 2013 in consecutive patients > 18 years of age who had undergone ToF repair in childhood and were accepted for elective PVR. Twenty patients (mean age: 35 years; 70% men) agreed to enter the study. PVR was performed with a bioporcine prosthesis. Concomitant RV reduction was performed in all cases when technically possible. Pulmonary end-diastolic forward flow (EDFF) decreased significantly from 5.4 ml/m(2) to 0.3 ml/m(2) (p < 0.00001), and right atrial four-chamber echocardiographic measurements and volumes by 25% (p = 0.0024): mean indexed diastolic/systolic atrial volumes prior to surgery were 43 ml/m(2) (SD+/-4.6)/63 ml/m(2) (SD+/-5.5), and dropped to 33 ml/m(2) (SD+/-3)/46 ml/m(2) (SD+/-2.55) post-surgery. All patients presented right ventricular diastolic and systolic volume reductions, with a mean volume reduction of 35% (p < 0.00001). Right ventricular diastolic dysfunction was common in a population of severely dilated RV patients long term after ToF repair. Right ventricular diastolic parameters improved as did right atrial volumes in keeping with the known reduction in RV volumes, after PVR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Ventricular efficiency in pregnant women with congenital heart disease.

PubMed

Muneuchi, Jun; Yamasaki, Keiko; Watanabe, Mamie; Fukumitsu, Azusa; Kawakami, Takeshi; Nakahara, Hiromasa; Joo, Kunitaka

2018-06-15

Pregnant women with congenital heart disease (CHD) are at risk of cardiovascular events during pregnancy as well as postpartum. The aim of our study is to address the feasibility of echocardiography-derived ventricular-arterial coupling during pregnancy and postpartum among women with CHD. In 31 pregnant women with CHD, we performed serial echocardiography at the first and third trimesters, early and late postpartum. The indices of contractility (single-beat determined end-systolic elastance, Ees ab ) and afterload (effective arterial elastance, Ea) were approximated on the basis of the systemic blood pressure and systemic ventricular volume. The ratio of stroke work and pressure-volume area (SW/PVA) representing ventricular efficiency was also calculated. Age at the delivery was 28 (24-31) years. ZAHARA score was 0.75 (0.75-1.50). Gestational age and birth weight of newborns were 38 (37-39) weeks and 2.73 (2.42-2.92) kg, respectively. Heart rate, systemic ventricular end-diastolic volume and stroke volume significantly increased from the first trimester to the third trimester and reversed postpartum to the values of the first trimester. Ees ab and Ea significantly decreased from the first trimester to the third trimester (Ees ab ; 4.90 [2.86-7.14] vs 3.41 [2.53-4.61] mm Hg/ml, p = 0.0001, Ea; 2.83 [1.74-3.30] vs 2.18 [1.67-2.68] mm Hg/ml, p = 0.0012), and reversed early postpartum parallelly. Ejection fraction and SW/PVA remained unchanged throughout pregnancy and postpartum. Echocardiography-derived ventricular-arterial coupling is feasible to understand ventricular function in pregnant women with CHD. Copyright © 2018 Elsevier B.V. All rights reserved.

The Impact of a Targeted Training Program on E-Mail System Processing Capabilities and Self-Perception of E-Mail Overload

ERIC Educational Resources Information Center

Einstein, Michael M.

2014-01-01

As business e-mail volumes continue to grow and employees spend increasingly larger portions of their day processing e-mail, there is strong evidence of the negative impacts of e-mail processing, especially with respect to e-mail overload. This study sought to determine whether a training program focused on select e-mail features and processing…

Coupling of a 3D Finite Element Model of Cardiac Ventricular Mechanics to Lumped Systems Models of the Systemic and Pulmonic Circulation

PubMed Central

Kerckhoffs, Roy C. P.; Neal, Maxwell L.; Gu, Quan; Bassingthwaighte, James B.; Omens, Jeff H.; McCulloch, Andrew D.

2010-01-01

In this study we present a novel, robust method to couple finite element (FE) models of cardiac mechanics to systems models of the circulation (CIRC), independent of cardiac phase. For each time step through a cardiac cycle, left and right ventricular pressures were calculated using ventricular compliances from the FE and CIRC models. These pressures served as boundary conditions in the FE and CIRC models. In succeeding steps, pressures were updated to minimize cavity volume error (FE minus CIRC volume) using Newton iterations. Coupling was achieved when a predefined criterion for the volume error was satisfied. Initial conditions for the multi-scale model were obtained by replacing the FE model with a varying elastance model, which takes into account direct ventricular interactions. Applying the coupling, a novel multi-scale model of the canine cardiovascular system was developed. Global hemodynamics and regional mechanics were calculated for multiple beats in two separate simulations with a left ventricular ischemic region and pulmonary artery constriction, respectively. After the interventions, global hemodynamics changed due to direct and indirect ventricular interactions, in agreement with previously published experimental results. The coupling method allows for simulations of multiple cardiac cycles for normal and pathophysiology, encompassing levels from cell to system. PMID:17111210

Diastolic function of the nonfilling human left ventricle.

PubMed

Paulus, W J; Vantrimpont, P J; Rousseau, M F

1992-12-01

To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice. When mitral inflow was impeded in anesthetized dogs, left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect. Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon. The left ventricular diastolic asymptote pressure (P(asy)) was determined in 47 nonfilling beats with a sufficiently long (greater than 200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 +/- 3 mm Hg for beats with normal intraventricular conduction and 3 +/- 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 +/- 14 ml and was comparable to the left ventricular end-systolic volume (39 +/- 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval greater than 200 ms, normal intraventricular conduction and peak left ventricular pressure greater than 50 mm Hg. Time constants (T0 and TBF) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a time constant (T(asy)) derived from an exponential curve fit with the measured diastolic left ventricular asymptote pressure. The value for T(asy) (37 +/- 9 ms) was significantly smaller than that for TBF (68 +/- 28 ms, p less than 0.001) and the value for the measured diastolic left ventricular asymptote pressure (2 +/- 4 mm Hg) was significantly larger than that for the best-fit asymptote pressure (-9 +/- 11 mm Hg, p less than 0.001). T0 (44 +/- 20 ms) was significantly (p less than 0.01) different from TBF but not from T(asy). During balloon inflation of a self-positioning Inoue balloon, left ventricular pressure decayed continuously toward a positive asymptote value and left ventricular cavity volume was comparable to the left ventricular end-systolic volume of filling beats. In these nonfilling beats, the best-fit asymptote pressure was unrelated to the measured asymptote pressure and T0 was a better measure of T(asy) than was TBF. Reduced internal myocardial restoring forces, caused by different extracellular matrix of the human heart, reduced external myocardial restoring forces caused by low coronary perfusion pressure during the balloon inflation and inward motion of the balloon-occluded mitral valve into the left ventricular cavity could explain the failure to observe significant diastolic left ventricular suction in the human heart.

Dependence of intramyocardial pressure and coronary flow on ventricular loading and contractility: a model study.

PubMed

Bovendeerd, Peter H M; Borsje, Petra; Arts, Theo; van De Vosse, Frans N

2006-12-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity.

Echocardiographic measurements of left ventricular mass by a non-geometric method

NASA Technical Reports Server (NTRS)

Parra, Beatriz; Buckey, Jay; Degraff, David; Gaffney, F. Andrew; Blomqvist, C. Gunnar

1987-01-01

The accuracy of a new nongeometric method for calculating left ventricular myocardial volumes from two-dimensional echocardiographic images was assessed in vitro using 20 formalin-fixed normal human hearts. Serial oblique short-axis images were acquired from one point at 5-deg intervals, for a total of 10-12 cross sections. Echocardiographic myocardial volumes were calculated as the difference between the volumes defined by the epi- and endocardial surfaces. Actual myocardial volumes were determined by water displacement. Volumes ranged from 80 to 174 ml (mean 130.8 ml). Linear regression analysis demonstrated excellent agreement between the echocardiographic and direct measurements.

Changes in mitral annular and left ventricular dimensions and left ventricular pressure-volume relations after off-pump treatment of mitral regurgitation with the Coapsys device.

PubMed

Fukamachi, Kiyotaka; Popović, Zoran B; Inoue, Masahiro; Doi, Kazuyoshi; Schenk, Soren; Ootaki, Yoshio; Kopcak, Michael W; McCarthy, Patrick M

2004-03-01

The objective of this study was to evaluate the changes in mitral annular and left ventricular dimensions and left ventricular pressure-volume relations produced by the Myocor Coapsys device that has been developed to treat functional mitral regurgitation (MR) off-pump. The Coapsys device, which consists of anterior and posterior epicardial pads connected by a sub-valvular chord, was implanted in seven dogs with functional MR resulting from pacing induced cardiomyopathy. The Coapsys device was then sized by drawing the posterior leaflet and annulus toward the anterior leaflet. During sizing, MR grade was assessed using color flow Doppler echocardiography. Final device size was selected when MR was eliminated or minimized. Following implantation, heart failure was maintained by continued pacing for a period of 8 weeks. Mitral annular and left ventricular dimensions and left ventricular pressure-volume relations were evaluated by two-dimensional echocardiography and a conductance catheter, respectively, at pre-sizing, post-sizing, and after 8 weeks. All implants were performed on beating hearts without cardiopulmonary bypass. Mean MR grade was reduced from 2.9+/-0.7 at pre-sizing to 0.7+/-0.8 at post-sizing (P<0.001), and was maintained at 0.8+/-0.8 after 8 weeks (P<0.01). The septal-lateral dimensions were significantly reduced at both mitral annular level [2.4+/-0.2 cm at pre-sizing, 1.5+/-0.3 cm at post-sizing (P<0.001) and 1.8+/-0.3 cm after 8 weeks (P<0.05)] and mid-papillary level [4.1+/-0.4 cm at pre-sizing, 2.4+/-0.2 cm at post-sizing (P<0.001) and 3.3+/-0.4 cm after 8 weeks (P<0.001)]. The end-systolic pressure-volume relation shifted leftward at post-sizing with a significantly steeper slope (P=0.03). There was a significant (P=0.03) leftward shift of the end-diastolic pressure-volume relation at post-sizing. After 8 weeks, these changes in pressure-volume relations tended to return to pre-sizing relations. The Coapsys device significantly reduced MR by treating both the mitral annular dilatation and the papillary muscle displacement. Despite these significant dimensional changes, the Coapsys device did not negatively affect the left ventricular pressure-volume relations.

Importance of Non-invasive Right and Left Ventricular Variables on Exercise Capacity in Patients with Tetralogy of Fallot Hemodynamics.

PubMed

Meierhofer, Christian; Tavakkoli, Timon; Kühn, Andreas; Ulm, Kurt; Hager, Alfred; Müller, Jan; Martinoff, Stefan; Ewert, Peter; Stern, Heiko

2017-12-01

Good quality of life correlates with a good exercise capacity in daily life in patients with tetralogy of Fallot (ToF). Patients after correction of ToF usually develop residual defects such as pulmonary regurgitation or stenosis of variable severity. However, the importance of different hemodynamic parameters and their impact on exercise capacity is unclear. We investigated several hemodynamic parameters measured by cardiovascular magnetic resonance (CMR) and echocardiography and evaluated which parameter has the most pronounced effect on maximal exercise capacity determined by cardiopulmonary exercise testing (CPET). 132 patients with ToF-like hemodynamics were tested during routine follow-up with CMR, echocardiography and CPET. Right and left ventricular volume data, ventricular ejection fraction and pulmonary regurgitation were evaluated by CMR. Echocardiographic pressure gradients in the right ventricular outflow tract and through the tricuspid valve were measured. All data were classified and correlated with the results of CPET evaluations of these patients. The analysis was performed using the Random Forest model. In this way, we calculated the importance of the different hemodynamic variables related to the maximal oxygen uptake in CPET (VO 2 %predicted). Right ventricular pressure showed the most important influence on maximal oxygen uptake, whereas pulmonary regurgitation and right ventricular enddiastolic volume were not important hemodynamic variables to predict maximal oxygen uptake in CPET. Maximal exercise capacity was only very weakly influenced by right ventricular enddiastolic volume and not at all by pulmonary regurgitation in patients with ToF. The variable with the most pronounced influence was the right ventricular pressure.

Effect of prolonged space flight on cardiac function and dimensions

NASA Technical Reports Server (NTRS)

Henry, W. L.; Epstein, S. E.; Griffith, J. M.; Goldstein, R. E.; Redwood, D. R.

1974-01-01

Echocardiographic studies were performed preflight 5 days before launch and on recovery day and 1, 2, 4, 11, 31 and 68 days postflight. From these echocardiograms measurements were made. From these primary measurements, left ventricular end-diastolic volume, end-systolic volume, stroke volume, and mass were derived using the accepted assumptions. Findings in the Scientist Pilot and Pilot resemble those seen in trained distance runners. Wall thickness measurements were normal in all three crewmembers preflight. Postflight basal studies were unchanged in the Commander on recovery day through 68 days postflight in both the Scientist Pilot and Pilot, however, the left ventricular end-diastolic volume, stroke volume, and mass were decreased slightly. Left ventricular function curves were constructed for the Commander and Pilot by plotting stroke volume versus end-diastolic volume. In both astronauts, preflight and postflight data fell on the same straight line demonstrating that no deterioration in cardiac function had occurred. These data indicate that the cardiovascular system adapts well to prolonged weightlessness and suggest that alterations in cardiac dimensions and function are unlikely to limit man's future in space.

76 FR 48563 - Medicare and Medicaid Programs; Quarterly Listing of Program Issuances-January Through March 2011...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

...-7205 Ventricular Assist Device (Destination Therapy) Facilities. XIII Medicare-Approved Lung JoAnna...-Approved Ventricular Assist Device (Destination Therapy) Facilities, Addendum XIII: Lung Volume Reduction...-Approved Ventricular Assist Device (Destination Therapy) Facilities (January Through March 2011) Addendum...

Is Doppler tissue velocity during early left ventricular filling preload independent?

NASA Technical Reports Server (NTRS)

Yalcin, F.; Kaftan, A.; Muderrisoglu, H.; Korkmaz, M. E.; Flachskampf, F.; Garcia, M.; Thomas, J. D.

2002-01-01

BACKGROUND: Transmitral Doppler flow indices are used to evaluate diastolic function. Recently, velocities measured by Doppler tissue imaging have been used as an index of left ventricular relaxation. OBJECTIVE: To determine whether Doppler tissue velocities are influenced by alterations in preload. METHODS: Left ventricular preload was altered in 17 patients (all men, mean (SD) age, 49 (8) years) during echocardiographic measurements of left ventricular end diastolic volume, maximum left atrial area, peak early Doppler filling velocity, and left ventricular myocardial velocities during early filling. Preload altering manoeuvres included Trendelenberg (stage 1), reverse Trendelenberg (stage 2), and amyl nitrate (stage 3). Systolic blood pressure was measured at each stage. RESULTS: In comparison with baseline, left ventricular end diastolic volume (p = 0.001), left atrial area (p = 0.003), peak early mitral Doppler filling velocity (p = 0.01), and systolic blood pressures (p = 0.001) were all changed by preload altering manoeuvres. Only left ventricular myocardial velocity during early filling remained unchanged by these manoeuvres. CONCLUSIONS: In contrast to standard transmitral Doppler filling indices, Doppler tissue early diastolic velocities are not significantly affected by physiological manoeuvres that alter preload. Thus Doppler tissue velocities during early left ventricular diastole may provide a better index of diastolic function in cardiac patients by providing a preload independent assessment of left ventricular filling.

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.

Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs.

PubMed

Honda, Atsushi; Nakamura, Yuji; Ohara, Hiroshi; Cao, Xin; Nomura, Hiroaki; Katagi, Jun; Wada, Takeshi; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Sugiyama, Atsushi

2016-03-15

Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4-5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 µg/kg/min for 10 min, dobutamine in a dose of 1 µg/kg/min for 10 min and milrinone in a dose of 5 µg/kg/min for 10 min followed by 0.5 µg/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end-diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO-AE1-329 increased the heart rate and maximum elastance, but decreased the end-systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction. Copyright © 2016 Elsevier B.V. All rights reserved.

Dissociation of end systole from end ejection in patients with long-term mitral regurgitation.

PubMed

Brickner, M E; Starling, M R

1990-04-01

To determine whether left ventricular (LV) end systole and end ejection uncouple in patients with long-term mitral regurgitation, 59 patients (22 control patients with atypical chest pain, 21 patients with aortic regurgitation, and 16 patients with mitral regurgitation) were studied with micromanometer LV catheters and radionuclide angiograms. End systole was defined as the time of occurrence (Tmax) of the maximum time-varying elastance (Emax), and end ejection was defined as the time of occurrence of minimum ventricular volume (minV) and zero systolic flow as approximated by the aortic dicrotic notch (Aodi). The temporal relation between end systole and end ejection in the control patients was Tmax (331 +/- 42 [SD] msec), minV (336 +/- 36 msec), and then, zero systolic flow (355 +/- 23 msec). This temporal relation was maintained in the patients with aortic regurgitation. In contrast, in the patients with mitral regurgitation, the temporal relation was Tmax (266 +/- 49 msec), zero systolic flow (310 +/- 37 msec, p less than 0.01 vs. Tmax), and then, minV (355 +/- 37 msec, p less than 0.001 vs. Tmax and p less than 0.01 vs. Aodi). Additionally, the average Tmax occurred earlier in the patients with mitral regurgitation than in the control patients and patients with aortic regurgitation (p less than 0.01, for both), whereas the average time to minimum ventricular volume was similar in all three patient groups. Moreover, the average time to zero systolic flow also occurred earlier in the patients with mitral regurgitation than in the control patients (p less than 0.01) and patients with aortic regurgitation (p less than 0.05). Because of the dissociation of end systole from minimum ventricular volume in the patients with mitral regurgitation, the end-ejection pressure-volume relations calculated at minimum ventricular volume did not correlate (r = -0.09), whereas those calculated at zero systolic flow did correlate (r = 0.88) with the Emax slope values. We conclude that end ejection, defined as minimum ventricular volume, dissociates from end systole in patients with mitral regurgitation because of the shortened time to LV end systole in association with preservation of the time to LV end ejection due to the low impedance to ejection presented by the left atrium. Therefore, pressure-volume relations calculated at minimum ventricular volume might not be useful for assessing LV chamber performance in some patients with mitral regurgitation.

Fornix Under Water? Ventricular Enlargement Biases Forniceal Diffusion Magnetic Resonance Imaging Indices in Anorexia Nervosa.

PubMed

Kaufmann, Lisa-Katrin; Baur, Volker; Hänggi, Jürgen; Jäncke, Lutz; Piccirelli, Marco; Kollias, Spyros; Schnyder, Ulrich; Pasternak, Ofer; Martin-Soelch, Chantal; Milos, Gabriella

2017-07-01

Acute anorexia nervosa (AN) is characterized by reduced brain mass and corresponding increased sulcal and ventricular cerebrospinal fluid. Recent studies of white matter using diffusion tensor imaging consistently identified alterations in the fornix, such as reduced fractional anisotropy (FA). However, because the fornix penetrates the ventricles, it is prone to cerebrospinal fluid-induced partial volume effects that interfere with a valid assessment of FA. We investigated the hypothesis that in the acute stage of AN, FA of the fornix is markedly affected by ventricular volumes. First, using diffusion tensor imaging data we established the inverse associations between forniceal FA and volumes of the third and lateral ventricles in a prestudy with 32 healthy subjects to demonstrate the strength of ventricular influence on forniceal FA independent of AN. Second, we investigated a sample of 25 acute AN patients and 25 healthy control subjects. Using ventricular volumes as covariates markedly reduced the group effect of forniceal FA, even with tract-based spatial statistics focusing only on the center of the fornix. In addition, after correcting for free water on voxel level, the group differences in forniceal FA between AN patients and controls disappeared completely. It is unlikely that microstructural changes affecting FA occurred in the fornix of AN patients. Previously identified alterations in acute AN may have been biased by partial volume effects and the proposed central role of this structure in the pathophysiology may need to be reconsidered. Future studies on white matter alterations in AN should carefully deal with partial volume effects. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Do we overestimate left ventricular ejection fraction by two-dimensional echocardiography in patients with left bundle branch block?

PubMed

Cabuk, Ali K; Cabuk, Gizem; Sayin, Ahmet; Karamanlioglu, Murat; Kilicaslan, Barış; Ekmekci, Cenk; Solmaz, Hatice; Aslanturk, Omer F; Ozdogan, Oner

2018-02-01

Left bundle branch block (LBBB) causes a dyssynchronized contraction of left ventricle. This is a kind of regional wall-motion abnormality and measuring left ventricular ejection fraction (LVEF) by two-dimensional (2D) echocardiography could be less reliable in this particular condition. Our aim was to evaluate the role of dyssynchrony index (SDI), measured by three-dimensional (3D) echocardiography, in assessment of LVEF and left ventricular volumes accurately in patients with LBBB. In this case-control study, we included 52 of 64 enrolled participants (twelve participants with poor image quality were excluded) with LBBB and normal LVEF or nonischemic cardiomyopathy. Left ventricular ejection fraction (LVEF) and left ventricular volumes were assessed by 2D (modified Simpson's rule) and 3D (four beats full volume analysis) echocardiography and the impact of SDI on results were evaluated. In patients with SDI ≥6%, LVEF measurements were significantly different (46.00% [29.50-52.50] vs 37.60% [24.70-45.15], P < .001) between 2D and 3D echocardiography, respectively. In patients with SDI < 6%, there were no significant differences between two modalities in terms of LVEF measurements (54.50% [49.00-59.00] vs 54.25% [40.00-58.25], P = .193). LV diastolic volumes were not significantly different while systolic volumes were underestimated by 2D echocardiography, and this finding was more pronounced when SDI ≥ 6%. In patients with LBBB and high SDI (≥6%), LVEF values were overestimated and systolic volumes were underestimated by 2D echocardiography compared to 3D echocardiography. © 2017 Wiley Periodicals, Inc.

The Electrophysiologic Effects of Acute Mitral Regurgitation in a Canine Model.

PubMed

Lawrance, Christopher P; Henn, Matthew C; Miller, Jacob R; Kopek, Michael A; Zhang, Andrew J; Schuessler, Richard B; Damiano, Ralph J

2017-04-01

Atrial fibrillation (AF) occurs in 30% of patients with mitral regurgitation referred for surgical intervention. However, the underlying mechanisms in this population are poorly understood. This study examined the effects of acute left atrial volume overload on atrial electrophysiology and the inducibility of AF. Ten canines underwent insertion of an atrioventricular shunt between the left ventricle and left atrium. Shunt and aortic flows were calculated, and the shunt was titrated to a shunt fraction to 40% to 50% of cardiac output. An epicardial plaque with 250 bipolar electrodes was used to determine activation and refractory periods. Biatrial pressures and volumes, conduction times, and atrial fibrillation inducibility were recorded. Data were collected at baseline and 20 minutes after shunt opening and closure. Mean shunt flow was 1.3 ± 0.5 L/min with a shunt fraction of 43% ± 6% simulating moderate to severe mitral regurgitation. Compared with baseline, left atrial volumes and maximum pressures increased by 27% and 29%, respectively, after shunt opening. Biatrial effective refractory periods did not change significantly after shunt opening or closure. Conduction times increased by 9% with shunt opening and returned to baseline after closure. AF duration or inducibility did not change with shunt opening. This canine model of mitral regurgitation demonstrated that acute left atrial volume overload did not increase the inducibility of atrial arrhythmias in contrast with experimental and clinical findings of chronic left atrial volume overload. This suggests that the substrates for AF in patients with mitral regurgitation are a result of chronic remodeling. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Right ventriculography as a valid method for the diagnosis of tricuspid insufficiency.

PubMed

Ubago, J L; Figueroa, A; Colman, T; Ochoteco, A; Rodríguez, M; Durán, C M

1981-01-01

The value of right ventriculography in the diagnosis of tricuspid insufficiency (TI) is often questioned because of 1) the high incidence of premature ventricular contractions (PVCs) during injections and 2) interference of the catheter in the valve closure mechanism. In 168 patients a commercially available, not preshaped, balloon-tipped catheter was used for right ventriculography. To avoid the induction of PVCs, the catheter tip was placed in the middle third of the diafragmatic wall of the right ventricle, and the balloon was inflated, becoming trapped by the trabeculae. In this position the catheter's side holes should be located in the inflow chamber. To ensure this correct position, and therefore lack of ectopic beats during angiography, a saline test injection was performed previously in every case. With this technique the incidence of PVCs during ventriculography was only 7.7%. In all but one case, such beats were isolated. The 168 patients were divided into three groups according to their likelihood of experiencing tricuspid interference by the catheter: group 1 included 41 patients with a normal heart or with coronary artery disease. No one from this group had TI. Of group II, 28 patients with right ventricular pressure or volume overload or cardiomyopathy, only 2 had TI, both with a previous clinical diagnosis of regurgitation. Group III contained 99 patients with rheumatic heart disease. Thirty-five of them showed angiographic TI, and 24 of these had this diagnosis confirmed either clinically or at surgery. It is felt that this technique of right ventriculography, with its low incidence of PVCs and slight interference with tricuspid closure, is a valid method for the objective study of the tricuspid valve.

Role of Left Ventricular Diastolic Dysfunction in Predicting Atrial Fibrillation Recurrence after Successful Electrical Cardioversion

PubMed Central

Melduni, Rowlens M.; Cullen, Michael W.

2013-01-01

The role of left ventricular (LV) diastolic dysfunction in predicting atrial fibrillation (AF) recurrence after successful electrical cardioversion is largely unknown. Studies suggest that there may be a link between abnormal LV compliance and the initial development, and recurrence of AF after electrical cardioversion. Although direct-current cardioversion (DCCV) is a well-established and highly effective method to convert AF to sinus rhythm, it offers little else beyond immediate rate control because it does not address the underlying cause of AF. Preservation of sinus rhythm after successful cardioversion still remains a challenge for clinicians. Despite the use of antiarrhythmic drugs and serial cardioversions, the rate of AF recurrence remains high in the first year. Current evidence suggests that diastolic dysfunction, which is associated with atrial volume and pressure overload, may be a mechanism underlying the perpetuating cycle of AF recurrence following successful electrical cardioversion. Diastolic dysfunction is considered to be a defect in the ability of the myofibrils, which have shortened against a load in systole to eject blood into the high-pressure aorta, to rapidly or completely return to their resting length. Consequently, LV filling is impaired and the non-compliant left ventricle is unable to fill at low pressures. As a result, left atrial and pulmonary vein pressure rises, and electrical and structural remodeling of the atrial myocardium ensues, creating a vulnerable substrate for AF. In this article, we review the current evidence highlighting the association of LV diastolic dysfunction with AF recurrence after successful electrical cardioversion and provide an approach to the management of LV diastolic dysfunction to prevent AF recurrence. PMID:23525127

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.

Impact of 30 Day Readmission After Left Ventricular Assist Device Implantation.

PubMed

Gupta, Saurabh; Cogswell, Rebecca J; Roy, Samit S; Spratt, John R; Liao, Kenneth K; Martin, Cindy M; John, Ranjit

2018-05-07

Early readmission (within 30 days) after left ventricular assist device (LVAD) implantation might be a marker for increased mortality. We retrospectively reviewed the records of 277 adults who underwent continuous-flow LVAD implantation from 2005 through 2015 at our institution. The baseline characteristics of patients who were (versus were not) readmitted within 30 days after LVAD implantation were compared. To assess the impact of 30 day readmission on long-term survival, we used multivariate Cox regression. We also compared the cardiac transplant rate between the two groups. Of the 277 patients, 217 (78.3%) underwent LVAD implantation as a bridge-to-transplant; 76 (27.4%) of the 277 were readmitted within 30 days. The most common reason for readmission was volume overload (23.6%), followed by gastrointestinal bleeding (15.8%). Male gender, previous smoking, a higher baseline creatinine level, higher Model for End Stage Liver Disease Excluding INR (MELD-XI) score, and postoperative gastrointestinal bleeding or stroke were each associated with 30 day readmission. In our final multivariate model, increased mortality was also associated with 30 day readmission (hazard ratio, 1.60; 95% confidence interval, 1.1-2.5). Among the 217 bridge-to-transplant patients, the cardiac transplant rate was similar between the two groups: 18.7 transplants per patient-year among those who were readmitted within 30 days versus 19.7 transplants per patient-year among those who were not (p = 0.26). Among our study patients, 30 day readmission after LVAD implantation was frequent and was associated with increased mortality. It is currently unclear whether the general health of those patients was a factor and whether efforts to reduce 30 day readmission would favorably affect longer-term patient outcomes.

SOCS3

PubMed Central

Yasukawa, Hideo; Nagata, Takanobu; Oba, Toyoharu; Imaizumi, Tsutomu

2012-01-01

The suppressors of cytokine signaling (SOCS) family of proteins are cytokine-inducible inhibitors of Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) signaling pathways. Among the family, SOCS1 and SOCS3 potently suppress cytokine actions by inhibiting JAK kinase activities. The generation of mice lacking individual SOCS genes has been instrumental in defining the role of individual SOCS proteins in specific cytokine pathways in vivo; SOCS1 is an essential negative regulator of interferon-γ (IFNγ) and SOCS3 is an essential negative regulator of leukemia inhibitory factor (LIF). JAK-STAT3 activating cytokines have exhibited cardioprotective roles in the heart. The cardiac-specific deletion of SOCS3 enhances the activation of cardioprotective signaling pathways, inhibits myocardial apoptosis and fibrosis and results in the inhibition of left ventricular remodeling after myocardial infarction (MI). We propose that myocardial SOCS3 is a key determinant of left ventricular remodeling after MI, and SOCS3 may serve as a novel therapeutic target to prevent left ventricular remodeling after MI. In this review, we discuss the signaling pathways mediated by JAK-STAT and SOCS proteins and their roles in the development of myocardial injury under stress (e.g., pressure overload, viral infection and ischemia). PMID:24058778

Age-related differences in the structural complexity of subcortical and ventricular structures.

PubMed

Madan, Christopher R; Kensinger, Elizabeth A

2017-02-01

It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18-94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload.

PubMed

Fetterman, Jessica L; Zelickson, Blake R; Johnson, Larry W; Moellering, Douglas R; Westbrook, David G; Pompilius, Melissa; Sammy, Melissa J; Johnson, Michelle; Dunham-Snary, Kimberly J; Cao, Xuemei; Bradley, Wayne E; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G; Kesterson, Robert A; Dell'italia, Louis J; Darley-Usmar, Victor M; Welch, Danny R; Ballinger, Scott W

2013-10-15

Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial-nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the 'mitochondrial paradigm' for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress.

Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

PubMed Central

Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.; Kesterson, Robert A.; Dell’Italia, Louis J.; Darley-Usmar, Victor M.; Welch, Danny R.; Ballinger, Scott W.

2013-01-01

Synopsis Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harboring the C57/BL6J mtDNA generate more reactive oxygen species (ROS) and have a higher mitochondrial membrane potential relative to those having the C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the “mitochondrial paradigm” for the development of disease susceptibility, and show that the mtDNA modulates, cellular bioenergetics, mitochondrial reactive oxygen species generation and susceptibility to cardiac stress. PMID:23924350

Performance analysis of SS7 congestion controls under sustained overload

NASA Astrophysics Data System (ADS)

Manfield, David R.; Millsteed, Gregory K.; Zukerman, Moshe

1994-04-01

Congestion controls are a key factor in achieving the robust performance required of common channel signaling (CCS) networks in the face of partial network failures and extreme traffic loads, especially as networks become large and carry high traffic volume. The CCITT recommendations define a number of types of congestion control, and the parameters of the controls must be well set in order to ensure their efficacy under transient and sustained signalling network overload. The objective of this paper is to present a modeling approach to the determination of the network parameters that govern the performance of the SS7 congestion controls under sustained overload. Results of the investigation by simulation are presented and discussed.

High and Low Salt Intake during Pregnancy: Impact on Cardiac and Renal Structure in Newborns.

PubMed

Seravalli, Priscila; de Oliveira, Ivone Braga; Zago, Breno Calazans; de Castro, Isac; Veras, Mariana Matera; Alves-Rodrigues, Edson Nogueira; Heimann, Joel C

2016-01-01

Previous studies from our laboratory demonstrated that dietary salt overload and salt restriction during pregnancy were associated with cardiac and renal structural and/or functional alterations in adult offspring. The present study evaluated renal and cardiac structure and the local renin-angiotensin system in newborns from dams fed high-, normal- or low-salt diets during pregnancy. Female Wistar rats were fed low- (LS, 0.15% NaCl), normal- (NS, 1.3% NaCl) or high- (HS, 8% NaCl) salt diets during pregnancy. Kidneys and hearts were collected from newborns (n = 6-8/group) during the first 24 hours after birth to evaluate possible changes in structure using stereology. Protein expression of renin-angiotensin system components was evaluated using an indirect enzyme-linked immunosorbent assay (ELISA). No differences between groups were observed in total renal volume, volume of renal compartments or number of glomeruli. The transverse diameter of the nuclei of cardiomyocytes was greater in HS than NS males in the left and right ventricles. Protein expression of the AT1 receptor was lower in the kidneys of the LS than in those of the NS and HS males but not females. Protein expression of the AT2 receptor was lower in the kidneys of the LS males and females than in those of the NS males and females. High salt intake during pregnancy induced left and right ventricular hypertrophy in male newborns. Salt restriction during pregnancy reduced the expression of renal angiotensin II receptors in newborns.

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure.

PubMed

Barkoudah, Ebrahim; Kodali, Sindhura; Okoroh, Juliet; Sethi, Rosh; Hulten, Edward; Suemoto, Claudia; Bittencourt, Marcio Sommer

2015-05-01

Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): -2.65 to -0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = -0.25 mg/dL; 95% CI: -0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64-1.56; p = 0.993). Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed.

Meta-Analysis of Ultrafiltration versus Diuretics Treatment Option for Overload Volume Reduction in Patients with Acute Decompensated Heart Failure

PubMed Central

Barkoudah, Ebrahim; Kodali, Sindhura; Okoroh, Juliet; Sethi, Rosh; Hulten, Edward; Suemoto, Claudia; Bittencourt, Marcio Sommer

2015-01-01

Introduction Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. Objective The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. Results A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): −2.65 to −0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = −0.25 mg/dL; 95% CI: −0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64–1.56; p = 0.993). Conclusion Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed. PMID:25626761

Clinical application of a light-pen computer system for quantitative angiography

NASA Technical Reports Server (NTRS)

Alderman, E. L.

1975-01-01

The paper describes an angiographic analysis system which uses a video disk for recording and playback, a light-pen for data input, minicomputer processing, and an electrostatic printer/plotter for hardcopy output. The method is applied to quantitative analysis of ventricular volumes, sequential ventriculography for assessment of physiologic and pharmacologic interventions, analysis of instantaneous time sequence of ventricular systolic and diastolic events, and quantitation of segmental abnormalities. The system is shown to provide the capability for computation of ventricular volumes and other measurements from operator-defined margins by greatly reducing the tedium and errors associated with manual planimetry.

Endomyocardial fibrosis in Sudan: clinical and echocardiographic features

PubMed Central

Khalil, Siddiq Ibrahim; Khalil, Suha; El Tigani, Salma; Saad, Hanan A

2017-01-01

Summary Objective: Endomyocardial fibrosis (EMF) is a rare disease and is often an underdiagnosed and forgotten cardiomyopathy. The objective of this study was to document the current frequency of EMF in Sudan by defining and selecting cases from patients attending the echocardiography laboratory. Additionally we aimed to create an EMF registry for Sudan. Methods: The study started in January 2007 and is on-going. All the patients attending our echocardiography clinics in four different hospitals in Khartoum, Sudan, were included. Transthoracic echocardiography was used as the main diagnostic and selection tool. The diagnosis of EMF was based on predefined criteria and definitions, and was further supported by additional clinical, ECG, laboratory and chest X-ray findings. Results: Out of 4 332 cases studied, 23 (0.5%) were found to have features of EMF. Females constituted 52% and the age range was 24 to 67 years. All patients presented with dyspnoea grades III–IV. Advanced heart failure with gross fluid overload was seen in 54% of cases and ascites was seen in 30%. EMF was biventricular in 53%, left ventricular in 29% and right ventricular in 18% of cases. Apical and ventricular wall fibrosis was found in all cases, followed by atrial enlargement, atrioventricular valve incompetence, ventricular cavity obliteration, restrictive flow pattern and pericardial effusion. Additional echocardiographic features are defined and discussed. Conclusion: Although a rare disease, cases of EMF can be identified in Sudan if a high index of suspicion is observed. New echocardiographic features of ventricular wall layering, endocardial fibrous shelf and endomyocardiopericarial fibrosis were identified and are discussed. PMID:28906536

Quantification of Left Ventricular Linear, Areal and Volumetric Dimensions: A Phantom and in Vivo Comparison of 2-D and Real-Time 3-D Echocardiography with Cardiovascular Magnetic Resonance.

PubMed

Polte, Christian L; Lagerstrand, Kerstin M; Gao, Sinsia A; Lamm, Carl R; Bech-Hanssen, Odd

2015-07-01

Two-dimensional echocardiography and real-time 3-D echocardiography have been reported to underestimate human left ventricular volumes significantly compared with cardiovascular magnetic resonance. We investigated the ability of 2-D echocardiography, real-time 3-D echocardiography and cardiovascular magnetic resonance to delineate dimensions of increasing complexity (diameter-area-volume) in a multimodality phantom model and in vivo, with the aim of elucidating the main cause of underestimation. All modalities were able to delineate phantom dimensions with high precision. In vivo, 2-D and real-time 3-D echocardiography underestimated short-axis end-diastolic linear and areal and all left ventricular volumetric dimensions significantly compared with cardiovascular magnetic resonance, but not short-axis end-systolic linear and areal dimensions. Underestimation increased successively from linear to volumetric left ventricular dimensions. When analyzed according to the same principles, 2-D and real-time 3-DE echocardiography provided similar left ventricular volumes. In conclusion, echocardiographic underestimation of left ventricular dimensions is due mainly to inherent technical differences in the ability to differentiate trabeculated from compact myocardium. Identical endocardial border definition criteria are needed to minimize differences between the modalities and to ensure better comparability in clinical practice. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Role of bone marrow-derived CD11c+ dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.

PubMed

Wang, Huan; Kwak, Dongmin; Fassett, John; Liu, Xiaohong; Yao, Wu; Weng, Xinyu; Xu, Xin; Xu, Yawei; Bache, Robert J; Mueller, Daniel L; Chen, Yingjie

2017-05-01

Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c + DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c + cells and the percentage of CD11c + MHCII + (major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c + DC ablation model, we found that depletion of bone marrow-derived CD11c + DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c + DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45 + cells, CD11b + cells, CD8 + T cells and activated effector CD8 + CD44 + T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c + DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.

Validation of real-time three-dimensional echocardiography for quantifying left ventricular volumes in the presence of a left ventricular aneurysm: in vitro and in vivo studies

NASA Technical Reports Server (NTRS)

Qin, J. X.; Jones, M.; Shiota, T.; Greenberg, N. L.; Tsujino, H.; Firstenberg, M. S.; Gupta, P. C.; Zetts, A. D.; Xu, Y.; Ping Sun, J.;

Effects of passive heating on central blood volume and ventricular dimensions in humans

PubMed Central

Crandall, C G; Wilson, T E; Marving, J; Vogelsang, T W; Kjaer, A; Hesse, B; Secher, N H

2008-01-01

Mixed findings regarding the effects of whole-body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non-heat stressed) subjects participated in this protocol. Changes in regional blood volume during heat stress and time control were estimated using technetium-99m labelled autologous red blood cells and gamma camera imaging. Whole-body heating increased internal temperature (≥ 1.0°C), cutaneous vascular conductance (approximately fivefold), and heart rate (52 ± 2 to 93 ± 4 beats min−1), while reducing central venous pressure (5.5 ± 07 to 0.2 ± 0.6 mmHg) accompanied by minor decreases in mean arterial pressure (all P < 0.05). The heat stress reduced the blood volume of the heart (18 ± 2%), heart plus central vasculature (17 ± 2%), thorax (14 ± 2%), inferior vena cava (23 ± 2%) and liver (23 ± 2%) (all P≤ 0.005 relative to time control subjects). Radionuclide multiple-gated acquisition assessment revealed that heat stress did not significantly change left ventricular end-diastolic volume, while ventricular end-systolic volume was reduced by 24 ± 6% of pre-heat stress levels (P < 0.001 relative to time control subjects). Thus, heat stress increased left ventricular ejection fraction from 60 ± 1% to 68 ± 2% (P= 0.02). We conclude that heat stress shifts blood volume from thoracic and splanchnic regions presumably to aid in heat dissipation, while simultaneously increasing heart rate and ejection fraction. PMID:17962331

Dependence of Intramyocardial Pressure and Coronary Flow on Ventricular Loading and Contractility: A Model Study

PubMed Central

Borsje, Petra; Arts, Theo; van De Vosse, Frans N.

2006-01-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity. PMID:17048105

IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload

PubMed Central

Sbroggiò, Mauro; Carnevale, Daniela; Bertero, Alessandro; Cifelli, Giuseppe; De Blasio, Emanuele; Mascio, Giada; Hirsch, Emilio; Bahou, Wadie F.; Turco, Emilia; Silengo, Lorenzo; Brancaccio, Mara; Lembo, Giuseppe; Tarone, Guido

2011-01-01

Aims The Raf-MEK1/2-ERK1/2 (ERK1/2—extracellular signal-regulated kinases 1/2) signalling cascade is crucial in triggering cardiac responses to different stress stimuli. Scaffold proteins are key elements in coordinating signalling molecules for their appropriate spatiotemporal activation. Here, we investigated the role of IQ motif-containing GTPase-activating protein 1 (IQGAP1), a scaffold for the ERK1/2 cascade, in heart function and remodelling in response to pressure overload. Methods and results IQGAP1-null mice have unaltered basal heart function. When subjected to pressure overload, IQGAP1-null mice initially develop a compensatory hypertrophy indistinguishable from that of wild-type (WT) mice. However, upon a prolonged stimulus, the hypertrophic response develops towards a thinning of left ventricular walls, chamber dilation, and a decrease in contractility, in an accelerated fashion compared with WT mice. This unfavourable cardiac remodelling is characterized by blunted reactivation of the foetal gene programme, impaired cardiomyocyte hypertrophy, and increased cardiomyocyte apoptosis. Analysis of signalling pathways revealed two temporally distinct waves of both ERK1/2 and AKT phosphorylation peaking, respectively, at 10 min and 4 days after aortic banding in WT hearts. IQGAP1-null mice show strongly impaired phosphorylation of MEK1/2-ERK1/2 and AKT following 4 days of pressure overload, but normal activation of these kinases after 10 min. Pull-down experiments indicated that IQGAP1 is able to bind the three components of the ERK cascade, namely c-Raf, MEK1/2, and ERK1/2, as well as AKT in the heart. Conclusion These data demonstrate, for the first time, a key role for the scaffold protein IQGAP1 in integrating hypertrophy and survival signals in the heart and regulating long-term left ventricle remodelling upon pressure overload. PMID:21493702

Pulmonary hypertension in dogs with mitral regurgitation attributable to myxomatous valve disease.

PubMed

Chiavegato, David; Borgarelli, Michele; D'Agnolo, Gino; Santilli, Roberto A

2009-01-01

Pulmonary hypertension has been associated with mitral insufficiency caused by chronic degenerative valve disease in dogs. Our aim was to search for associations between left atrial to aortic root ratio, end-systolic and end-diastolic volume indices, and changes in the right ventricular to right atrial pressure gradient as estimated by the peak velocity of tricuspid regurgitation in dogs with chronic degenerative valve disease and different classes of heart failure. Dogs, for which follow-up was available were evaluated for changes in the right ventricular to right atrial systolic pressure gradient over time. Three hundred and forty-four dogs were studied; 51 in the International Small Animal Cardiac Health Council class la, 75 in class 1b, 113 in class 2, 97 in class 3a, and 8 in class 3b. The mean values for right ventricular to right atrial systolic pressure gradient, end-systolic volume index, end-diastolic volume index, and left atrial to aortic ratio were 49.2 +/- 17.1 mmHg, 149.12 +/- 60.8 and 37.7 +/- 21.6 ml/m2, and 1.9 +/- 0.5, respectively. A weak positive correlation was found between the right ventricular to right atrial systolic pressure gradient and the left atrial to aorta ratio (r = 0.242, P < 0.0001), end-diastolic volume index (r = 0.242, P < 0.0001), and end-systolic volume index (r = 0.129, P < 0.001). Follow up was available for 49 dogs. Of these, 18 had an increased, 12 a decreased, and 19 a stable right ventricular to right atrial systolic pressure gradient despite therapy. The equivalence point between the sensitivity and specificity curves of about 80% in the coincident point corresponded to a right ventricular to right atrial systolic pressure gradient of 48 mmHg. Our results suggest an association between the progressive nature of chronic degenerative mitral valve disease and pulmonary hypertension. It is of clinical interest that, with a right ventricular to right atrial systolic pressure gradient pressure gradient at or above 48 mmHg, pulmonary hypertension does not appear to improve despite therapy targeted at lowering the left atrial load.

Echocardiographic assessment and N-terminal pro-brain natriuretic peptide in hypertensives with metabolic syndrome.

PubMed

Krzesiński, Paweł; Uziebło-Życzkowska, Beata; Gielerak, Grzegorz; Stańczyk, Adam; Piotrowicz, Katarzyna; Piechota, Wiesław; Smurzyński, Paweł; Skrobowski, Andrzej

2017-01-01

N-terminal pro-brain natriuretic peptide (NT-proBNP) release is associated with left ventricular expansion and pressure overload. Elevation of serum levels of natriuretic peptides is observed in patients with impaired as well as preserved left ventricular systolic function. High NT-proBNP has been shown to be related not only to preload but also to increased afterload, especially blood pressure and arterial stiffness. The aim of the study was to evaluate the association of NT-proBNP and echocardiographic parameters in hypertensives with metabolic syndrome. The study group comprised 133 patients (99 men; mean age 45.9 ± 9.4 years) with at least a 3-month history of arterial hypertension (stages 1 and 2) and fulfilling the diagnostic criteria for metabolic syndrome. Following initial clinical assessment, which included NT-proBNP levels, they underwent two-dimensional echocardiography. Echocardiographic abnormalities were observed in 60 subjects (45.1%), including left ventricular diastolic dysfunction (LVDdf) in 41 (30.8%) and left ventricular hypertrophy (LVH) in 35 (26.3%). Higher NT-proBNP concentrations were observed in patients with LVH, especially in the presence of LVDdf. Further analysis demonstrated that NT-proBNP correlated negatively with septal E' (r = -0.38; p = 0.015) and heart rate (r = -0.42; p = 0.006) in patients with LVDdf, and positively with left ventricular end diastolic diameter (r = 0.46; p = 0.006) and left ventricular mass index (r = 0.49; p = 0.005) in subjects with LVH. However, the analysis of ROC curves revealed no NT-proBNP level of good sensitivity and specificity in diagnosing LVDdf/LVH (maximal area under the curve 0.571). Even a relatively low NT-proBNP concentration can be a useful marker of left ventricular hypertrophy and end-diastolic wall stretch. However, in the present study there was no NT-proBNP level of satisfactory predictive value to diagnose LV abnormalities.

Adenoviral beta-adrenergic receptor kinase inhibitor gene transfer improves exercise capacity, cardiac contractility, and systemic inflammation in a model of pressure overload hypertrophy.

PubMed

Gupta, Dipin; Molina, Ezequiel J; Palma, Jon; Gaughan, John P; Long, Walter; Macha, Mahender

2008-10-01

We hypothesized that intracoronary adenoviral-mediated delivery of betaARKct would improve heart failure associated pathophysiologic abnormalities related to exercise capacity, cardiac contractility, systemic inflammation and volume overload. After aortic banding, a cohort of Sprague-Dawley rats was followed by echocardiography. When an absolute decline of 25% in fractional shortening was detected, animals were randomized to intracoronary delivery of Ad.ssARKct (n=14), Ad.beta-Gal (n=13), or followed without any other further intervention (n=18). Assessment of exercise tolerance and hemodynamic profile and measurement of markers of systemic inflammation and volume overload was performed at 7, 14, and 21 days after gene delivery. Data were analyzed using ANOVA. Animals receiving Ad.ssARKct showed improved exercise tolerance compared to Ad.Gal-treated animals at 14 days (507+/-26 s vs. 408+/-19 s, P=0.01) and 21 days (526+/-55 s vs. 323+/-19 s, P<0.001) following injection. Animals receiving Ad.ssARKct demonstrated improved +dP/dtmax (mean+/-SD, 5,581+/-960 mmHg/s vs. 3,134+/-438 mmHg/s, P<0.01) and -dP/dtmax (mean+/-SD, -3,494+/-1,269 mmHg/s vs. -1,925+/-638 mmHg/s, P<0.01) compared to Ad.Gal-treated animals at 7 days. These differences were observed up to 21 days following injection. Serum levels of IL-1, IL-6, and TNF-alpha, as well as ANP were also decreased in animals receiving Ad.betaARKct. Genetic modulation of heart failure using the betaARKct gene was associated with improved exercise capacity and cardiac function as well as amelioration in heart failure-associated profiles of systemic inflammation and volume overload.

Systolic ventricular filling.

PubMed

Torrent-Guasp, Francisco; Kocica, Mladen J; Corno, Antonio; Komeda, Masashi; Cox, James; Flotats, A; Ballester-Rodes, Manel; Carreras-Costa, Francesc

2004-03-01

The evidence of the ventricular myocardial band (VMB) has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium, making it possible to understand the principles governing electrical, mechanical and energetical events within the human heart. From the earliest Erasistratus' observations, principal mechanisms responsible for the ventricular filling have still remained obscured. Contemporary experimental and clinical investigations unequivocally support the attitude that only powerful suction force, developed by the normal ventricles, would be able to produce an efficient filling of the ventricular cavities. The true origin and the precise time frame for generating such force are still controversial. Elastic recoil and muscular contraction were the most commonly mentioned, but yet, still not clearly explained mechanisms involved in the ventricular suction. Classical concepts about timing of successive mechanical events during the cardiac cycle, also do not offer understandable insight into the mechanism of the ventricular filling. The net result is the current state of insufficient knowledge of systolic and particularly diastolic function of normal and diseased heart. Here we summarize experimental evidence and theoretical backgrounds, which could be useful in understanding the phenomenon of the ventricular filling. Anatomy of the VMB, and recent proofs for its segmental electrical and mechanical activation, undoubtedly indicates that ventricular filling is the consequence of an active muscular contraction. Contraction of the ascendent segment of the VMB, with simultaneous shortening and rectifying of its fibers, produces the paradoxical increase of the ventricular volume and lengthening of its long axis. Specific spatial arrangement of the ascendent segment fibers, their interaction with adjacent descendent segment fibers, elastic elements and intra-cavitary blood volume (hemoskeleton), explain the physical principles involved in this action. This contraction occurs during the last part of classical systole and the first part of diastole. Therefore, the most important part of ventricular diastole (i.e. the rapid filling phase), in which it receives >70% of the stroke volume, belongs to the active muscular contraction of the ascendent segment. We hope that these facts will give rise to new understanding of the principal mechanisms involved in normal and abnormal diastolic heart function.

Tendinous tissue properties after short- and long-term functional overload: Differences between controls, 12 weeks and 4 years of resistance training.

PubMed

Massey, G J; Balshaw, T G; Maden-Wilkinson, T M; Folland, J P

2018-04-01

The potential for tendinous tissues to adapt to functional overload, especially after several years of exposure to heavy-resistance training, is largely unexplored. This study compared the morphological and mechanical characteristics of the patellar tendon and knee extensor tendon-aponeurosis complex between young men exposed to long-term (4 years; n = 16), short-term (12 weeks; n = 15) and no (untrained controls; n = 39) functional overload in the form of heavy-resistance training. Patellar tendon cross-sectional area, vastus lateralis aponeurosis area and quadriceps femoris volume, plus patellar tendon stiffness and Young's modulus, and tendon-aponeurosis complex stiffness, were quantified with MRI, dynamometry and ultrasonography. As expected, long-term trained had greater muscle strength and volume (+58% and +56% vs untrained, both P < .001), as well as a greater aponeurosis area (+17% vs untrained, P < .01), but tendon cross-sectional area (mean and regional) was not different between groups. Only long-term trained had reduced patellar tendon elongation/strain over the whole force/stress range, whilst both short-term and long-term overload groups had similarly greater stiffness/Young's modulus at high force/stress (short-term +25/22%, and long-term +17/23% vs untrained; all P < .05). Tendon-aponeurosis complex stiffness was not different between groups (ANOVA, P = .149). Despite large differences in muscle strength and size, years of resistance training did not induce tendon hypertrophy. Both short-term and long-term overload demonstrated similar increases in high-force mechanical and material stiffness, but reduced elongation/strain over the whole force/stress range occurred only after years of overload, indicating a force/strain specific time-course to these adaptations. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Association between central sleep apnea and left ventricular structure: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Javaheri, Sogol; Sharma, Ravi K; Bluemke, David A; Redline, Susan

2017-08-01

We assessed whether the presence of central sleep apnea is associated with adverse left ventricular structural changes. We analysed 1412 participants from the Multi-Ethnic Study of Atherosclerosis who underwent both overnight polysomnography and cardiac magnetic resonance imaging. Subjects had been recruited 10 years earlier when free of cardiovascular disease. Our main exposure is the presence of central sleep apnea as defined by central apnea-hypopnea index = 5 or the presence of Cheyne-Stokes breathing. Outcome variables were left ventricular mass/height, left ventricular ejection fraction, and left ventricular mass/volume ratio. Multivariate linear regression models adjusted for age, gender, race, waist circumference, tobacco use, hypertension, and the obstructive apnea-hypopnea index were fit for the outcomes. Of the 1412 participants, 27 (2%) individuals had central sleep apnea. After adjusting for covariates, the presence of central sleep apnea was significantly associated with elevated left ventricular mass/volume ratio (β = 0.11 ± 0.04 g mL -1 , P = 0.0071), an adverse cardiac finding signifying concentric remodelling. © 2017 European Sleep Research Society.

[Preoperative and follow-up cardiac magnetic resonance imaging of candidates for surgical ventricular restoration].

PubMed

Rodríguez Masi, M; Martín Lores, I; Bustos García de Castro, A; Cabeza Martínez, B; Maroto Castellanos, L; Gómez de Diego, J; Ferreirós Domínguez, J

2016-01-01

To assess pre and post-operative cardiac MRI (CMR) findings in patients with left endoventriculoplasty repair for ventricular aneurysm due to ischemic heart disease. Data were retrospectively gathered on 21 patients with diagnosis of ventricular aneurysm secondary to ischemic heart disease undergoing left endoventriculoplasty repair between January 2007 and March 2013. Pre and post-operative CMR was performed in 12 patients. The following data were evaluated in pre-operative and post-operative CMR studies: quantitative analysis of left ventricular ejection fraction (LVEF), left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volume index, presence of valvular disease and intracardiac thrombi. The time between surgery and post-operative CRM studies was 3-24 months. Significant differences were found in the pre and post-operative LVEF, LVEDV and LVESV data. EF showed a median increase of 10% (IQR 2-15) (p=0.003). The LVEDV showed a median decrease of 38 ml/m(2) (IQR 18-52) (p=0.006) and the LVESV showed a median decrease of 45 ml/m(2) (IQR:12-60) (p=0.008). Post-operative ventricular volume reduction was significantly higher in those patients with preoperative LVESV >110 ml/m(2) (59 ml/m(2) and 12 ml/m(2), p=0.006). In patients with ischemic heart disease that are candidates for left endoventriculoplasty, CMR is a reliable non-invasive and reproducible technique for the evaluation of the scar before the surgery and the ventricular volumes and its evolution after endoventricular surgical repair. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

PubMed

Stone, Ian S; Barnes, Neil C; James, Wai-Yee; Midwinter, Dawn; Boubertakh, Redha; Follows, Richard; John, Leonette; Petersen, Steffen E

2016-04-01

Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

A novel cardiac MR chamber volume model for mechanical dyssynchrony assessment

NASA Astrophysics Data System (ADS)

Song, Ting; Fung, Maggie; Stainsby, Jeffrey A.; Hood, Maureen N.; Ho, Vincent B.

2009-02-01

A novel cardiac chamber volume model is proposed for the assessment of left ventricular mechanical dyssynchrony. The tool is potentially useful for assessment of regional cardiac function and identification of mechanical dyssynchrony on MRI. Dyssynchrony results typically from a contraction delay between one or more individual left ventricular segments, which in turn leads to inefficient ventricular function and ultimately heart failure. Cardiac resynchronization therapy has emerged as an electrical treatment of choice for heart failure patients with dyssynchrony. Prior MRI techniques have relied on assessments of actual cardiac wall changes either using standard cine MR images or specialized pulse sequences. In this abstract, we detail a semi-automated method that evaluates dyssynchrony based on segmental volumetric analysis of the left ventricular (LV) chamber as illustrated on standard cine MR images. Twelve sectors each were chosen for the basal and mid-ventricular slices and 8 sectors were chosen for apical slices for a total of 32 sectors. For each slice (i.e. basal, mid and apical), a systolic dyssynchrony index (SDI) was measured. SDI, a parameter used for 3D echocardiographic analysis of dyssynchrony, was defined as the corrected standard deviation of the time at which minimal volume is reached in each sector. The SDI measurement of a healthy volunteer was 3.54%. In a patient with acute myocardial infarction, the SDI measurements 10.98%, 16.57% and 1.41% for basal, mid-ventricular and apical LV slices, respectively. Based on published 3D echocardiogram reference threshold values, the patient's SDI corresponds to moderate basal dysfunction, severe mid-ventricular dysfunction, and normal apical LV function, which were confirmed on echocardiography. The LV chamber segmental volume analysis model and SDI is feasible using standard cine MR data and may provide more reliable assessment of patients with dyssynchrony especially if the LV myocardium is thin or if the MR images have spatial resolution insufficient for proper resolution of wall thickness-features problematic for dyssynchrony assessment using existing MR techniques.

Echocardiographic diagnosis of left ventricular-right atrial communication (Gerbode-type defect) in an adult with chronic renal failure: a case report.

PubMed

Eroglu, Serpil; Sade, Elif; Bozbas, Huseyin; Pirat, Bahar; Yildirir, Aylin; Muderrisoglu, Haldun

2008-03-01

Left ventricular-right atrial communication, known as a Gerbode-type defect, is a rare form of ventricular septal defect. It is usually congenital, but rarely acquired. Clinical presentation is associated with the volume of the shunt. Transthoracic echocardiography is the most useful diagnostic method. We present a 63-year-old man with chronic renal failure and left ventricular-right atrial shunt.

Experimental study of quantitative assessment of left ventricular mass with contrast enhanced real-time three-dimensional echocardiography.

PubMed

Zhuang, Lei; Wang, Xin-Fang; Xie, Ming-Xing; Chen, Li-Xin; Fei, Hong-Wen; Yang, Ying; Wang, Jing; Huang, Run-Qing; Chen, Ou-Di; Wang, Liang-Yu

2004-01-01

To evaluate the feasibility and accuracy of measurement of left ventricular mass with intravenous contrast enhanced real-time three-dimensional (RT3D) echocardiography in the experimental setting. RT3D echocardiography was performed in 13 open-chest mongrel dogs before and after intravenous infusion of a perfluorocarbon contrast agent. Left ventricular myocardium volume was measured according to the apical four-plane method provided by TomTec 4D cardio-View RT1.0 software, then the left ventricular mass was calculated as the myocardial volume multiplied by the relative density of myocardium. Correlative analysis and paired t-test were performed between left ventricular mass obtained from RT3D echocardiography and the anatomic measurements. Anatomic measurement of total left ventricular mass was 55.6 +/- 9.3 g, whereas RT3D echocardiographic calculation of left ventricular mass before and after intravenous perfluorocarbon contrast agent was 57.5 +/- 11.4 and 55.5 +/- 9.3 g, respectively. A significant correlation was observed between the RT3D echocardiographic estimates of total left ventricular mass and the corresponding anatomic measurements (r = 0.95). A strong correlation was found between RT3D echocardiographic estimates of left ventricular mass with perfluorocarbon contrast and the anatomic results (r = 0.99). Analysis of intraobserver and interobserver variability showed strong indexes of agreement in the measurement of left ventricular mass with pre and post-contrast RT3D echocardiography. Measurements of left ventricular mass derived from RT3D echocardiography with and without intravenous contrast showed a significant correlation with the anatomic results. Contrast enhanced RT3D echocardiography permitted better visualization of the endocardial border, which would provide a more accurate and reliable means of determining left ventricular myocardial mass in the experimental setting.

Loss or Inhibition of uPA or MMP-9 Attenuates LV Remodeling and Dysfunction after Acute Pressure Overload in Mice

PubMed Central

Heymans, Stephane; Lupu, Florea; Terclavers, Sven; Vanwetswinkel, Bjorn; Herbert, Jean-Marc; Baker, Andrew; Collen, Desire; Carmeliet, Peter; Moons, Lieve

2005-01-01

Left ventricular (LV) hypertrophy is a natural response of the heart to increased pressure loading, but accompanying fibrosis and dilatation may result in irreversible life-threatening heart failure. Matrix metalloproteinases (MMPs) have been invoked in various cardiac diseases, however, direct genetic evidence for a role of the plasminogen activator (PA) and MMP systems in pressure overload-induced LV hypertrophy and in heart failure is lacking. Therefore, the consequences of transverse aortic banding (TAB) were analyzed in mice lacking tissue-type PA (t-PA−/−), urokinase-type PA (u-PA−/−), or gelatinase-B (MMP-9−/−), and in wild-type (WT) mice after adenoviral gene transfer of the PA-inhibitor PAI-1 or the MMP-inhibitor TIMP-1. TAB elevated LV pressure comparably in all genotypes. In WT and t-PA−/− mice, cardiomyocyte hypertrophy was associated with myocardial fibrosis, LV dilatation and dysfunction, and pump failure after 7 weeks. In contrast, in u-PA−/− mice or in WT mice after PAI-1- and TIMP-1-gene transfer, cardiomyocyte hypertrophy was moderate and only minimally associated with cardiac fibrosis and LV dilatation, resulting in better preservation of pump function. Deficiency of MMP-9 had an intermediate effect. These findings suggest that the use of u-PA- or MMP-inhibitors might preserve cardiac pump function in LV pressure overloading. PMID:15631996

Cardiac magnetic resonance analysis of right ventricular function: comparison of quantification in the short-axis and 4-chamber planes.

PubMed

Souto Bayarri, M; Masip Capdevila, L; Remuiñan Pereira, C; Suárez-Cuenca, J J; Martínez Monzonís, A; Couto Pérez, M I; Carreira Villamor, J M

2015-01-01

To compare the methods of right ventricle segmentation in the short-axis and 4-chamber planes in cardiac magnetic resonance imaging and to correlate the findings with those of the tricuspid annular plane systolic excursion (TAPSE) method in echocardiography. We used a 1.5T MRI scanner to study 26 patients with diverse cardiovascular diseases. In all MRI studies, we obtained cine-mode images from the base to the apex in both the short-axis and 4-chamber planes using steady-state free precession sequences and 6mm thick slices. In all patients, we quantified the end-diastolic volume, end-systolic volume, and the ejection fraction of the right ventricle. On the same day as the cardiac magnetic resonance imaging study, 14 patients also underwent echocardiography with TAPSE calculation of right ventricular function. No statistically significant differences were found in the volumes and function of the right ventricle calculated using the 2 segmentation methods. The correlation between the volume estimations by the two segmentation methods was excellent (r=0,95); the correlation for the ejection fraction was slightly lower (r=0,8). The correlation between the cardiac magnetic resonance imaging estimate of right ventricular ejection fraction and TAPSE was very low (r=0,2, P<.01). Both ventricular segmentation methods quantify right ventricular function adequately. The correlation with the echocardiographic method is low. Copyright © 2012 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

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

PubMed

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

2012-05-01

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

Angiotensin-converting enzyme DD genotype in patients with primary pulmonary hypertension: increased frequency and association with preserved haemodynamics.

PubMed

Abraham, William T; Raynolds, Mary V; Badesch, David B; Wynne, Kristine M; Groves, Bertron M; Roden, Robert L; Robertson, Alastair D; Lowes, Brian D; Zisman, Lawrence S; Voelkel, Norbert F; Bristow, Michael R; Perryman, M Benjamin

2003-03-01

HYPOTHESIS/INTRODUCTION: A polymorphic marker within the angiotensin- converting enzyme (ACE) gene has been associated with circulating and tissue ACE activity and with a variety of forms of cardiovascular disease. Since angiotensin II (Ang II) causes pulmonary vasoconstriction and vascular and myocardial remodelling, we postulated a role for the renin-angiotensin system and the ACE DD genotype in the pathophysiology of primary pulmonary hypertension (PPH) and in the right ventricular response to pressure overload in these patients. The incidence of the ACE DD genotype was evaluated in 60 patients with severe PPH compared with two normal control populations, a group of healthy population-based controls (n=158) and subjects found suitable for cardiac organ donation (n=79). Genomic DNA extracted from peripheral leukocytes was amplified using the polymerase chain reaction to detect polymorphic markers. Haemodynamics were determined by right heart catheterisation in a subset of the PPH patients. The frequency of the ACE DD genotype was 45% in the patients with PPH, compared with 24% in the organ donors, and 28% in population-based healthy controls (p=0.01 for chi-square test). Of the 32 PPH patients with baseline haemodynamics, 12 exhibited the ACE DD genotype and 20 were non-DD. While the mean pulmonary artery pressure and the duration of symptoms attributable to pulmonary hypertension was not different between the DD and non-DD groups, cardiac output was significantly lower (3.29+0.27 vs. 5.07+0.37 L/minute, p=0.002) and the mean right atrial pressure tended to be higher (8.85+1.29 vs. 4.92+1.27 mmHg, p=0.08) in the non-DD group. The reduction in cardiac output seen in the non-DD group was not due to a difference in heart rate, but to a significant reduction in stroke volume, consistent with a decreased contractile state. In addition, non-DD patients exhibited a significantly worse functional capacity (NYHA Class 3.14+0.12 vs. 2.40+0.28, p=0.02). 1) The ACE DD genotype is significantly increased in patients with severe PPH compared with normal controls, suggesting that certain individuals may be genetically predisposed to developing pulmonary hypertension. 2) The ACE DD genotype is associated with preserved right ventricular function in PPH patients, supporting a compensatory myocardial or inotropic role for Ang II in the pressure overloaded right ventricle.

Cardioprotection by GSK-3 inhibition: role of enhanced glycogen synthesis and attenuation of calcium overload.

PubMed

Omar, Mohamed A; Wang, Lianguo; Clanachan, Alexander S

2010-06-01

Glycogen synthase kinase-3 (GSK-3) is a multi-functional kinase that regulates signalling pathways affecting glycogen metabolism, protein synthesis, mitosis, and apoptosis. GSK-3 inhibition limits cardiac ischaemia-reperfusion (IR) injury, but mechanisms are not clearly defined. This study tested the hypothesis that acute GSK-3 inhibition stimulates glycogen synthesis, repartitions glucose away from glycolysis, reduces proton (H+) production from glucose metabolism, and attenuates intracellular Ca2+ (Ca2+(i)) overload. In isolated perfused working rat hearts subjected to global ischaemia and reperfusion, the selective GSK-3 inhibitor, SB-216763 (SB, 3 micromol/L), when added either prior to ischaemia or at the onset of reperfusion, improved recovery of left-ventricular (LV) work. SB increased glycogen synthesis during reperfusion while glycolysis and H+ production were reduced. Rates of glucose and palmitate oxidation were improved by SB. Measurement of Ca2+(i) concentration by rapid acquisition indo-1 fluorescence imaging showed that SB, when added either prior to ischaemia or at the onset of reperfusion, reduced diastolic Ca2+(i) overload during reperfusion. In aerobic hearts depleted of glycogen by substrate-free perfusion to a level similar to that measured at the onset of reperfusion, SB accelerated glycogen synthesis and reduced glycolysis and H+ production independent of changes in LV work. Our study indicates that reduction in H+ production by GSK-3 inhibition is an early and upstream event that lessens Ca2+(i) overload during ischaemia and early reperfusion independent of LV work which enhances the recovery of post-ischaemic LV function and that may ultimately contribute to previously observed reductions in cell death and infarction.

Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy

NASA Technical Reports Server (NTRS)

Bartunek, J.; Weinberg, E. O.; Tajima, M.; Rohrbach, S.; Katz, S. E.; Douglas, P. S.; Lorell, B. H.; Schneider, M. (Principal Investigator)

2000-01-01

BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

Role of Three-Dimensional Speckle Tracking Echocardiography in the Quantification of Myocardial Iron Overload in Patients with Beta-Thalassemia Major.

PubMed

Li, Shu-Juan; Hwang, Yu-Yan; Ha, Shau-Yin; Chan, Godfrey C F; Mok, Amanda S P; Wong, Sophia J; Cheung, Yiu-Fai

2016-09-01

The new three-dimensional speckle tracking echocardiography (3DSTE) may enable comprehensive quantification of global left ventricular (LV) myocardial mechanics. Twenty-four patients aged 29.3 ± 5.2 years and 22 controls were studied. 3DSTE was performed to assess LV 3D global strain, twist and torsion, ejection fraction, and systolic dyssynchrony index (SDI). The LV SDI was calculated as % of SD of times-to-peak strain of 16 segments/RR interval. The global performance index (GPI) was calculated as (global 3D strain·torsion)/SDI. Area under the receiver operating characteristic curve (AUC) was calculated to determine the capability of 3DSTE parameters to discriminate between patients with (cardiac magnetic resonance T2* <20 ms) and those without myocardial iron overload. Compared with controls, patients had significantly lower LV global 3D strain (P < 0.001), twist (P = 0.01), torsion (P = 0.04), and ejection fraction (P < 0.001) and greater SDI (P < 0.001). The GPI was lower in patients than controls (P < 0.001). T2* value correlated positively with global 3D strain (r = 0.74, P < 0.001) and GPI (r = 0.63, P = 0.001), and negatively with SDI (r = -0.44, P = 0.03). The AUCs of GPI, global 3D strain, ejection fraction, torsion, and 1/SDI were 0.94, 0.90, 0.87, 0.82, and 0.70, respectively. The GPI cutoff of 2.7°/cm had a sensitivity of 94.9% and a specificity of 88.9% of differentiating patients with from those without myocardial iron overload. The LV composite index of strain, torsion, and dyssynchrony derived from 3DSTE enables sensitive detection of myocardial iron overload in patients with thalassemia. © 2016, Wiley Periodicals, Inc.

Role of microtubules in the contractile dysfunction of hypertrophied myocardium

NASA Technical Reports Server (NTRS)

Zile, M. R.; Koide, M.; Sato, H.; Ishiguro, Y.; Conrad, C. H.; Buckley, J. M.; Morgan, J. P.; Cooper, G. 4th

1999-01-01

OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

Non invasive evaluation of cardiomechanics in patients undergoing MitrClip procedure

PubMed Central

2013-01-01

Background In the last recent years a new percutaneous procedure, the MitraClip, has been validated for the treatment of mitral regurgitation. MitraClip procedure is a promising alternative for patients unsuitable for surgery as it reduces the risk of death related to surgery ensuring a similar result. Few data are present in literature about the variation of hemodynamic parameters and ventricular coupling after Mitraclip implantation. Methods Hemodynamic data of 18 patients enrolled for MitraClip procedure were retrospectively reviewed and analyzed. Echocardiographic measurements were obtained the day before the procedure (T0) and 21 ± 3 days after the procedure (T1), including evaluation of Ejection Fraction, mitral valve regurgitation severity and mechanism, forward Stroke Volume, left atrial volume, estimated systolic pulmonary pressure, non invasive echocardiographic estimation of single beat ventricular elastance (Es(sb)), arterial elastance (Ea) measured as systolic pressure • 0.9/ Stroke Volume, ventricular arterial coupling (Ea/Es(sb) ratio). Data were expressed as median and interquartile range. Measures obtained before and after the procedure were compared using Wilcoxon non parametric test for paired samples. Results Mitraclip procedure was effective in reducing regurgitation. We observed an amelioration of echocardiographic parameters with a reduction of estimated systolic pulmonary pressure (45 to 37,5 p = 0,0002) and left atrial volume (110 to 93 p = 0,0001). Despite a few cases decreasing in ejection fraction (37 to 35 p = 0,035), the maintained ventricular arterial coupling after the procedure (P = 0,67) was associated with an increasing in forward stroke volume (60,3 to 78 p = 0,05). Conclusion MitraClip is effective in reducing mitral valve regurgitation and determines an amelioration of hemodynamic parameters with preservation of ventricular arterial coupling. PMID:23642140

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.

Impact of the right ventricular lead position on clinical outcome and on the incidence of ventricular tachyarrhythmias in patients with CRT-D.

PubMed

Kutyifa, Valentina; Bloch Thomsen, Poul Erik; Huang, David T; Rosero, Spencer; Tompkins, Christine; Jons, Christian; McNitt, Scott; Polonsky, Bronislava; Shah, Amil; Merkely, Bela; Solomon, Scott D; Moss, Arthur J; Zareba, Wojciech; Klein, Helmut U

2013-12-01

Data on the impact of right ventricular (RV) lead location on clinical outcome and ventricular tachyarrhythmias in cardiac resynchronization therapy with defibrillator (CRT-D) patients are limited. To evaluate the impact of different RV lead locations on clinical outcome in CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial. We investigated 742 of 1089 CRT-D patients (68%) with adjudicated RV lead location enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial to evaluate the impact of RV lead location on cardiac events. The primary end point was heart failure or death; secondary end points included ventricular tachycardia (VT), ventricular fibrillation (VF), or death and VT or VF alone. Eighty-six patients had the RV lead positioned at the RV septal or right ventricular outflow tract region, combined as nonapical RV group, and 656 patients had apical RV lead location. There was no difference in the primary end point in patients with nonapical RV lead location versus those with apical RV lead location (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.54-1.80; P = .983). Echocardiographic response to CRT-D was comparable across RV lead location groups (P > .05 for left ventricular end-diastolic volume, left ventricular end-systolic volume, and left atrial volume percent change). However, nonapical RV lead location was associated with significantly higher risk of VT/VF/death (HR 2.45; 95% CI 1.36-4.41; P = .003) and VT/VF alone (HR 2.52; 95% CI 1.36-4.65; P = .002), predominantly in the first year after device implantation. Results were consistent in patients with left bundle branch block. In CRT-D patients, there is no benefit of nonapical RV lead location in clinical outcome or echocardiographic response. Moreover, nonapical RV lead location is associated with an increased risk of ventricular tachyarrhythmias, particularly in the first year after device implantation. Published by Elsevier Inc.

Stroke Volume During Concomitant Apnea and Exercise: Influence of Gravity and Venous Return

NASA Astrophysics Data System (ADS)

Hoffmann, Uwe; Drager, Tobias; Steegmanns, Ansgar; Koesterer, Thomas; Linnarsson, Dag

2008-06-01

The responses of the cardiovascular system to intensive exercise (hiP) and combined stimuli by hiP and breath-hold (hiP-BH) for 20 s were examined during changing gravity (parabolic flight) and constant gravity (1g). The basic response to microgravity (μg) during low-intensity exercise was an increase in cardiac output (CO) and stroke volume (SV) as a result of augmented venous return. When onset of hiP was superimposed, the initial augmentation of CO and SV were increased further. In contrast, when BH was added, the increases of CO and SV were slowed. We propose that this was due to a transient increase of the pulmonary blood volume with the combination of μg and BH at large lung volume, creating a temporary imbalance between right ventricular input and left ventricular output. In addition, the BH- induced relative bradycardia may have contributed to a prolongation of the right-to- left indirect ventricular interdependence.

Is Fluid Overload More Important than Diabetes in Renal Progression in Late Chronic Kidney Disease?

PubMed Central

Tsai, Yi-Chun; Tsai, Jer-Chia; Chiu, Yi-Wen; Kuo, Hung-Tien; Chen, Szu-Chia; Hwang, Shang-Jyh; Chen, Tzu-Hui; Kuo, Mei-Chuan; Chen, Hung-Chun

2013-01-01

Fluid overload is one of the major presentations in patients with late stage chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and progression of diabetic nephropathy has been associated with changes in extracellular fluid volume. The aim of the study was to assess the association of fluid overload and diabetes in commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate (eGFR) less than -3 ml/min per 1.73 m2/y) in 472 patients with stages 4-5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. The study population was further classified into four groups according to the median of relative hydration status (△HS =fluid overload/extracellular water) and the presence or absence of diabetes. The median level of relative hydration status was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had commencing dialysis, and 187 (39.6%) subjects presented rapid renal function decline during a median 17.3-month follow-up. Patients with fluid overload had a significantly increased risk for commencing dialysis and renal function decline independent of the presence or absence of diabetes. No significantly increased risk for renal progression was found between diabetes and non-diabetes in late CKD without fluid overload. In conclusion, fluid overload has a higher predictive value of an elevated risk for renal progression than diabetes in late CKD. PMID:24349311

Correlations between electrocardiogram and biomarkers in acute pulmonary embolism: Analysis of ZATPOL-2 Registry.

PubMed

Kukla, Piotr; Kosior, Dariusz A; Tomaszewski, Andrzej; Ptaszyńska-Kopczyńska, Katarzyna; Widejko, Katarzyna; Długopolski, Robert; Skrzyński, Andrzej; Błaszczak, Piotr; Fijorek, Kamil; Kurzyna, Marcin

2017-07-01

Electrocardiography (ECG) is still one of the first tests performed at admission, mostly in patients (pts) with chest pain or dyspnea. The aim of this study was to assess the correlation between electrocardiographic abnormalities and cardiac biomarkers as well as echocardiographic parameter in patients with acute pulmonary embolism. We performed a retrospective analysis of 614 pts. (F/M 334/280; mean age of 67.9 ± 16.6 years) with confirmed acute pulmonary embolism (APE) who were enrolled to the ZATPOL-2 Registry between 2012 and 2014. Elevated cardiac biomarkers were observed in 358 pts (74.4%). In this group the presence of atrial fibrillation (p = .008), right axis deviation (p = .004), S 1 Q 3 T 3 sign (p < .001), RBBB (p = .006), ST segment depression in leads V 4 -V 6 (p < .001), ST segment depression in lead I (p = .01), negative T waves in leads V 1 -V 3 (p < .001), negative T waves in leads V 4 -V 6 (p = .005), negative T waves in leads II, III and aVF (p = .005), ST segment elevation in lead aVR (p = .002), ST segment elevation in lead III (p = .0038) was significantly more frequent in comparison to subjects with normal serum level of cardiac biomarkers. In multivariate regression analysis, clinical predictors of "abnormal electrocardiogram" were as follows: increased heart rate (OR 1.09, 95% CI 1.02-1.17, p = .012), elevated troponin concentration (OR 3.33, 95% CI 1.94-5.72, p = .000), and right ventricular overload (OR 2.30, 95% CI 1.17-4.53, p = .016). Electrocardiographic signs of right ventricular strain are strongly related to elevated cardiac biomarkers and echocardiographic signs of right ventricular overload. ECG may be used in preliminary risk stratification of patient with intermediate- or high-risk forms of APE. © 2017 Wiley Periodicals, Inc.

Preventive effect of sildenafil on right ventricular function in rats with monocrotaline-induced pulmonary arterial hypertension

PubMed Central

Yoshiyuki, Rieko; Tanaka, Ryo; Fukushima, Ryuji; Machida, Noboru

2016-01-01

The present study aimed to evaluate the preventive effect of sildenafil treatment on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. Fifty-four 12-week-old male Sprague–Dawley rats were injected with MCT or saline solution (MCT-injected rats: n=36; saline: n=18). Serial echocardiography and right ventricular systolic pressure (RVSP) measurements via a cardiac catheter were performed at 2, 4 and 6 weeks after the injection. After injection of MCT, rats received oral sildenafil (MCT/sildenafil group: n=18) or no treatment (MCT group: n=18) until undergoing echocardiography and cardiac catheterization. RVSP in the MCT/sildenafil group was lower than that in the MCT group at 4 (P<0.001) and 6 weeks (P<0.001). The septal curvature was improved in the MCT/sildenafil group compared with the MCT group. This finding showed that sildenafil prevented flattening of the interventricular septum because of right ventricular pressure overload. The ratio of peak trans-tricuspid early diastolic wave velocity to active filling with atrial systolic velocity showed that sildenafil improved diastolic function. Tricuspid annular plane systolic excursion and tricuspid annular systolic velocity in the MCT/sildenafil group did not show preserved myocardial contraction after administration of sildenafil. Administration of sildenafil leads to a reduction in RVSP and improvement in cardiac function in rats with PH induced by MCT. The vasodilatory action of sildenafil improves right ventricular diastolic function, but the intrinsic, positive, inotropic effect of sildenafil is minimal. PMID:26876436

Validation of gated blood-pool SPECT cardiac measurements tested using a biventricular dynamic physical phantom.

PubMed

De Bondt, Pieter; Nichols, Kenneth; Vandenberghe, Stijn; Segers, Patrick; De Winter, Olivier; Van de Wiele, Christophe; Verdonck, Pascal; Shazad, Arsalan; Shoyeb, Abu H; De Sutter, Johan

2003-06-01

We have developed a biventricular dynamic physical cardiac phantom to test gated blood-pool (GBP) SPECT image-processing algorithms. Such phantoms provide absolute values against which to assess accuracy of both right and left computed ventricular volume and ejection fraction (EF) measurements. Two silicon-rubber chambers driven by 2 piston pumps simulated crescent-shaped right ventricles wrapped partway around ellopsoid left ventricles. Twenty experiments were performed at Ghent University, for which right and left ventricular true volume and EF ranges were 65-275 mL and 55-165 mL and 7%-49% and 12%-69%, respectively. Resulting 64 x 64 simulated GBP SPECT images acquired at 16 frames per R-R interval were sent to Columbia University, where 2 observers analyzed images independently of each other, without knowledge of true values. Algorithms automatically segmented right ventricular activity volumetrically from left ventricular activity. Automated valve planes, midventricular planes, and segmentation regions were presented to observers, who accepted these choices or modified them as necessary. One observer repeated measurements >1 mo later without reference to previous determinations. Linear correlation coefficients (r) of the mean of the 3 GBP SPECT observations versus true values for right and left ventricles were 0.80 and 0.94 for EF and 0.94 and 0.95 for volumes, respectively. Correlations for right and left ventricles were 0.97 and 0.97 for EF and 0.96 and 0.89 for volumes, respectively, for interobserver agreement and 0.97 and 0.98 for EF and 0.96 and 0.90 for volumes, respectively, for intraobserver agreement. No trends were detected, though volumes and right ventricular EFs were significantly higher than true values. Overall, GBP SPECT measurements correlated strongly with true values. The phantom evaluated shows considerable promise for helping to guide algorithm developments for improved GBP SPECT accuracy.

Comparison of echocardiographic and cardiac magnetic resonance imaging measurements of functional single ventricular volumes, mass, and ejection fraction (from the Pediatric Heart Network Fontan Cross-Sectional Study).

PubMed

Margossian, Renee; Schwartz, Marcy L; Prakash, Ashwin; Wruck, Lisa; Colan, Steven D; Atz, Andrew M; Bradley, Timothy J; Fogel, Mark A; Hurwitz, Lynne M; Marcus, Edward; Powell, Andrew J; Printz, Beth F; Puchalski, Michael D; Rychik, Jack; Shirali, Girish; Williams, Richard; Yoo, Shi-Joon; Geva, Tal

2009-08-01

Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement for qualitative grading of ventricular function by echocardiography was modest for left ventricular (LV) morphology (kappa = 0.42) and weak for right ventricular (RV) morphology (kappa = 0.12). For quantitative assessment, high intraclass correlation coefficients were found for echocardiographic interobserver agreement (LV 0.87 to 0.92, RV 0.82 to 0.85) of systolic and diastolic volumes, respectively. In contrast, intraclass correlation coefficients for LV and RV mass were moderate (LV 0.78, RV 0.72). The corresponding intraclass correlation coefficients by CMR were high (LV 0.96, RV 0.85). Volumes by echocardiography averaged 70% of CMR values. Interobserver reproducibility for the EF was similar for the 2 modalities. Although the absolute mean difference between modalities for the EF was small (<2%), 95% limits of agreement were wide. In conclusion, agreement between observers of qualitative FSV function by echocardiography is modest. Measurements of FSV volume by 2-dimensional echocardiography underestimate CMR measurements, but their reproducibility is high. Echocardiographic and CMR measurements of FSV EF demonstrate similar interobserver reproducibility, whereas measurements of FSV mass and LV diastolic volume are more reproducible by CMR.

Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial.

PubMed

van der Bom, Teun; Winter, Michiel M; Bouma, Berto J; Groenink, Maarten; Vliegen, Hubert W; Pieper, Petronella G; van Dijk, Arie P J; Sieswerda, Gertjan T; Roos-Hesselink, Jolien W; Zwinderman, Aeilko H; Mulder, Barbara J M

2013-01-22

The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, Vo(2)peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, -1.3% to 3.9%; P=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3-28 mL; P<0.01) and mass (8 g; 95% confidence interval, 2-14 g; P=0.01) in the placebo group than in the valsartan group. There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN52352170.

The correlation between pulsatile intracranial pressure and indices of intracranial pressure-volume reserve capacity: results from ventricular infusion testing.

PubMed

Eide, Per Kristian

2016-12-01

OBJECTIVE The objective of this study was to examine how pulsatile and static intracranial pressure (ICP) scores correlate with indices of intracranial pressure-volume reserve capacity, i.e., intracranial elastance (ICE) and intracranial compliance (ICC), as determined during ventricular infusion testing. METHODS All patients undergoing ventricular infusion testing and overnight ICP monitoring during the 6-year period from 2007 to 2012 were included in the study. Clinical data were retrieved from a quality registry, and the ventricular infusion pressure data and ICP scores were retrieved from a pressure database. The ICE and ICC (= 1/ICE) were computed during the infusion phase of the infusion test. RESULTS During the period from 2007 to 2012, 82 patients with possible treatment-dependent hydrocephalus underwent ventricular infusion testing within the department of neurosurgery. The infusion tests revealed a highly significant positive correlation between ICE and the pulsatile ICP scores mean wave amplitude (MWA) and rise-time coefficient (RTC), and the static ICP score mean ICP. The ICE was negatively associated with linear measures of ventricular size. The overnight ICP recordings revealed significantly increased MWA (> 4 mm Hg) and RTC (> 20 mm Hg/sec) values in patients with impaired ICC (< 0.5 ml/mm Hg). CONCLUSIONS In this study cohort, there was a significant positive correlation between pulsatile ICP and ICE measured during ventricular infusion testing. In patients with impaired ICC during infusion testing (ICC < 0.5 ml/mm Hg), overnight ICP recordings showed increased pulsatile ICP (MWA > 4 mm Hg, RTC > 20 mm Hg/sec), but not increased mean ICP (< 10-15 mm Hg). The present data support the assumption that pulsatile ICP (MWA and RTC) may serve as substitute markers of pressure-volume reserve capacity, i.e., ICE and ICC.

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

NASA Astrophysics Data System (ADS)

Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 ° head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 ° upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alterating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

1998-01-01

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

Three-Dimensional Echocardiography-Derived Non-Invasive Right Ventricular Pressure-Volume Analysis.

PubMed

Huang, Kuan-Chih; Lin, Lian-Yu; Hwang, Juey-Jen; Lin, Lung-Chun

2017-09-01

In patients with pulmonary hypertension, repeated evaluations of right ventricular (RV) function are still required for clinical decision making, but the invasive nature of current pressure-volume analysis makes conducting regular follow-ups in a clinical setting infeasible. We enrolled 12 patients with pulmonary arterial hypertension (PAH) and 10 with pulmonary venous hypertension (PVH) May 2016-October 2016. All patients underwent a clinically indicated right heart catheterization (RHC), from which the yielded right ventricular pressure recordings were conjugated with RV volume by 3-D echocardiography to generate a pressure-volume loop. A continuous-wave Doppler envelope of tricuspid regurgitation was transformed into a pressure gradient recording by the simplified Bernoulli equation, and then a systolic pressure gradient-volume (PG-V) diagram was generated from similar methods. The area enclosed by the pressure-volume loop was calculated to represent semi-invasive right ventricular stroke work (RVSW RHC ). The area between the PG-V diagram and x-axis was calculated to estimate non-invasive RVSW (RVSW echo ). Patients with PAH have higher RV pressure, lower pulmonary arterial wedge pressure and larger RV volume that was contributed by the dilation of RV mid-cavity minor dimension. We found no significant difference of traditional parameters between these two groups, but RVSW values were significantly higher in PAH patients. The RVSW values of these two methods were significantly correlated by the equation RVSW echo  = 0.8447 RVSW RHC  + 129.38 (R 2  = 0.9151, p < 0.001). The linearity remained satisfactory in both groups. We conclude that a PG-V diagram is a reliable method to estimate RVSW and to depict pathophysiological status. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Biplane roentgen videometric system for dynamic, 60/sec, studies of the shape and size of circulatory structures, particularly the left ventricle.

NASA Technical Reports Server (NTRS)

Ritman, E. L.; Sturm, R. E.; Wood, E. H.

1973-01-01

An operator interactive video system for the measurement of roentgen angiographically outlined structures is described. Left ventricular volume and three-dimensional shapes are calculated from up to 200 pairs of diameters measured from ventriculograms at the rate of 60 pairs of biplane images per second. The accuracy and reproducibility of volumes calculated by the system were established by analysis of roentgenograms of inanimate objects of known volume and by comparison of left ventricular stroke volumes calculated by the system with the stroke volumes calculated by an indicator-dilution technique and an aortic root electromagnetic flowmeter. Computer-generated display of the large amounts of data obtained by the videometry system is described.

Risk Factors and Clinical Outcomes Associated with Perioperative Transfusion-Associated Circulatory Overload

PubMed Central

Clifford, Leanne; Jia, Qing; Subramanian, Arun; Yadav, Hemang; Schroeder, Darrell R.; Kor, Daryl J.

2016-01-01

Background Transfusion-associated circulatory overload (TACO) remains under-appreciated in the perioperative environment. We aimed to characterize risk factors for perioperative TACO and better understand its impact on patient-important outcomes. Methods In this case-control study, 163 adults undergoing non-cardiac surgery who developed perioperative TACO were matched with 726 transfused controls who did not develop respiratory complications. Univariate and multivariable logistic regression analyses were used to evaluate potential risk factors for TACO. The need for postoperative mechanical ventilation, lengths of intensive care unit (ICU) and hospital stay and mortality were compared. Results For this cohort, the mean age was 71 years and 56% were male. Multivariable analysis revealed the following independent predictors of TACO: emergency surgery, chronic kidney disease, left ventricular dysfunction, prior beta-adrenergic receptor antagonist use, isolated fresh frozen plasma transfusion (versus isolated erythrocyte transfusion), mixed product transfusion (versus isolated erythrocyte transfusion), and increasing intraoperative fluid administration. Patients who developed TACO were more likely to require postoperative mechanical ventilation (73% versus 33%; p<0.001) and experienced prolonged ICU (11.1 versus 6.5 days; p<0.001) and hospital lengths of stay (19.9 versus 9.6 days; p<0.001). Survival was significantly reduced (p<0.001) in transfusion recipients who developed TACO (1-year survival 72% versus 84%). Conclusions Perioperative TACO was associated with a protracted hospital course and increased mortality. Efforts to minimize the incidence of TACO should focus on the judicious use of intraoperative blood transfusions and non-sanguineous fluid therapies, particularly in patients with chronic kidney disease, left ventricular dysfunction, chronic beta-blocker therapy, and those requiring emergency surgery. PMID:28072601

Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

PubMed

Axelsson, B; Johansson, G; Abrahamsson, P; Gupta, A; Tydén, H; Wouters, P; Haney, M

2013-07-01

Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 μg/kg bolus plus infusion 0.5 μg/kg/min (n = 7), levosimendan 24 μg/kg plus infusion 0.2 μg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium. © 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy.

PubMed

Trembley, Michael A; Quijada, Pearl; Agullo-Pascual, Esperanza; Tylock, Kevin M; Colpan, Mert; Dirkx, Ronald A; Myers, Jason R; Mickelsen, Deanne M; de Mesy Bentley, Karen; Rothenberg, Eli; Moravec, Christine S; Alexis, Jeffrey D; Gregorio, Carol C; Dirksen, Robert T; Delmar, Mario; Small, Eric M

2018-05-01

Background -Hypertrophic cardiomyocyte (CM) growth and dysfunction accompanies various forms of heart disease. The mechanisms responsible for transcriptional changes that impact cardiac physiology and the transition to heart failure (HF) are not well understood. The intercalated disc (ID) is a specialized intercellular junction coupling CM electrical activity and force transmission, and is gaining attention as a mechanosensitive signaling hub and hotspot for causative mutations in cardiomyopathy. Methods -Transmission electron microscopy, confocal microscopy, and single-molecule localization microscopy (SMLM) were used to examine changes in ID structure and protein localization in the murine and human heart. We conducted detailed cardiac functional assessment and transcriptional profiling of mice lacking myocardin-related transcription factor-A (MRTF-A) and -B specifically in adult CMs to evaluate the role of mechanosensitive regulation of gene expression in load-induced ventricular remodeling. Results -We found that MRTFs localize to IDs in the healthy human heart and accumulate in the nucleus in heart failure (HF). Although mice lacking MRTFs in adult CMs display normal cardiac physiology at baseline, pressure overload leads to rapid HF characterized by sarcomere disarray, ID disintegration, chamber dilation and wall thinning, cardiac functional decline, and partially penetrant acute lethality. Transcriptional profiling reveals a program of actin cytoskeleton and CM adhesion genes driven by MRTFs during pressure overload. Indeed, conspicuous remodeling of gap junctions at IDs identified by SMLM may partially stem from a reduction in Mapre1 expression, which we show is a direct mechanosensitive MRTF target. Conclusions -Taken together, our study describes a novel paradigm in which MRTFs control an acute mechanosensitive signaling circuit that coordinates crosstalk between the actin and microtubule cytoskeleton and maintains ID integrity and CM homeostasis in heart disease.

Myocardial Ca2+ handling and cell-to-cell coupling, key factors in prevention of sudden cardiac death.

PubMed

Tribulova, Narcis; Seki, Shingo; Radosinska, Jana; Kaplan, Peter; Babusikova, Eva; Knezl, Vladimir; Mochizuki, Seibu

2009-12-01

Using whole-heart preparations, we tested our hypothesis that Ca(2+) handling is closely related to cell-to-cell coupling at the gap junctions and that both are critical for the development and particularly the termination of ventricular fibrillation (VF) and hence the prevention of sudden arrhythmic death. Intracellular free calcium concentration ([Ca(2+)](i)), ECG, and left ventricular pressure were continuously monitored in isolated guinea pig hearts before and during development of low K(+)-induced sustained VF and during its conversion into sinus rhythm facilitated by stobadine. We also examined myocardial ultrastructure to detect cell-to-cell coupling alterations. We demonstrated that VF occurrence was preceded by a 55.9% +/- 6.2% increase in diastolic [Ca(2+)](i), which was associated with subcellular alterations indicating Ca(2+) overload of the cardiomyocytes and disorders in coupling among the cells. Moreover, VF itself further increased [Ca(2+)](i) by 58.2% +/- 3.4% and deteriorated subcellular and cell-to-cell coupling abnormalities that were heterogeneously distributed throughout the myocardium. In contrast, termination of VF and its conversion into sinus rhythm was marked by restoration of basal [Ca(2+)](i), resulting in recovery of intercellular coupling linked with synchronous contraction. Furthermore, we have shown that hearts exhibiting lower SERCA2a (sarcoplasmic reticulum Ca(2+)-ATPase) activity and abnormal intercellular coupling (as in older guinea pigs) are more prone to develop Ca(2+) overload associated with cell-to-cell uncoupling than hearts with higher SERCA2a activity (as in young guinea pigs). Consequently, young animals are better able to terminate VF spontaneously. These findings indicate the crucial role of Ca(2+) handling in relation to cell-to-cell coupling in both the occurrence and termination of malignant arrhythmia.

Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy

PubMed Central

Ramos-Kuri, Manuel; Rapti, Kleopatra; Mehel, Hind; Zhang, Shihong; Dhandapany, Perundurai S.; Liang, Lifan; García-Carrancá, Alejandro; Bobe, Regis; Fischmeister, Rodolphe; Adnot, Serge; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.

2015-01-01

The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. PMID:26260012

Pressure overload-dependent membrane type 1-matrix metalloproteinase induction: relationship to LV remodeling and fibrosis.

PubMed

Zile, Michael R; Baicu, Catalin F; Stroud, Robert E; Van Laer, An; Arroyo, Jazmine; Mukherjee, Rupak; Jones, Jeffrey A; Spinale, Francis G

2012-04-01

Increased myocardial extracellular matrix collagen represents an important structural milestone during the development of left ventricular (LV) pressure overload (PO); however, the proteolytic pathways that contribute to this process are not fully understood. This study tested the hypothesis that membrane type 1-matrix metalloproteinase (MT1-MMP) is directly induced at the transcriptional level in vivo during PO and is related to changes in LV collagen content. PO was induced in vivo by transverse aortic constriction in transgenic mice containing the full length human MT1-MMP promoter region ligated to luciferase (MT1-MMP Prom mice). MT1-MMP promoter activation (luciferase expression), expression, and activity; collagen volume fraction (CVF); and left atrial dimension were measured at 1 (n = 8), 2 (n = 12), and 4 (n = 17) wk following PO. Non-PO mice (n = 10) served as controls. Luciferase expression increased by fivefold at 1 wk, fell at 2 wk, and increased again by ninefold at 4 wk of PO (P < 0.05). MT1-MMP expression and activity increased at 1 wk, fell at 2 wk, and increased again at 4 wk after PO. CVF increased at 1 wk, remained unchanged at 2 wk, and increased by threefold at 4 wk of PO (P < 0.05). There was a strong positive correlation between CVF and MT1-MMP activity (r = 0.80, P < 0.05). Left atrial dimension remained unchanged at 1 and 2 wk but increased by 25% at 4 wk of PO. When a mechanical load was applied in vitro to LV papillary muscles isolated from MT1-MMP Prom mice, increased load caused MT1-MMP promoter activation to increase by twofold and MT1-MMP expression to increase by fivefold (P < 0.05). These findings challenge the canonical belief that PO suppresses overall matrix proteolytic activity, but rather supports the concept that certain proteases, such as MT1-MMP, play a pivotal role in PO-induced matrix remodeling and fibrosis.

Minimally invasive estimation of ventricular dead space volume through use of Frank-Starling curves.

PubMed

Davidson, Shaun; Pretty, Chris; Pironet, Antoine; Desaive, Thomas; Janssen, Nathalie; Lambermont, Bernard; Morimont, Philippe; Chase, J Geoffrey

2017-01-01

This paper develops a means of more easily and less invasively estimating ventricular dead space volume (Vd), an important, but difficult to measure physiological parameter. Vd represents a subject and condition dependent portion of measured ventricular volume that is not actively participating in ventricular function. It is employed in models based on the time varying elastance concept, which see widespread use in haemodynamic studies, and may have direct diagnostic use. The proposed method involves linear extrapolation of a Frank-Starling curve (stroke volume vs end-diastolic volume) and its end-systolic equivalent (stroke volume vs end-systolic volume), developed across normal clinical procedures such as recruitment manoeuvres, to their point of intersection with the y-axis (where stroke volume is 0) to determine Vd. To demonstrate the broad applicability of the method, it was validated across a cohort of six sedated and anaesthetised male Pietrain pigs, encompassing a variety of cardiac states from healthy baseline behaviour to circulatory failure due to septic shock induced by endotoxin infusion. Linear extrapolation of the curves was supported by strong linear correlation coefficients of R = 0.78 and R = 0.80 average for pre- and post- endotoxin infusion respectively, as well as good agreement between the two linearly extrapolated y-intercepts (Vd) for each subject (no more than 7.8% variation). Method validity was further supported by the physiologically reasonable Vd values produced, equivalent to 44.3-53.1% and 49.3-82.6% of baseline end-systolic volume before and after endotoxin infusion respectively. This method has the potential to allow Vd to be estimated without a particularly demanding, specialised protocol in an experimental environment. Further, due to the common use of both mechanical ventilation and recruitment manoeuvres in intensive care, this method, subject to the availability of multi-beat echocardiography, has the potential to allow for estimation of Vd in a clinical environment.

Dynamic characteristic mechanism of atrial septal defect using real-time three-dimensional echocardiography and evaluation of right ventricular functions.

PubMed

Sharen, Gao-Wa; Zhang, Jun; Qin, Chuan; Lv, Qing

2017-02-01

The dynamic characteristics of the area of the atrial septal defect (ASD) were evaluated using the technique of real-time three-dimensional echocardiography (RT 3DE), the potential factors responsible for the dynamic characteristics of the area of ASD were observed, and the overall and local volume and functions of the patients with ASD were measured. RT 3DE was performed on the 27 normal controls and 28 patients with ASD. Based on the three-dimensional data workstations, the area of ASD was measured at P wave vertex, R wave vertex, T wave starting point, and T wave terminal point and in the T-P section. The right atrial volume in the same time phase of the cardiac cycle and the motion displacement distance of the tricuspid annulus in the corresponding period were measured. The measured value of the area of ASD was analyzed. The changes in the right atrial volume and the motion displacement distance of the tricuspid annulus in the normal control group and the ASD group were compared. The right ventricular ejection fractions in the normal control group and the ASD group were compared using the RT 3DE long-axis eight-plane (LA 8-plane) method. Real-time three-dimensional volume imaging was performed in the normal control group and ASD group (n=30). The right ventricular inflow tract, outflow tract, cardiac apex muscular trabecula dilatation, end-systolic volume, overall dilatation, end-systolic volume, and appropriate local and overall ejection fractions in both two groups were measured with the four-dimensional right ventricular quantitative analysis method (4D RVQ) and compared. The overall right ventricular volume and the ejection fraction measured by the LA 8-plane method and 4D RVQ were subjected to a related analysis. Dynamic changes occurred to the area of ASD in the cardiac cycle. The rules for dynamic changes in the area of ASD and the rules for changes in the right atrial volume in the cardiac cycle were consistent. The maximum value of the changes in the right atrial volume occurred in the end-systolic period when the peak of the curve appeared. The minimum value of the changes occurred in the end-systolic period and was located at the lowest point of the volume variation curve. The area variation curve for ASD and the motion variation curve for the tricuspid annulus in the cardiac cycle were the same. The displacement of the tricuspid annulus exhibited directionality. The measured values of the area of ASD at P wave vertex, R wave vertex, T wave starting point, T wave terminal point and in the T-P section were properly correlated with the right atrial volume (P<0.001). The area of ASD and the motion displacement distance of the tricuspid annulus were negatively correlated (P<0.05). The right atrial volumes in the ASD group in the cardiac cycle in various time phases increased significantly as compared with those in the normal control group (P=0.0001). The motion displacement distance of the tricuspid annulus decreased significantly in the ASD group as compared with that in the normal control group (P=0.043). The right ventricular ejection fraction in the ASD group was lower than that in the normal control group (P=0.032). The ejection fraction of the cardiac apex trabecula of the ASD patients was significantly lower than the ejection fractions of the right ventricular outflow tract and inflow tract and overall ejection fraction. The difference was statistically significant (P=0.005). The right ventricular local and overall dilatation and end-systolic volumes in the ASD group increased significantly as compared with those in the normal control group (P=0.031). The aRVEF and the overall ejection fraction decreased in the ASD group as compared with those in the normal control group (P=0.0005). The dynamic changes in the area of ASD and the motion curves for the right atrial volume and tricuspid annulus have the same dynamic characteristics. RT 3DE can be used to accurately evaluate the local and overall volume and functions of the right ventricle. The local and overall volume loads of the right ventricle in the ASD patients increase significantly as compared with those of the normal people. The right ventricular cardiac apex and the overall systolic function decrease.

Associates of an elevated natriuretic peptide level in stable heart failure patients: implications for targeted management.

PubMed

Jan, Aftab; Dawkins, Ian; Murphy, Niamh; Collier, Patrick; Baugh, John; Ledwidge, Mark; McDonald, Kenneth; Watson, Chris J

2013-01-01

Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e') was measured. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e', creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e' and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.

Cardiac hypertrophy limits infarct expansion after myocardial infarction in mice.

PubMed

Iismaa, Siiri E; Li, Ming; Kesteven, Scott; Wu, Jianxin; Chan, Andrea Y; Holman, Sara R; Calvert, John W; Haq, Ahtesham Ul; Nicks, Amy M; Naqvi, Nawazish; Husain, Ahsan; Feneley, Michael P; Graham, Robert M

2018-04-17

We have previously demonstrated that adult transgenic C57BL/6J mice with CM-restricted overexpression of the dominant negative W v mutant protein (dn-c-kit-Tg) respond to pressure overload with robust cardiomyocyte (CM) cell cycle entry. Here, we tested if outcomes after myocardial infarction (MI) due to coronary artery ligation are improved in this transgenic model. Compared to non-transgenic littermates (NTLs), adult male dn-c-kit-Tg mice displayed CM hypertrophy and concentric left ventricular (LV) hypertrophy in the absence of an increase in workload. Stroke volume and cardiac output were preserved and LV wall stress was markedly lower than that in NTLs, leading to a more energy-efficient heart. In response to MI, infarct size in adult (16-week old) dn-c-kit-Tg hearts was similar to that of NTL after 24 h but was half that in NTL hearts 12 weeks post-MI. Cumulative CM cell cycle entry was only modestly increased in dn-c-kit-Tg hearts. However, dn-c-kit-Tg mice were more resistant to infarct expansion, adverse LV remodelling and contractile dysfunction, and suffered no early death from LV rupture, relative to NTL mice. Thus, pre-existing cardiac hypertrophy lowers wall stress in dn-c-kit-Tg hearts, limits infarct expansion and prevents death from myocardial rupture.

Middle-term results of trans-catheter creation of atrial communication in patients receiving mechanical circulatory support.

PubMed

O'Byrne, Michael L; Glatz, Andrew C; Rossano, Joseph W; Schiavo, Kellie L; Dori, Yoav; Rome, Jonathan J; Gillespie, Matthew J

2015-06-01

To describe our center's middle-term outcomes following trans-catheter creation of atrial communication (ASD) in patients on mechanical circulatory support. Trans-catheter creation of an ASD in patients on mechanical circulatory support is an adjuvant therapy to reduce left atrial pressure and associated morbidity. Data on middle term outcomes following this procedure, specifically in regards to the fate of the ASD, are limited. Retrospective observational study of consecutive children and adults undergoing trans-catheter creation of an atrial septal communication between 1/1/2006 and 5/1/2014, reviewing their baseline characteristics, procedural details, and data from follow-up. Over the study period, 37/227 (16%) subjects undergoing veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) underwent trans-catheter creation of an atrial communication. Mortality on VA-ECMO support in this subgroup was 19%, with an additional 24% transitioning to ventricular assist device. Of the 57% who survived to separation from VA-ECMO, 16/21 (76%) had residual atrial communications. 56% of these underwent closure procedures. Following trans-catheter creation of ASD, a residual ASD is present in the majority of assessable survivors and represents a potential volume overload and/or right to left shunt that may need to be addressed. © 2015 Wiley Periodicals, Inc.

Transcatheter closure of patent ductus arteriosus: past, present and future.

PubMed

Baruteau, Alban-Elouen; Hascoët, Sébastien; Baruteau, Julien; Boudjemline, Younes; Lambert, Virginie; Angel, Claude-Yves; Belli, Emre; Petit, Jérôme; Pass, Robert

2014-02-01

This review aims to describe the past history, present techniques and future directions in transcatheter treatment of patent ductus arteriosus (PDA). Transcatheter PDA closure is the standard of care in most cases and PDA closure is indicated in any patient with signs of left ventricular volume overload due to a ductus. In cases of left-to-right PDA with severe pulmonary arterial hypertension, closure may be performed under specific conditions. The management of clinically silent or very tiny PDAs remains highly controversial. Techniques have evolved and the transcatheter approach to PDA closure is now feasible and safe with current devices. Coils and the Amplatzer Duct Occluder are used most frequently for PDA closure worldwide, with a high occlusion rate and few complications. Transcatheter PDA closure in preterm or low-bodyweight infants remains a highly challenging procedure and further device and catheter design development is indicated before transcatheter closure is the treatment of choice in this delicate patient population. The evolution of transcatheter PDA closure from just 40 years ago with 18F sheaths to device delivery via a 3F sheath is remarkable and it is anticipated that further improvements will result in better safety and efficacy of transcatheter PDA closure techniques. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Sustained Improvement in Right Ventricular Chamber Dimensions 10 Years Following Xenograft Pulmonary Valve Replacement.

PubMed

Schubmehl, Heidi B; Swartz, Michael F; Atallah-Yunes, Nader; Wittlieb-Weber, Carol; Pratt, Rebecca E; Alfieris, George M

2017-01-01

The goals following pulmonary valve replacement (PVR) are to optimize right ventricular hemodynamics and minimize the need for subsequent reoperations on the right ventricular outflow tract. We hypothesized PVR using a xenograft valved conduit would result in superior freedom from reoperation with sustained improvement in right ventricular chamber dimensions. Xenograft valved conduits placed in patients aged >16 years were reviewed from 2000 to 2010 to allow for a 5-year minimum follow-up. Preoperative, one-year, and the most recent echocardiograms quantified right ventricular chamber dimensions, corresponding Z scores, and prosthetic valve function. Magnetic resonance imaging (MRI) studies compared preoperative and follow-up right ventricular volumes. A total of 100 patients underwent PVR at 24 (19-34) years. Freedom from reintervention was 100% at 10 years. At most recent follow-up, only one patient had greater than mild pulmonary insufficiency. The one-year (17.3 ± 7.2 mm Hg; P < .01) and most recent follow-up (18.6 ± 9.8 mm Hg; P < .01) Doppler-derived right ventricular outflow tract gradients remained significantly lower than preoperative measurements (36.7 ± 27.0 mm Hg). Similarly, right ventricular basal diameter, basal longitudinal diameter, and the corresponding Z scores remained lower at one year and follow-up from preoperative measurements. From 34 MRI studies, the right ventricular end-diastolic indexed volume (161.7 ± 58.5 vs 102.9 ± 38.3; P < .01) and pulmonary regurgitant fraction (38.0% ± 15.9% vs 0.8% ± 3.3%; P < .01) were significantly lower at 7.1 ± 3.4 years compared to the preoperative levels. Use of a xenograft valved conduit for PVR results in excellent freedom from reoperation with sustained improvement in right ventricular dimensions at an intermediate-term follow-up.

QRS Width as a Predictor of Right Ventricular Remodeling After Percutaneous Pulmonary Valve Implantation.

PubMed

Paech, C; Dähnert, I; Riede, F T; Wagner, R; Kister, T; Nieschke, K; Wagner, F; Gebauer, R A

2017-08-01

Recent data showed a right ventricular dyssynchrony in patients with tetralogy of Fallot (TOF). Percutaneous pulmonary valve implantation (PPVI) has become an important procedure to treat a pulmonary stenosis and/or regurgitation of the right ventricular outflow tract in these patients. Despite providing good results, there is still a considerable number of nonresponders to PPVI. The authors speculated that electrical dysfunction of the right ventricle plays an underestimated role in the outcome of patients after PPVI. This study aimed to investigate the influence of right ventricular electrical dysfunction, i.e., right bundle branch block (RBBB) on the RV remodeling after PPVI. The study included consecutive patients after correction of TOF with or without RBBB, who had received a PPVI previously at the Heart Center of the University of Leipzig, Germany during the period from 2012 to 2015. 24 patients were included. Patients without RBBB, i.e., with narrow QRS complexes pre-intervention, had significantly better RV function and had smaller right ventricular volumes. Patients with pre-interventionally QRS width below 150 ms showed a post-interventional remodeling of the right ventricle with the decreasing RV volumes (p = 0.001). The parameters of LV function and volume as well as RV ejection fraction remained unaffected by RBBB. The presented data indicate that the QRS width seems to be a valuable parameter in the prediction of right ventricular remodeling after PPVI, as it represents both electrical and mechanical functions of the right ventricle and may serve as an additional parameter for optimal timing of a PPVI.

Extracellular Fluid/Intracellular Fluid Volume Ratio as a Novel Risk Indicator for All-Cause Mortality and Cardiovascular Disease in Hemodialysis Patients

PubMed Central

Kim, Eun-Jung; Choi, Myung-Jin; Lee, Jeoung-Hwan; Oh, Ji-Eun; Seo, Jang-Won; Lee, Young-Ki; Yoon, Jong-Woo; Kim, Hyung-Jik; Noh, Jung-Woo

2017-01-01

Background In hemodialysis patients, fluid overload and malnutrition are accompanied by extracellular fluid (ECF) expansion and intracellular fluid (ICF) depletion, respectively. We investigated the relationship between ECF/ICF ratio (as an integrated marker reflecting both fluid overload and malnutrition) and survival and cardiovascular disease (CVD) in the context of malnutrition-inflammation-arteriosclerosis (MIA) complex. Methods Seventy-seven patients from a single hemodialysis unit were prospectively enrolled. The ECF/ICF volume was measured by segmental multi-frequency bioimpedance analysis. MIA and volume status were measured by serum albumin, C-reactive protein (CRP), pulse wave velocity (PWV) and plasma B-type natriuretic peptide (BNP), respectively. Results The mean ECF/ICF ratio was 0.56±0.06 and the cut-off value for maximum discrimination of survival was 0.57. Compared with the low ECF/ICF group, the high ECF/ICF group (ratio≥0.57, 42%) had higher all-cause mortality, CVD, CRP, PWV, and BNP, but lower serum albumin. During the 5-year follow-up, 24 all-cause mortality and 38 CVD occurred (18 and 24, respectively, in the high ECF/ICF group versus 6 and 14 respectively in the low ECF/ICF group, P<0.001). In the adjusted Cox analysis, the ECF/ICF ratio nullifies the effects of the MIA and volume status on survival and CVD and was an independent predictor of all-cause mortality and CVD: hazard ratio (95% confidence interval); 1.12 (1.01–1.25) and 1.09 (1.01–1.18) for a 0.01 increase in the ECF/ICF ratio. The degree of malnutrition (albumin), inflammation (CRP), arteriosclerosis (PWV), and fluid overload (BNP) were correlated well with the ECF/ICF ratio. Conclusions Hemodialysis patients with high ECF/ICF ratio are not only fluid overloaded, but malnourished and have stiff artery with more inflammation. The ECF/ICF ratio is highly related to the MIA complex, and is a major risk indicator for all-cause mortality and CVD. PMID:28099511

Indication for Dialysis Initiation and Mortality in Patients With Chronic Kidney Failure: A Retrospective Cohort Study

PubMed Central

Rivara, Matthew B.; Chen, Chang Huei; Nair, Anupama; Cobb, Denise; Himmelfarb, Jonathan; Mehrotra, Rajnish

2016-01-01

Background Initiation of maintenance dialysis for patients with chronic kidney failure is a period of high risk for adverse patient outcomes. Whether indications for dialysis initiation are associated with mortality among this population is unknown. Study Design Retrospective cohort study. Setting & Participants 461 patients who initiated dialysis (hemodialysis, 437; peritoneal dialysis, 24) from January 1st, 2004 through December 31st, 2012 and were treated in facilities operated by a single dialysis organization. Follow-up for the primary outcome was through December 31st, 2013. Predictor Clinically documented primary indication for dialysis initiation, as categorized into four groups: laboratory evidence of kidney function decline (reference category), uremic symptoms, volume overload or hypertension, and other/unknown. Outcomes All-cause mortality Results Over a median follow-up of 2.4 years, 183 (40%) patients died. Crude mortality rates were 10.0 (95% CI, 6.8–14.7), 12.7 (95% CI, 10.2–15.7), 21.7 (95% CI, 16.4–28.6), and 12.2 (95% CI, 6.8–14.7) per 100 patient-years among patients initiating dialysis primarily for laboratory evidence of kidney function decline, uremic symptoms, volume overload or hypertension, and other/unknown reason, respectively. Following adjustment for demographic variables, coexisting illnesses, and estimated glomerular filtration rate, initiation of dialysis for uremic symptoms, volume overload or hypertension, or for other/unknown reasons were associated with 1.12 (95% CI, 0.72–1.77), 1.71 (95% CI, 1.03–2.84), and 1.28 (95% CI, 0.73–2.26) times higher risk, respectively, for subsequent mortality compared to initiation for laboratory evidence of kidney function decline. Limitations Possibility of residual confounding by unmeasured variables; reliance on clinical documentation to ascertain exposure Conclusions Patients initiating dialysis due to volume overload may have increased risk for mortality compared to patients initiating dialysis due to laboratory evidence of kidney function decline. Further studies are needed to identify and test interventions that might reduce this risk. PMID:27637132

Creation of dialysis vascular access with normal flow increases brain natriuretic peptide levels.

PubMed

Malík, Jan; Tuka, Vladimir; Krupickova, Zdislava; Chytilova, Eva; Holaj, Robert; Slavikova, Marcela

2009-12-01

Chronic heart failure is very common in hemodialyzed patients due to several factors such as intermittent volume overload, anemia, and hypertension. Dialysis access flow is usually considered to have a minor effect. We hypothesized that creation of dialysis access with "normal" flow would lead to elevation of B-type natriuretic peptide (BNP), which is a sensitive marker of heart failure. We included subjects with a newly created, well-functioning vascular access and normal left ventricular ejection fraction. They were examined before access creation (baseline), then again 6 weeks and 6 months after the surgery. Only subjects with access flow (Qa) < 1500 ml/min were included. Changes of BNP levels and their relation to access flow were studied. We examined 35 subjects aged 60.6 +/- 13.5 years. Qa was 789 +/- 361 and 823 +/- 313 ml/min at 6 weeks and 6 months after the surgery, respectively. Within 6 weeks after access creation, BNP rose from 217 (294) to 267 (550) ng/l (median (quartile range)) with P = 0.003. Qa was significantly related to BNP levels 6 weeks after access creation (r = 0.37, P = 0.036). Six months after access creation, there was only a trend of BNP decrease (235 (308) ng/l, P = 0.44). Creatinine, blood urea nitrogen and hemoglobin levels as well as patients' weight did not change significantly. Creation of dialysis access with "normal" flow volume leads to significant increase of BNP, which is related to the value of access flow. The increase of BNP probably mirrors worsening of clinically silent heart failure.

A composite mouse model of aplastic anemia complicated with iron overload

PubMed Central

Wu, Dijiong; Wen, Xiaowen; Liu, Wenbin; Xu, Linlong; Ye, Baodong; Zhou, Yuhong

2018-01-01

Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (P<0.05). There were marked abnormalities in iron regulation gene expression between the AA and composite model groups, as seen by the significant decrease of hepcidin expression in the liver (P<0.01) that paralleled the changes in BMP6, SMAD4, and TfR2. In summary, a composite mouse model with iron overload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits. PMID:29434729

A composite mouse model of aplastic anemia complicated with iron overload.

PubMed

Wu, Dijiong; Wen, Xiaowen; Liu, Wenbin; Xu, Linlong; Ye, Baodong; Zhou, Yuhong

2018-02-01

Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (P<0.05). There were marked abnormalities in iron regulation gene expression between the AA and composite model groups, as seen by the significant decrease of hepcidin expression in the liver (P<0.01) that paralleled the changes in BMP6, SMAD4, and TfR2. In summary, a composite mouse model with iron overload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits.

Left ventricular function assessment using a fast 3D gradient echo pulse sequence: comparison to standard multi-breath hold 2D steady state free precession imaging and accounting for papillary muscles and trabeculations.

PubMed

Sievers, Burkhard; Schrader, Sebastian; Rehwald, Wolfgang; Hunold, Peter; Barkhausen, Joerg; Erbel, Raimund

2011-06-01

Papillary muscles and trabeculae for ventricular function analysis are known to significantly contribute to accurate volume and mass measurements. Fast imaging techniques such as three-dimensional steady-state free precession (3D SSFP) are increasingly being used to speed up imaging time, but sacrifice spatial resolution. It is unknown whether 3D SSFP, despite its reduced spatial resolution, allows for exact delineation of papillary muscles and trabeculations. We therefore compared 3D SSFP ventricular function measurements to those measured from standard multi-breath hold two-dimensional steady-state free precession cine images (standard 2D SSFP). 14 healthy subjects and 14 patients with impaired left ventricularfunction underwent 1.5 Tesla cine imaging. A stack of short axis images covering the left ventricle was acquired with 2D SSFP and 3D SSFP. Left ventricular volumes, ejection fraction, and mass were determined. Analysis was performed by substracting papillary muscles and trabeculae from left ventricular volumes. In addition, reproducibility was assessed. EDV, ESV, EF, and mass were not significantly different between 2D SSFP and 3D SSFP (mean difference healthy subjects: -0.06 +/- 3.2 ml, 0.54 +/- 2.2 ml, -0.45 +/- 1.8%, and 1.13 +/- 0.8 g, respectively; patients: 1.36 +/- 2.8 ml, -0.15 3.5 ml, 0.86 +/- 2.5%, and 0.91 +/- 0.9 g, respectively; P > or = 0.095). Intra- and interobserver variability was not different for 2D SSFP (P > or = 0.64 and P > or = 0.397) and 3D SSFP (P > or = 0.53 and P > or = 0.47). Differences in volumes, EF, and mass measurements between 3D SSFP and standard 2D SSFP are very small, and not statistically significant. 3D SSFP may be used for accurate ventricular function assessment when papillary muscles and trabeculations are to be taken into account.

Fatigue 󈨛. Papers presented at the International Conference on Fatigue and Fatigue Threshold (3rd) Held in Charlottesville, Virginia on June 28-July 3, 1987. Volume 3.

DTIC Science & Technology

1987-10-15

cracks and loss of fiber-matrix bond, leadin, to nonuniform loading (tensile overload) of composite structure. Figures 13 through 15 show the micro...propagation within the matrix, and alon- the interface, leading to a nonuniform load transfer from matrix to fibers, and causing tensile overload failure...long cracks, were attributed to high cyclic strains at crack tips within grains of maximum crystallographic orientation. Ma and Laire (4) studying the

Promoting PGC-1α-driven mitochondrial biogenesis is detrimental in pressure-overloaded mouse hearts

PubMed Central

Karamanlidis, Georgios; Garcia-Menendez, Lorena; Kolwicz, Stephen C.; Lee, Chi Fung

2014-01-01

Mitochondrial dysfunction in animal models of heart failure is associated with downregulation of the peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α pathway. To test whether PGC-1α is an appropriate therapeutic target for increasing mitochondrial biogenesis and improving function in heart failure, we used a transgenic (TG) mouse model of moderate overexpression of PGC-1α (∼3-fold) in the heart. TG mice had small increases in citrate synthase activity and mitochondria size in the heart without alterations in myocardial energetics or cardiac function at baseline. In vivo dobutamine stress increased fractional shortening in wild-type mice, but this increase was attenuated in TG mice, whereas ex vivo isolated perfused TG hearts demonstrated normal functional and energetic response to high workload challenge. When subjected to pressure overload by transverse aortic constriction (TAC), TG mice displayed a significantly greater acute mortality for both male and female mice; however, long-term survival up to 8 wk was similar between the two groups. TG mice also showed a greater decrease in fractional shortening and a greater increase in left ventricular chamber dimension in response to TAC. Mitochondrial gene expression and citrate synthase activity were mildly increased in TG mice compared with wild-type mice, and this difference was also maintained after TAC. Our data suggest that a moderate level of PGC-1α overexpression in the heart compromises acute survival and does not improve cardiac function during chronic pressure overload in mice. PMID:25172896

Quantification of right ventricular volumes and function by real time three-dimensional echocardiographic longitudinal axial plane method: validation in the clinical setting.

PubMed

Endo, Yuka; Maddukuri, Prasad V; Vieira, Marcelo L C; Pandian, Natesa G; Patel, Ayan R

2006-11-01

Measurement of right ventricular (RV) volumes and right ventricular ejection fraction (RVEF) by three-dimensional echocardiographic (3DE) short-axis disc summation method has been validated in multiple studies. However, in some patients, short-axis images are of insufficient quality for accurate tracing of the RV endocardial border. This study examined the accuracy of long-axis analysis in multiple planes (longitudinal axial plane method) for assessment of RV volumes and RVEF. 3DE images were analyzed in 40 subjects with a broad range of RV function. RV end-diastolic (RVEDV) and end-systolic volumes (RVESV) and RVEF were calculated by both short-axis disc summation method and longitudinal axial plane method. Excellent correlation was obtained between the two methods for RVEDV, RVESV, and RVEF (r = 0.99, 0.99, 0.94, respectively; P < 0.0001 for all comparisons). 3DE longitudinal-axis analysis is a promising technique for the evaluation of RV function, and may provide an alternative method of assessment in patients with suboptimal short-axis images.

Effect of fluid loading on left ventricular volume and stroke volume variability in patients with end-stage renal disease: a pilot study

PubMed Central

Kanda, Hirotsugu; Hirasaki, Yuji; Iida, Takafumi; Kanao-Kanda, Megumi; Toyama, Yuki; Kunisawa, Takayuki; Iwasaki, Hiroshi

2015-01-01

Purpose The aim of this study was to investigate fluid loading-induced changes in left ventricular end-diastolic volume (LVEDV) and stroke volume variability (SVV) in patients with end-stage renal disease (ESRD) using real-time three-dimensional transesophageal echocardiography and the Vigileo-FloTrac system. Patients and methods After obtaining ethics committee approval and informed consent, 28 patients undergoing peripheral vascular procedures were studied. Fourteen patients with ESRD on hemodialysis (HD) were assigned to the HD group and 14 patients without ESRD were assigned to the control group. Institutional standardized general anesthesia was provided in both groups. SVV was measured using the Vigileo-FloTrac system. Simultaneously, a full-volume three-dimensional transesophageal echocardiography dataset was acquired to measure LVEDV, left ventricular end-systolic volume, and left ventricular ejection fraction. Measurements were obtained before and after loading 500 mL hydroxyethyl starch over 30 minutes in both groups. Results In the control group, intravenous colloid infusion was associated with a significant decrease in SVV (13.8%±2.6% to 6.5%±2.6%, P<0.001) and a significant increase in LVEDV (83.6±23.4 mL to 96.1±28.8 mL, P<0.001). While SVV significantly decreased after infusion in the HD group (16.2%±6.0% to 6.2%±2.8%, P<0.001), there was no significant change in LVEDV. Conclusion Our preliminary data suggest that fluid responsiveness can be assessed not by LVEDV but also by SVV due to underlying cardiovascular pathophysiology in patients with ESRD. PMID:26527879

[Basics of emergency ultrasound].

PubMed

Schellhaas, S; Breitkreutz, R

2012-09-05

Focused ultrasound is a key methodology of critical care medicine. By referencing few ultrasound differential diagnosis, it is possible to identifying in real-time the reason of the critical state of a patient. Therefore typical focused ultrasound protocols were developed. The well known Focused Assessment with Sonography for trauma (FAST) was incorporated into the Advanced Trauma Life Support (ATLS) for shock room. Focused echocardiographic evaluation in life support (FEEL) has been designed to be conformed with the universal Advanced Life Support (ALS) algorithm and to identify treatable conditions such as acute right ventricular pressure overload in pulmonary embolism, hypovolemia, or pericardial effusion/tamponade. Using lung ultrasound one can differentiate pulmonary edema, pleural effusion or pneumothorax.

Inhibition of Matrix Metalloproteinase Activity Prevents Increases in Myocardial Tumor Necrosis Factor-α

PubMed Central

Murray, David B.; Levick, Scott P; Brower, Gregory L.; Janicki, Joseph S.

2010-01-01

Aim TNF-α is known to cause adverse myocardial remodeling. While we have previously shown a role for cardiac mast cells in mediating myocardial TNF-α, matrix metalloproteinases (MMP) activation of TNF-α may also be contributory. We sought to determine the relative roles of MMPs and cardiac mast cells in the activation of TNF-α in the hearts of rats subjected to chronic volume overload. Methods Interventions with the broad spectrum MMP inhibitor, GM6001, or the mast cell stabilizer, nedocromil, were performed in the rat aortocaval fistula (ACF) model of volume overload. Results Myocardial TNF-α levels were significantly increased in the ACF. This increase was prevented by MMP inhibition with GM6001 (p ≤ 0.001 vs. ACF). Conversely, myocardial TNF-α levels were increased in the ACF + nedocromil treated fistula groups (p ≤ 0.001 vs. sham). The degradation of interstitial collagen volume fraction seen in the untreated ACF group was prevented in both the GM6001 and nedocromil treated hearts. Significant increases in LV myocardial ET-1 levels also occurred in the ACF group at 3 days post-fistula. Whereas administration of GM6001 significantly attenuated this increase, mast cell stabilization with nedocromil markedly exacerbated the increase, producing ET-1 levels 6.5 fold and 2 fold greater than that in the sham-operated control and ACF group, respectively. Conclusion The efficacy of the MMP inhibitor, GM6001, to prevent increased levels of myocardial TNF-α is indicative of MMP-mediated cleavage of latent extracellular membrane bound TNF-α protein as the primary source of bioactive TNF-α in the myocardium of the volume-overload heart. PMID:20403361

Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling in Infants with Single Ventricle

PubMed Central

Mital, Seema; Chung, Wendy K.; Colan, Steven D.; Sleeper, Lynn A.; Manlhiot, Cedric; Arrington, Cammon B.; Cnota, James F.; Graham, Eric M.; Mitchell, Michael E.; Goldmuntz, Elizabeth; Li, Jennifer S.; Levine, Jami C.; Lee, Teresa M.; Margossian, Renee; Hsu, Daphne T.

2011-01-01

Background We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function and response to enalapril in infants with single ventricle. Methods and Results Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with RAAS upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate (eGFR), and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high-risk), and those with <2 homozygous risk genotypes (low-risk) at two time points - before the superior-cavopulmonary-connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: 38 were high-risk, 116 were low-risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and eGFR increased after SCPC in the low-risk (p<0.05) but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline and height remained lower in the high-risk group at 14 months especially in those receiving enalapril (p<0.05). Conclusions RAAS-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. RAAS genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume unloading surgery. Follow-up is warranted to assess longterm impact. Clinical Trial Registration Clinical Trials.gov Identifier NCT00113087 PMID:21576655

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.

Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex.

PubMed

Gaser, Christian; Nenadic, Igor; Buchsbaum, Bradley R; Hazlett, Erin A; Buchsbaum, Monte S

2004-01-01

Enlargement of the lateral ventricles is among the most frequently reported macroscopic brain structural changes in schizophrenia, although variable in extent and localization. The authors investigated whether ventricular enlargement is related to regionally specific volume loss. High-resolution magnetic resonance imaging scans from 39 patients with schizophrenia were analyzed with deformation-based morphometry, a voxel-wise whole brain morphometric technique. Significant negative correlations with the ventricle-brain ratio were found for voxels in the left and right thalamus and posterior putamen and in the left superior temporal gyrus and insula. Thalamic shrinkage, especially of medial nuclei and the adjacent striatum and insular cortex, appear to be important contributors to ventricular enlargement in schizophrenia.

Effects of hormone therapy on brain structure

PubMed Central

Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay; Miller, Virginia M.

2016-01-01

Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42–56 years, within 5–36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured. Results: Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = −0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups. Conclusions: Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. Classification of evidence: This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo. PMID:27473135

Effects of hormone therapy on brain structure: A randomized controlled trial.

PubMed

Kantarci, Kejal; Tosakulwong, Nirubol; Lesnick, Timothy G; Zuk, Samantha M; Gunter, Jeffrey L; Gleason, Carey E; Wharton, Whitney; Dowling, N Maritza; Vemuri, Prashanthi; Senjem, Matthew L; Shuster, Lynne T; Bailey, Kent R; Rocca, Walter A; Jack, Clifford R; Asthana, Sanjay; Miller, Virginia M

2016-08-30

To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Participants (aged 42-56 years, within 5-36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured. Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = -0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups. Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo. © 2016 American Academy of Neurology.

Emerging hemodynamic signatures of the right heart (Third International Right Heart Failure Summit, part 2).

PubMed

Maron, Bradley A

2014-12-01

Despite the importance of preserved right ventricular structure and function with respect to outcome across the spectrum of lung, cardiac, and pulmonary vascular diseases, only recently have organized efforts developed to consider the pulmonary vascular-right ventricular apparatus as a specific unit within the larger context of cardiopulmonary pathophysiology. The Third International Right Heart Failure Summit (Boston, MA) was a multidisciplinary event dedicated to promoting a dialogue about the scientific and clinical basis of right heart disease. The current review provides a synopsis of key discussions presented during the section of the summit titled "Emerging Hemodynamic Signatures of the Right Heart." Specifically, topics emphasized in this element of the symposium included (1) the effects of pulmonary vascular dysfunction at rest or provoked by exercise on the right ventricular pressure-volume relationship, (2) the role of pressure-volume loop analysis as a method to characterize right ventricular inefficiency and predict right heart failure, and (3) the importance of a systems biology approach to identifying novel factors that contribute to pathophenotypes associated with pulmonary arterial hypertension and/or right ventricular dysfunction. Collectively, these concepts frame a forward-thinking paradigm shift in the approach to right heart disease by emphasizing factors that regulate the transition from adaptive to maladaptive right ventricular-pulmonary vascular (patho)physiology.

Three-dimensional Echocardiography of Right Ventricular Function Correlates with Severity of Pediatric Pulmonary Hypertension.

PubMed

Jone, Pei-Ni; Patel, Sonali S; Cassidy, Courtney; Ivy, David Dunbar

2016-12-01

Right ventricular function and biomarkers of B-type natriuretic peptide (BNP) and N-Terminal pro-BNP (NT pro-BNP) are used to determine the severity of right ventricular failure and outcomes from pulmonary hypertension. Real-time three-dimensional echocardiography (3DE) is a novel quantitative measure of the right ventricle and decreases the geometric assumptions from conventional two-dimensional echocardiography (2DE). We correlated right ventricular functional measures using 2DE and single-beat 3DE with biomarkers and hemodynamics to determine the severity of pediatric pulmonary hypertension. We retrospectively evaluated 35 patients (mean age 12.67 ± 5.78 years) with established pulmonary hypertension who had echocardiograms and biomarkers on the same day. Ten out of 35 patients had hemodynamic evaluation within 3 days. 2DE evaluation included tricuspid annular plane systolic excursion (TAPSE), right ventricular myocardial performance index from tissue Doppler imaging (RV TDI MPI), and right ventricular fractional area change (FAC). Three-dimensional echocardiography evaluation included right ventricular ejection fraction (EF), end-systolic volume, and end-diastolic volume. The quality of the 3DE was graded as good, fair, or poor. Pearson correlation coefficients were utilized to evaluate between biomarkers and echocardiographic parameters and between hemodynamics and echocardiography. Three-dimensional echocardiography and FAC correlated significantly with BNP and NT pro-BNP. TAPSE and RV TDI MPI did not correlate significantly with biomarkers. 3D right ventricular EF correlated significantly with hemodynamics. Two-dimensional echocardiography did not correlate with hemodynamics. Single-beat 3DE is a noninvasive, feasible tool in the quantification of right ventricular function and maybe more accurate than conventional 2DE in evaluating severity of pulmonary hypertension. © 2016 Wiley Periodicals, Inc.

Orthostatic effects on echocardiographic measures of ventricular function.

PubMed

Rowland, Thomas; Unnithan, Viswanath; Barker, Piers; Guerra, Miriam; Roche, Denise; Lindley, Martin

2012-05-01

Orthostatic-induced alterations in Doppler echocardiographic measures of ventricular function have not been well-defined. Identifying such changes may provide useful insights regarding the responses of these measures to variations in ventricular loading conditions. Standard assessment of mitral inflow velocity and tissue Doppler imaging (TDI) of left ventricular longitudinal myocardial velocities was performed on 14 young males (mean age 17.9 ± 0.7 years) in the supine position and then 5 minutes after assuming a sitting position with legs dependent. Upon sitting, average values of stroke volume and cardiac output fell by 28% and 18%, respectively, while heart rate increased from 64 ± 10 to 73 ± 12 beats/min (+14%) and calculated systemic vascular resistance rose from 12.9 ± 2.2 to 16.4 ± 3.1 units (+27%). Mitral E peak velocity declined from 87 ± 16 to 64 ± 16 cm/sec, and average TDI-E' and TDI-S both decreased (by -44% and -20%, respectively). When adjusted for orthostatic decreases in left ventricular end-diastolic volume, the mean decrease in TDI-E' was reduced to -29 (P < 0.01), but no significant decline was observed in adjusted TDI-S. Average E/E' rose with sitting by 40% (P = 0.02). These findings suggest that (a) decreases in TDI measures when assuming the upright position reflect the reduction of left ventricular size; (b) orthostatic fall in TDI-E' is also related to smaller ventricular size but, in addition, to a nonspecified reduction in ventricular relaxation; and (c) values of E/E' do not reflect alterations in ventricular preload, which occur during an orthostatic challenge. © 2012, Wiley Periodicals, Inc.

Left ventricular volume analysis as a basic tool to describe cardiac function.

PubMed

Kerkhof, Peter L M; Kuznetsova, Tatiana; Ali, Rania; Handly, Neal

2018-03-01

The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.

Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia.

PubMed

Palazzuoli, Alberto; Silverberg, Donald S; Calabrò, Anna; Spinelli, Tommaso; Quatrini, Ilaria; Campagna, Maria S; Franci, Beatrice; Nuti, Ranuccio

2009-06-01

Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of beta-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous beta-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with beta-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate.

Role of bioimpedance vectorial analysis in cardio-renal syndromes.

PubMed

Aspromonte, Nadia; Cruz, Dinna N; Ronco, Claudio; Valle, Roberto

2012-01-01

The cardio-renal syndromes (CRS) are the result of complex bidirectional organ cross-talk between the heart and kidney, with tremendous overlap of diseases such as coronary heart disease, heart failure (HF), and renal dysfunction in the same patient. Volume overload plays an important role in the pathophysiology of CRS. The appropriate treatment of overhydration, particularly in HF and in chronic kidney disease, has been associated with improved outcomes and blood pressure control. Clinical examination alone is often insufficient for accurate assessment of volume status because significant volume overload can exist even in the absence of peripheral or pulmonary edema on physical examination or radiography. Bioelectrical impedance techniques increasingly are being used in the management of patients with HF and those on chronic dialysis. These methods provide more objective estimates of volume status in such patients. Used in conjunction with standard clinical assessment and biomarkers such as the natriuretic peptides, bioimpedance analysis may be useful in guiding pharmacologic and ultrafiltration therapies and subsequently restoring such patients to a euvolemic or optivolemic state. In this article, we review the use of these techniques in CRS. Copyright © 2012 Elsevier Inc. All rights reserved.

Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation.

PubMed

Lindsay, Alistair C; Harron, Katie; Jabbour, Richard J; Kanyal, Ritesh; Snow, Thomas M; Sawhney, Paramvir; Alpendurada, Francisco; Roughton, Michael; Pennell, Dudley J; Duncan, Alison; Di Mario, Carlo; Davies, Simon W; Mohiaddin, Raad H; Moat, Neil E

2016-07-01

Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported. A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival. RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation. © 2016 American Heart Association, Inc.

Three-dimensional mapping of the lateral ventricles in autism

PubMed Central

Vidal, Christine N.; Nicolsonln, Rob; Boire, Jean-Yves; Barra, Vincent; DeVito, Timothy J.; Hayashi, Kiralee M.; Geaga, Jennifer A.; Drost, Dick J.; Williamson, Peter C.; Rajakumar, Nagalingam; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

In this study, a computational mapping technique was used to examine the three-dimensional profile of the lateral ventricles in autism. T1-weighted three-dimensional magnetic resonance images of the brain were acquired from 20 males with autism (age: 10.1 ± 3.5 years) and 22 male control subjects (age: 10.7 ± 2.5 years). The lateral ventricles were delineated manually and ventricular volumes were compared between the two groups. Ventricular traces were also converted into statistical three-dimensional maps, based on anatomical surface meshes. These maps were used to visualize regional morphological differences in the thickness of the lateral ventricles between patients and controls. Although ventricular volumes measured using traditional methods did not differ significantly between groups, statistical surface maps revealed subtle, highly localized reductions in ventricular size in patients with autism in the left frontal and occipital horns. These localized reductions in the lateral ventricles may result from exaggerated brain growth early in life. PMID:18502618

Site-specific microtubule-associated protein 4 dephosphorylation causes microtubule network densification in pressure overload cardiac hypertrophy.

PubMed

Chinnakkannu, Panneerselvam; Samanna, Venkatesababa; Cheng, Guangmao; Ablonczy, Zsolt; Baicu, Catalin F; Bethard, Jennifer R; Menick, Donald R; Kuppuswamy, Dhandapani; Cooper, George

2010-07-09

In severe pressure overload-induced cardiac hypertrophy, a dense, stabilized microtubule network forms that interferes with cardiocyte contraction and microtubule-based transport. This is associated with persistent transcriptional up-regulation of cardiac alpha- and beta-tubulin and microtubule-stabilizing microtubule-associated protein 4 (MAP4). There is also extensive microtubule decoration by MAP4, suggesting greater MAP4 affinity for microtubules. Because the major determinant of this affinity is site-specific MAP4 dephosphorylation, we characterized this in hypertrophied myocardium and then assessed the functional significance of each dephosphorylation site found by mimicking it in normal cardiocytes. We first isolated MAP4 from normal and pressure overload-hypertrophied feline myocardium; volume-overloaded myocardium, which has an equal degree and duration of hypertrophy but normal functional and cytoskeletal properties, served as a control for any nonspecific growth-related effects. After cloning cDNA-encoding feline MAP4 and obtaining its deduced amino acid sequence, we characterized by mass spectrometry any site-specific MAP4 dephosphorylation. Solely in pressure overload-hypertrophied myocardium, we identified striking MAP4 dephosphorylation at Ser-472 in the MAP4 N-terminal projection domain and at Ser-924 and Ser-1056 in the assembly-promoting region of the C-terminal microtubule-binding domain. Site-directed mutagenesis of MAP4 cDNA was then used to switch each serine to non-phosphorylatable alanine. Wild-type and mutated cDNAs were used to construct adenoviruses; microtubule network density, stability, and MAP4 decoration were assessed in normal cardiocytes following an equivalent level of MAP4 expression. The Ser-924 --> Ala MAP4 mutant produced a microtubule phenotype indistinguishable from that seen in pressure overload hypertrophy, such that Ser-924 MAP4 dephosphorylation during pressure overload hypertrophy may be central to this cytoskeletal abnormality.

Fetal development and renal function in adult rats prenatally subjected to sodium overload.

PubMed

Cardoso, Henriqueta D; Cabral, Edjair V; Vieira-Filho, Leucio D; Vieyra, Adalberto; Paixão, Ana D O

2009-10-01

The aims of this study were (1) to evaluate two factors that affect fetal development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with sodium overload and (2) to correlate possible alterations in these factors with subsequent modifications in the renal function of adult offspring. Wistar dams were maintained on 0.17 M NaCl instead of water from 20 days before mating until either the twentieth pregnancy day/parturition or weaning. Colorimetric methods were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol). Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood pressure transducer, a flow probe and inulin clearance to measure mean arterial pressure (MAP), renal blood flow and glomerular filtration rate (GFR), respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h) (150%, P < 0.05). Prenatally sodium-overloaded pups showed increased U(Prot24 h) (45%, P < 0.05) but unchanged MAP, renal hemodynamics, NN and kidney Ox. Prenatally and postnatally sodium-overloaded rats showed increased U(Prot24 h) (27%, P < 0.05) and kidney Ox (44%, P < 0.05), reduced GFR (12%, P < 0.05), increased PV (26%, P < 0.05) and unchanged MAP and NN. The TG increased in both groups of treated offspring (21%, P < 0.05), whereas Chol increased only in the postnatally sodium-overloaded group. We conclude that salt overload from the prenatal stage until weaning leads to alterations in lipid metabolism and in the renal function of the pups, which are additional to those alterations seen in rats only overloaded prenatally.

Cannabinoid receptor 2 activation restricts fibrosis and alleviates hydrocephalus after intraventricular hemorrhage.

PubMed

Tan, Qiang; Chen, Qianwei; Feng, Zhou; Shi, Xia; Tang, Jun; Tao, Yihao; Jiang, Bing; Tan, Liang; Feng, Hua; Zhu, Gang; Yang, Yunfeng; Chen, Zhi

2017-01-01

Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH). The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases. However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model. Autologous non-anticoagulative blood injection model was induced to mimic ventricular extension of hemorrhage in adult Sprague-Dawley rats. Rats were randomized to receive JWH-133(CB2 agonist), SR144528 (CB2 antagonist) or saline. The lateral ventricular volumes, fibrosis in the subarachnoid space and ventricular wall, transforming growth factor-β 1(TGF-β1) in cerebrospinal fluid and brain tissue, and animal neurological scores were measured to evaluate the effects of CB2 in hydrocephalus following IVH. CB2 agonist JWH-133 significantly decreased the lateral ventricular volumes, improved the associated neurological deficits, down-regulated TGF-β1 expression, and alleviated fibrosis in the subarachnoid space and ventricular wall after IVH. All of these effects were reversed by SR144528. In conclusion, CB2 may have anti-fibrogenic effects after IVH. CB2 agonist suppressed fibrosis of ventricular system and alleviated hydrocephalus following IVH, which is partly mediated by inhibiting TGF-β1. Copyright © 2016 Elsevier B.V. All rights reserved.

Plasma bilirubin values on admission and ventricular remodeling after a first anterior ST-segment elevation acute myocardial infarction.

PubMed

Miranda, Berta; Barrabés, José A; Figueras, Jaume; Pineda, Victor; Rodríguez-Palomares, José; Lidón, Rosa-Maria; Sambola, Antonia; Bañeras, Jordi; Otaegui, Imanol; García-Dorado, David

2016-01-01

Bilirubin may elicit cardiovascular protection and heme oxygenase-1 overexpression attenuated post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and post-infarction remodeling is unknown. In 145 patients with a first anterior ST-segment elevation acute myocardial infarction (STEMI), we assessed whether plasma bilirubin on admission predicted adverse remodeling (left ventricular end-diastolic volume [LVEDV] increase ≥20% between discharge and 6 months, estimated by magnetic resonance imaging). Patients' baseline characteristics and management were comparable among bilirubin tertiles. LVEDV increased at 6 months (P < 0.001) with respect to the initial exam, but the magnitude of this increase was similar across increasing bilirubin tertiles (10.8 [30.2], 10.1 [22.9], and 12.7 [24.3]%, P = 0.500). Median (25-75 percentile) bilirubin values in patients with and without adverse remodeling were 0.75 (0.60-0.93) and 0.73 (0.60-0.92) mg/dL (P = 0.693). Absence of final TIMI flow grade 3 (odds ratio 3.92, 95% CI 1.12-13.66) and a history of hypertension (2.04, 0.93-4.50), but not admission bilirubin, were independently associated with adverse remodeling. Bilirubin also did not predict the increase in ejection fraction at 6 months. Admission bilirubin values are not related to LVEDV or ejection fraction progression after a first anterior STEMI and do not predict adverse ventricular remodeling. Key messages Bilirubin levels are inversely related to cardiovascular disease, and overexpression of heme oxygenase-1 (the enzyme that determines bilirubin production) has prevented post-infarction ventricular remodeling in experimental animals, but the association between bilirubin levels and the progression of ventricular volumes and function in patients with acute myocardial infarction remained unexplored. In this cohort of patients with a first acute anterior ST-segment elevation myocardial infarction receiving contemporary management, bilirubin levels on admission were not predictive of the changes in left ventricular volumes or ejection fraction at 6 months measured by serial cardiac magnetic resonance imaging. The data are contrary to a significant protective effect of bilirubin against post-infarction ventricular remodeling.

Myocardial perfusion and left ventricular function indices assessed by gated myocardial perfusion SPECT in methamphetamine abusers.

PubMed

Dadpour, Bita; Dabbagh Kakhki, Vahid R; Afshari, Reza; Dorri-Giv, Masoumeh; Mohajeri, Seyed A R; Ghahremani, Somayeh

2016-12-01

Methamphetamine (MA) is associated with alterations of cardiac structure and function, although it is less known. In this study, we assessed possible abnormality in myocardial perfusion and left ventricular function using gated myocardial perfusion SPECT. Fifteen patients with MA abuse, on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) MA dependency determined by Structured Clinical Interview for DSM-IV, underwent 2-day dipyridamole stress/rest Tc-sestamibi gated myocardial perfusion SPECT. An average daily dose of MA use was 0.91±1.1 (0.2-4) g. The duration of MA use was 3.4±2.1 (1-7) years. In visual and semiquantitative analyses, all patients had normal gated myocardial perfusion SPECT, with no perfusion defects. In all gated SPECT images, there was no abnormality in left ventricular wall motion and thickening. All summed stress scores and summed rest scores were below 3. Calculated left ventricular functional indices including the end-diastolic volume, end-systolic volume, and left ventricular ejection fraction were normal. Many cardiac findings because of MA mentioned in previous reports are less likely because of significant epicardial coronary artery stenosis.

Bridges Structural Health Monitoring and Deterioration Detection - Synthesis of Knowledge and Technology

DOT National Transportation Integrated Search

2010-12-01

Bridges are continuously subjected to destructive effects of material aging, widespread corrosion of steel : reinforcing bars in concrete structures, corrosion of steel structures and components, increasing traffic : volume and overloading, or simply...

Test Methods for Telemetry Systems and Subsystems Volume 1: Test Methods for Vehicle Telemetry Systems

DTIC Science & Technology

2012-05-01

Settling Time Test .............................................................................................. 3-16 3.13 Overload Recovery Test...6-7 6.7 Inter-message Gap Time Test...6-8 6.8 Response Time Test ............................................................................................. 6-9 6.9

Current Management of Calcific Aortic Stenosis

PubMed Central

Lindman, Brian R.; Bonow, Robert O.; Otto, Catherine M.

2014-01-01

Calcific aortic stenosis (AS) is a progressive disease with no effective medical therapy that ultimately requires aortic valve replacement (AVR) for severe valve obstruction. Echocardiography is the primary diagnostic approach to define valve anatomy, measure AS severity and evaluate the left ventricular (LV) response to chronic pressure overload. In asymptomatic patients, markers of disease progression include the degree of leaflet calcification, hemodynamic severity of stenosis, adverse LV remodeling, reduced LV longitudinal strain, myocardial fibrosis and pulmonary hypertension. The onset of symptoms portends a predictably high mortality rate unless AVR is performed. In symptomatic patients, AVR improves symptoms, improves survival and, in patients with LV dysfunction, improves systolic function. Poor outcomes after AVR are associated with low-flow low-gradient AS, severe ventricular fibrosis, oxygen dependent lung disease, frailty, advanced renal dysfunction and a high comorbidity score. However, in most patients with severe symptoms, AVR is lifesaving. Bioprosthetic valves are recommended for patients over the age of 65 years. Transcatheter AVR is now available for patients with severe comorbidities, is recommended in patients who are deemed inoperable and is a reasonable alternative to surgical AVR in high risk patients. PMID:23833296

Hypovolemia induced systolic anterior motion of the mitral valve in two dogs.

PubMed

Hammes, K; Novo Matos, J; Baron Toaldo, M; Glaus, T

2016-12-01

Systolic anterior (septal) motion of the mitral valve (SAM) is a common secondary phenomenon in hypertrophic cardiomyopathy (HCM) in people and cats. In humans, it is increasingly recognized that SAM may be found in other cardiac and non-cardiac disease states. In small animal cardiology, SAM unassociated with HCM has been described in dogs with mitral valve dysplasia and right ventricular pressure overload. In this report, we describe two cases of dogs where transient SAM was caused by hypovolemia. When SAM was present both dogs showed pseudohypertrophy and tachycardia. Important factors in the genesis of SAM in this scenario are probably hypovolemia induced changes in left ventricular geometry affecting the orientation of the mitral valve apparatus combined with elevated catecholamine levels. SAM associated with increased wall thickness is not pathognomonic of HCM; this observation is of particular clinical importance when extrapolated to species where HCM is highly prevalent, e.g., cats. An echocardiographic diagnosis should always be evaluated together with full clinical assessment of history and physical examination. Copyright © 2016. Published by Elsevier B.V.

Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan.

PubMed

Brickman, Adam M; Schupf, Nicole; Manly, Jennifer J; Luchsinger, José A; Andrews, Howard; Tang, Ming X; Reitz, Christiane; Small, Scott A; Mayeux, Richard; DeCarli, Charles; Brown, Truman R

2008-08-01

Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease. To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia. The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses. Sex x race/ethnicity interactions were also considered. The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan. Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia. Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images. White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery-T2-weighted MR images. Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans. Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden. African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects. Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.

Resistance training using eccentric overload induces early adaptations in skeletal muscle size.

PubMed

Norrbrand, Lena; Fluckey, James D; Pozzo, Marco; Tesch, Per A

2008-02-01

Fifteen healthy men performed a 5-week training program comprising four sets of seven unilateral, coupled concentric-eccentric knee extensions 2-3 times weekly. While eight men were assigned to training using a weight stack (WS) machine, seven men trained using a flywheel (FW) device, which inherently provides variable resistance and allows for eccentric overload. The design of these apparatuses ensured similar knee extensor muscle use and range of motion. Before and after training, maximal isometric force (MVC) was measured in tasks non-specific to the training modes. Volume of all individual quadriceps muscles was determined by magnetic resonance imaging. Performance across the 12 exercise sessions was measured using the inherent features of the devices. Whereas MVC increased (P < 0.05) at all angles measured in FW, such a change was less consistent in WS. There was a marked increase (P < 0.05) in task-specific performance (i.e., load lifted) in WS. Average work showed a non-significant 8.7% increase in FW. Quadriceps muscle volume increased (P < 0.025) in both groups after training. Although the more than twofold greater hypertrophy evident in FW (6.2%) was not statistically greater than that shown in WS (3.0%), all four individual quadriceps muscles of FW showed increased (P < 0.025) volume whereas in WS only m. rectus femoris was increased (P < 0.025). Collectively the results of this study suggest more robust muscular adaptations following flywheel than weight stack resistance exercise supporting the idea that eccentric overload offers a potent stimuli essential to optimize the benefits of resistance exercise.

Employees' Perceptions of Email Communication, Volume and Management Strategies in an Australian University

ERIC Educational Resources Information Center

Pignata, Silvia; Lushington, Kurt; Sloan, Jeremy; Buchanan, Fiona

2015-01-01

Despite email playing a central role in university business, little is known about the strategies used by staff to manage email and the factors contributing to email overload. In a mixed method study undertaken in one Australian university comparing academic (n = 193) and professional (n = 278) staff, we found that while email volume was higher in…

Reduced left ventricular filling following blood volume extraction does not result in compensatory augmentation of cardiac mechanics.

PubMed

Lord, Rachel; MacLeod, David; George, Keith; Oxborough, David; Shave, Rob; Stembridge, Mike

2018-04-01

What is the central question of this study? A reduction in left ventricular (LV) filling, and concomitant increase in heart rate, augments LV mechanics to maintain stroke volume (SV); however, the impact of reduced LV filling in isolation on SV and LV mechanics is currently unknown. What is the main finding and its importance? An isolated decrease in LV filling did not provoke a compensatory increase in mechanics to maintain SV; in contrast, LV mechanics and SV were reduced. These data indicate that when LV filling is reduced without changes in heart rate, LV mechanics do not compensate to maintain SV. An acute non-invasive reduction in preload has been shown to augment cardiac mechanics to maintain stroke volume and cardiac output. Such interventions induce concomitant changes in heart rate, whereas blood volume extraction reduces preload without changes in heart rate. Therefore, the purpose of this study was to determine whether a preload reduction in isolation resulted in augmented stroke volume achieved via enhanced cardiac mechanics. Nine healthy volunteers (four female, age 29 ± 11 years) underwent echocardiography for the assessment of left ventricular (LV) volumes and mechanics in a supine position at baseline and end extraction after the controlled removal of 25% of total blood volume (1062 ± 342 ml). Arterial blood pressure was monitored continuously by a pressure transducer attached to an indwelling radial artery catheter. Heart rate and total peripheral resistance were unchanged from baseline to end extraction, but systolic blood pressure was reduced (from 148 to 127 mmHg). From baseline to end extraction there were significant reductions in left ventricular end-diastolic volume (from 89 to 71 ml) and stroke volume (from 56 to 37 ml); however, there was no change in LV twist, basal or apical rotation. In contrast, LV longitudinal strain (from -20 to -17%) and basal circumferential strain (from -22 to -19%) were significantly reduced from baseline to end extraction. In conclusion, a reduction in preload during blood volume extraction does not result in compensatory changes in stroke volume or cardiac mechanics. Our data suggest that LV strain is dependent on LV filling and consequent geometry, whereas LV twist could be mediated by heart rate. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance

PubMed Central

van Geuns, Robert‐Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J.G.M.

2017-01-01

Abstract Aims Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast‐enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. Methods and results We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast‐enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non‐invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Conclusions Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. PMID:29154434

Guiding automated left ventricular chamber segmentation in cardiac imaging using the concept of conserved myocardial volume.

PubMed

Garson, Christopher D; Li, Bing; Acton, Scott T; Hossack, John A

2008-06-01

The active surface technique using gradient vector flow allows semi-automated segmentation of ventricular borders. The accuracy of the algorithm depends on the optimal selection of several key parameters. We investigated the use of conservation of myocardial volume for quantitative assessment of each of these parameters using synthetic and in vivo data. We predicted that for a given set of model parameters, strong conservation of volume would correlate with accurate segmentation. The metric was most useful when applied to the gradient vector field weighting and temporal step-size parameters, but less effective in guiding an optimal choice of the active surface tension and rigidity parameters.

Clinical determinants and consequences of left ventricular hypertrophy.

PubMed

Messerli, F H

1983-09-26

The left ventricle adapts to an increased afterload such as that produced by arterial hypertension with concentric left ventricular hypertrophy. However, this adaptive process can be modified by a variety of physiologic and pathophysiologic states. Progressive aging, black race, and perhaps disorders with an increased sympathetic outflow seem to accelerate left ventricular hypertrophy. Obesity and other high cardiac output states predominantly produce dilatation of the left ventricle, and their combination with arterial hypertension results in eccentric left ventricular hypertrophy. Similarly, endurance exercise increases left ventricular volume more than wall thickness, whereas isometric exercise produces an increase in wall thickness only. The presence or absence of some physiologic and pathogenetic factors has direct implication on the assessment of what constitutes a "normal" left ventricular structure and function. Left ventricular hypertrophy has been shown to increase ventricular ectopic impulse generation and to put patients at a high risk of sudden death. Moreover, the increase in myocardial mass lowers coronary reserve and enhances cardiac oxygen requirements. Thus, the presence of left ventricular hypertrophy has to be considered as an ominous sign rather than as a benign adaptive process.

Novel experimental model of pressure overload hypertrophy in rats.

PubMed

Molina, Ezequiel J; Gupta, Dipin; Palma, Jon; Torres, Denise; Gaughan, John P; Houser, Steven; Macha, Mahender

2009-05-15

We studied a novel animal model of pressure overload hypertrophy in transition to heart failure following ascending aortic constriction. We sought to assess chronologic changes in hemodynamic parameters, echocardiographic signs of left ventricular (LV) remodeling, exercise tolerance, and profiles of systemic and local inflammation. A cohort of Sprague Dawley rats underwent aortic constriction proximal to the innominate artery and were followed by echocardiography. A group of animals were euthanized 20 wk after aortic constriction, before any detectable decline in fractional shortening (normal fractional shortening (FS) or control group; n = 6). When additional animals reached an absolute 25% decline in fractional shortening, they were randomized to be euthanized on d 0 (25% downward arrow FS group; n = 5), or d 21 (>25% downward arrow FS group; n = 6). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of systemic and local inflammatory markers was performed at each time interval. An absolute decline of 25% in FS after aortic constriction was observed between 24 and 28 wk for most animals. The transition from compensated to decompensated hypertrophy was associated with markedly decreased dP/dt(max) and dP/dt(min), increased LV end-systolic diameter and LV end-diastolic diameter, stabilization of LV free wall diameter, decreased exercise performance and up-regulation in expression of interleukin-1, interleukin-6, tumor necrosis factor-alpha, and atrial natriuretic peptide. All animals developed heart failure. This study demonstrates that proximal aortic constriction in young rats represents an excellent experimental model of pressure overload hypertrophy that may be useful for testing the efficacy of novel therapies for the treatment of heart failure.

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

PubMed

Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M

2017-10-24

Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.

Population pharmacokinetic modeling of furosemide in patients with hypertension and fluid overload conditions.

PubMed

Kodati, Devender; Yellu, Narsimhareddy

2017-06-01

Furosemide is a loop diuretic drug frequently indicated in hypertension and fluid overload conditions such as congestive heart failure and hepatic cirrhosis. The purpose of the study was to establish a population pharmacokinetic model for furosemide in Indian hypertensive and fluid overload patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of furosemide. A total of 188 furosemide plasma sample concentrations from 63 patients with hypertension or fluid overload conditions were collected in this study. The population pharmacokinetic model for furosemide was built using Phoenix NLME 1.3 software. The covariates included age, sex, body surface area, bodyweight, height and creatinine clearance (CRCL). The pharmacokinetic data of furosemide was adequately explained by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and Vd/F of furosemide in the patients were 15.054Lh -1 and 4.419L, respectively. Analysis of covariates showed that CRCL was significantly influencing the clearance of furosemide. The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of furosemide in Indian patients with hypertension and fluid overload conditions. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

The Cardiovascular Effects of Obesity on Ventricular Function and Mass in Patients after Tetralogy of Fallot Repair.

PubMed

Fogel, Mark A; Pawlowski, Thomas; Keller, Marc S; Cohen, Meryl S; Goldmuntz, Elizabeth; Diaz, Laura; Li, Christine; Whitehead, Kevin K; Harris, Matthew A

2015-08-01

To determine the cardiovascular effects of obesity on patients with tetralogy of Fallot (TOF) repair. Ventricular performance measures were compared between obese (body mass index [BMI] ≥95%), overweight (85% ≤BMI <95%), and normal weight subjects (BMI <85%) in a retrospective review of patients with TOF who underwent cardiac magnetic resonance from 2005-2010. Significance was P < .05. Of 260 consecutive patients with TOF, 32 were obese (12.3%), 48 were overweight (18.5%), and 180 were normal weight (69.2%). Biventricular mass was increased in obese compared with normal weight patients with right ventricular mass more affected than left ventricular mass. Obese patients demonstrated decreased biventricular end-diastolic volume (EDV) and stroke volume (SV) when indexed to body surface area (BSA) with an increased heart rate when compared with normal weight patients; cardiac index, ejection fraction, and pulmonary regurgitation fraction were similar. When indexed to ideal BSA, biventricular EDV and SV were similar. EDV and SV for overweight patients were nearly identical to normal weight patients with ventricular mass in between the other 2 groups. Approximately 12% of patients after TOF repair referred for cardiac magnetic resonance in a tertiary referral center are obese with increased biventricular mass. Obese patients and normal weight patients have similar cardiac indices, however, when indexed to actual BSA, obese patients demonstrate decreased EDV and SV with increased heart rate and similar cardiac indices. When indexed to ideal BSA, no differences in biventricular volumes were noted. Copyright © 2015. Published by Elsevier Inc.

WEB downloadable software for training in cardiovascular hemodynamics in the (3-D) stress echo lab

PubMed Central

2010-01-01

When a physiological (exercise) stress echo is scheduled, interest focuses on wall motion segmental contraction abnormalities to diagnose ischemic response to stress, and on left ventricular ejection fraction to assess contractile reserve. Echocardiographic evaluation of volumes (plus standard assessment of heart rate and blood pressure) is ideally suited for the quantitative and accurate calculation of a set of parameters allowing a complete characterization of cardiovascular hemodynamics (including cardiac output and systemic vascular resistance), left ventricular elastance (mirroring left ventricular contractility, theoretically independent of preload and afterload changes heavily affecting the ejection fraction), arterial elastance, ventricular arterial coupling (a central determinant of net cardiovascular performance in normal and pathological conditions), and diastolic function (through the diastolic mean filling rate). All these parameters were previously inaccessible, inaccurate or labor-intensive and now become, at least in principle, available in the stress echocardiography laboratory since all of them need an accurate estimation of left ventricular volumes and stroke volume, easily derived from 3 D echo. Aims of this paper are: 1) to propose a simple method to assess a set of parameters allowing a complete characterization of cardiovascular hemodynamics in the stress echo lab, from basic measurements to calculations 2) to propose a simple, web-based software program, to learn and training calculations as a phantom of the everyday activity in the busy stress echo lab 3) to show examples of software testing in a way that proves its value. The informatics infrastructure is available on the web, linking to http://cctrainer.ifc.cnr.it PMID:21073738

Noninvasive evaluation of global and regional left ventricular function using computed tomography and magnetic resonance imaging: a meta-analysis.

PubMed

Kaniewska, Malwina; Schuetz, Georg M; Willun, Steffen; Schlattmann, Peter; Dewey, Marc

2017-04-01

To compare the diagnostic accuracy of computed tomography (CT) in the assessment of global and regional left ventricular (LV) function with magnetic resonance imaging (MRI). MEDLINE, EMBASE and ISI Web of Science were systematically reviewed. Evaluation included: ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and left ventricular mass (LVM). Differences between modalities were analysed using limits of agreement (LoA). Publication bias was measured by Egger's regression test. Heterogeneity was evaluated using Cochran's Q test and Higgins I 2 statistic. In the presence of heterogeneity the DerSimonian-Laird method was used for estimation of heterogeneity variance. Fifty-three studies including 1,814 patients were identified. The mean difference between CT and MRI was -0.56 % (LoA, -11.6-10.5 %) for EF, 2.62 ml (-34.1-39.3 ml) for EDV and 1.61 ml (-22.4-25.7 ml) for ESV, 3.21 ml (-21.8-28.3 ml) for SV and 0.13 g (-28.2-28.4 g) for LVM. CT detected wall motion abnormalities on a per-segment basis with 90 % sensitivity and 97 % specificity. CT is accurate for assessing global LV function parameters but the limits of agreement versus MRI are moderately wide, while wall motion deficits are detected with high accuracy. • CT helps to assess patients with coronary artery disease (CAD). • MRI is the reference standard for evaluation of left ventricular function. • CT provides accurate assessment of global left ventricular function.

Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

PubMed

Dai, Shuhui; Hua, Ya; Keep, Richard F; Novakovic, Nemanja; Fei, Zhou; Xi, Guohua

2018-06-05

Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2 ⁎ -weighted and T2 ⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

Lactate response to different volume patterns of power clean.

PubMed

Date, Anand S; Simonson, Shawn R; Ransdell, Lynda B; Gao, Yong

2013-03-01

The ability to metabolize or tolerate lactate and produce power simultaneously can be an important determinant of performance. Current training practices for improving lactate use include high-intensity aerobic activities or a combination of aerobic and resistance training. Excessive aerobic training may have undesired physiological adaptations (e.g., muscle loss, change in fiber types). The role of explosive power training in lactate production and use needs further clarification. We hypothesized that high-volume explosive power movements such as Olympic lifts can increase lactate production and overload lactate clearance. Hence, the purpose of this study was to assess lactate accumulation after the completion of 3 different volume patterns of power cleans. Ten male recreational athletes (age 24.22 ± 1.39 years) volunteered. Volume patterns consisted of 3 sets × 3 repetition maximum (3RM) (low volume [LV]), 3 sets × 6 reps at 80-85% of 3RM (midvolume [MV]), and 3 sets × 9 reps at 70-75% of 3RM (high volume [HV]). Rest period was identical at 2 minutes. Blood samples were collected immediately before and after each volume pattern. The HV resulted in the greatest lactate accumulation (7.43 ± 2.94 mmol·L) vs. (5.27 ± 2.48 and 4.03 ± 1.78 mmol·L in MV and LV, respectively). Mean relative increase in lactate was the highest in HV (356.34%). The findings indicate that lactate production in power cleans is largely associated with volume, determined by number of repetitions, load, and rest interval. High-volume explosive training may impose greater metabolic demands than low-volume explosive training and may improve ability to produce power in the presence of lactate. The role of explosive power training in overloading the lactate clearance mechanism should be examined further, especially for athletes of intermittent sport.

Altitude negates the benefits of aerobic training on the vascular adaptations in rats.

PubMed

Reboul, Cyril; Tanguy, Stephane; Dauzat, Michel; Obert, Philippe

2005-06-01

This study questioned the effect of living and training at moderate altitude on aortic vasoreactivity. Considering that chronic hypoxia exposure and endurance training are able to generate opposite effects on the systemic vascular reactivity, it was hypothesized that endurance training benefits on the vascular function could be limited by chronic hypoxia. Sea-level native rats were randomly assigned to N (living in normoxia), NT (living and training 5 d.wk for 5 wk in normoxia), CH (living in hypoxia, 2800 m), and CHT (living and training 5 d.wk for 5 wk in hypoxia, 2800 m) groups. Concentration response curves to epinephrine, norepinephrine, endothelin-1, acetylcholine, and sodium nitro-prusside were assessed on aortic isolated rings. Left ventricular resting and maximal (during Tyrode's infusion) stroke volumes were evaluated by Doppler-echocardiography and used as indexes of chronic aortic volume overload. The main finding was that favorable aortic vasoreactivity adaptations consecutive to sea-level training were not observed when training was conducted at altitude. An improvement in the endothelium-dependent vasorelaxation (maximal relaxation, R(max), N = 60.4 +/- 10.0 vs NT = 91.7 +/- 3.2%; P < 0.05) and a reduced sensitivity to ET-1 were observed in NT rats. Such an enhancement in endothelium-dependent vasorelaxation was not found in CHT rats (R(max): 48.4 +/- 7.8%). Moreover, a higher sensitivity to ET-1 was reported in this group. Altitude-induced limitation in aortic blood flow and shear stress could play a major role in the explanation of these specific altitude-training adaptations. If extrapolated to the peripheral vascular bed, our results have practical significance for aerobic performance as aortic vasoreactivity adaptations after altitude training could contribute to limit blood delivery to exercising muscles.

Dissociation between cardiomyocyte function and remodeling with beta-adrenergic receptor blockade in isolated canine mitral regurgitation.

PubMed

Pat, Betty; Killingsworth, Cheryl; Denney, Thomas; Zheng, Junying; Powell, Pamela; Tillson, Michael; Dillon, A Ray; Dell'Italia, Louis J

2008-12-01

The low-pressure volume overload of isolated mitral regurgitation (MR) is associated with increased adrenergic drive, left ventricular (LV) dilatation, and loss of interstitial collagen. We tested the hypothesis that beta1-adrenergic receptor blockade (beta1-RB) would attenuate LV remodeling after 4 mo of MR in the dog. beta1-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using MRI and three-dimensional (3-D) analysis, there was a 70% increase in the LV end-diastolic (LVED) volume-to-LV mass ratio, a 23% decrease in LVED midwall circumferential curvature, and a >50% increase in LVED 3-D radius/wall thickness in MR dogs that was not attenuated by beta1-RB. However, beta1-RB caused a significant increase in LVED length from the base to apex compared with untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171+/-5 microm, P<0.05) compared with normal (156+/-3 microm) and MR (165+/-4 microm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared with normal dogs (3.73+/-0.31 vs. 5.02+/-0.26%, P<0.05) and normalized with beta1-RB (4.73+/-0.48%). In addition, stimulation with the beta-adrenergic receptor agonist isoproterenol (25 nM) increased cardiomyocyte fractional shortening by 215% (P<0.05) in beta1-RB dogs compared with normal (56%) and MR (50%) dogs. In summary, beta1-RB improved LV cardiomyocyte function and beta-adrenergic receptor responsiveness despite further cell elongation. The failure to attenuate LV remodeling associated with MR could be due to a failure to improve ultrastructural changes in extracellular matrix organization.

Clinical applications of angiocardiography

NASA Technical Reports Server (NTRS)

Dodge, H. T.; Sandler, H.

1974-01-01

Several tables are presented giving left ventricular (LV) data for normal patients and patients with heart disease of varied etiologies, pointing out the salient features. Graphs showing LV pressure-volume relationships (compliance) are presented and discussed. The method developed by Rackley et al. (1964) for determining left ventricular mass in man is described, and limitations to the method are discussed. Some clinical methods for determining LV oxygen consumption are briefly described, and the relation of various abnormalities of ventricular performance to coronary artery disease and ischemic heart disease is characterized.

The relationship between single and two-dimensional indices of left ventricular size using hemodynamic transesophageal echocardiography in trauma and burn patients.

PubMed

Younan, Duraid; Beasley, T Mark; Pigott, David C; Gibson, C Blayke; Gullett, John P; Richey, Jeffrey; Pittet, Jean-Francois; Zaky, Ahmed

2017-10-11

Conventional echocardiographic technique for assessment of volume status and cardiac contractility utilizes left ventricular end-diastolic area (LVEDA) and fractional area of change (FAC), respectively. Our goal was to find a technically reliable yet faster technique to evaluate volume status and contractility by measuring left ventricular end-diastolic diameter (LVEDD) and fractional shortening (FS) in a cohort of mechanically ventilated trauma and burn patients using hemodynamic transesophageal echocardiographic (hTEE) monitoring. Retrospective chart review performed at trauma/burn intensive care unit (TBICU). Data on 88 mechanically ventilated surgical intensive care patients cared for between July 2013 and July 2015 were reviewed. Initial measurements of LVEDA, left ventricular end-systolic area (LVESA) and FAC were collected. Post-processing left ventricular end-systolic (LVESD) and end-diastolic diameters (LVEDD) were measured and fractional shortening (FS) was calculated. Two orthogonal measurements of LV diameter were obtained in transverse (Tr) and posteroanterior (PA) orientation. There was a significant correlation between transverse and posteroanterior left ventricular diameter measurements in both systole and diastole. In systole, r = 0.92, p < 0.01 for LVESD-Tr (mean 23.47 mm, SD ± 6.77) and LVESD-PA (mean 24.84 mm, SD = 8.23). In diastole, r = 0.80, p < 0.01 for LVEDD-Tr (mean 37.60 mm, SD ± 6.45), and LVEDD-PA diameters (mean 42.24 mm, SD ± 7.97). Left ventricular area (LVEDA) also significantly correlated with left ventricular diameter LVEDD-Tr (r = 0.84, p < 0.01) and LVEDD-PA (r = 0.90, p < 0.01). Both transverse and PA measurements of fractional shortening were significantly (p < 0.0001) and similarly correlated with systolic function as measured by FAC. Bland-Altman analyses also indicated that the assessment of fractional shortening using left ventricular posteroanterior diameter measurement shows agreement with FAC. Left ventricular diameter measurements are a reliable and technically feasible alternative to left ventricular area measurements in the assessment of cardiac filling and systolic function.

Power loss and right ventricular efficiency in patients after tetralogy of Fallot repair with pulmonary insufficiency: clinical implications.

PubMed

Fogel, Mark A; Sundareswaran, Kartik S; de Zelicourt, Diane; Dasi, Lakshmi P; Pawlowski, Tom; Rome, Jack; Yoganathan, Ajit P

2012-06-01

To quantify right ventricular output power and efficiency and correlate these to ventricular function in patients with repaired tetralogy of Fallot. This might aid in determining the optimal timing for pulmonary valve replacement. We reviewed the cardiac catheterization and magnetic resonance imaging data of 13 patients with tetralogy of Fallot (age, 22 ± 17 years). Using pressure and flow measurements in the main pulmonary artery, cardiac output and regurgitation fraction, right ventricular (RV) power output, loss, and efficiency were calculated. The RV function was evaluated using cardiac magnetic resonance imaging. The RV systolic power was 1.08 ± 0.62 W, with 20.3% ± 8.6% power loss owing to 41% ± 14% pulmonary regurgitation (efficiency, 79.7% ± 8.6%; 0.84 ± 0.73 W), resulting in a net cardiac output of 4.24 ± 1.82 L/min. Power loss correlated significantly with the indexed RV end-diastolic and end-systolic volume (R = 0.78, P = .002 and R = 0.69, P = .009, respectively). The normalized RV power output had a significant negative correlation with RV end-diastolic and end-systolic volumes (both R = -0.87, P = .002 and R = -0.68, P = .023, respectively). A rapid decrease occurred in the RV power capacity with an increasing RV volume, with the curve flattening out at an indexed RV end-diastolic and end-systolic volume threshold of 139 mL/m(2) and 75 mL/m(2), respectively. Significant power loss is present in patients with repaired tetralogy of Fallot and pulmonary regurgitation. A rapid decrease in efficiency occurs with increasing RV volume, suggesting that pulmonary valve replacement should be done before the critical value of 139 mL/m(2) and 75 mL/m(2) for the RV end-diastolic and end-systolic volume, respectively, to preserve RV function. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Right ventricular beneficial effects of beta adrenergic receptor kinase inhibitor (betaARKct) gene transfer in a rat model of severe pressure overload.

PubMed

Molina, Ezequiel J; Gupta, Dipin; Palma, Jon; Gaughan, John P; Macha, Mahender

2009-06-01

Heart failure is associated with abnormalities in betaAR cascade regulation, calcium cycling, expression of inflammatory mediators and apoptosis. Adenoviral mediated gene transfer of betaARKct has beneficial indirect effects on these pathologic processes upon the left ventricular myocardium. The concomitant biochemical changes that occur in the right ventricle have not been well characterized. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After a decrease in fractional shortening of 25% from baseline, intracoronary injection of adenoviral-betaARKct (n=14) or adenoviral-beta-galactosidase (control, n=13) was performed. Rats were randomly euthanized on post-operative day 7, 14 or 21. Protein analysis including RV myocardial levels of betaARKct, betaARK1, SERCA(2a), inflammatory tissue mediators (IL-1, IL-6 and TNF-alpha), apoptotic markers (bax and bak), and MAP kinases (jnk, p38 and erk) was performed. ANOVA was employed for group comparison. Adenoviral-betaARKct treated animals showed increased expression of betaARKct and decreased levels of betaARK1 compared with controls. This treatment group also demonstrated normalization of SERCA(2a) expression and decreased levels of the inflammatory markers IL-1, IL-6 and TNF-alpha. The pro-apoptotic markers bax and bak were similarly improved. Ventricular levels of the MAP kinase jnk were increased. Differences were most significant 7 days after gene transfer, but the majority of these changes persisted at 21 days. These results suggest that attenuation of the pathologic mechanisms of beta adrenergic receptor desensitization, SERCA(2a) expression, inflammation and apoptosis, not only occur in the left ventricle but also in the right ventricular myocardium after intracoronary gene transfer of betaARKct during heart failure.

Overexpression of SARAF Ameliorates Pressure Overload-Induced Cardiac Hypertrophy Through Suppressing STIM1-Orai1 in Mice.

PubMed

Dai, Fengdan; Zhang, Yan; Wang, Qiang; Li, De; Yang, Yongjian; Ma, Shuangtao; Yang, Dachun

2018-01-01

Activation of stromal interaction molecule 1 (STIM1) and Orai1 participates in the development of cardiac hypertrophy. Store-operated Ca2+ entry-associated regulatory factor (SARAF) is an intrinsic inhibitor of STIM1-Orai1 interaction. Thus, we hypothesized that SARAF could prevent cardiac hypertrophy. Male C57BL/6 mice, aged 8 weeks, were randomly divided into sham and abdominal aortic constriction surgery groups and were infected with lentiviruses expressing SARAF and GFP (Lenti-SARAF) or GFP alone (Lenti-GFP) via intramyocardial injection. At 4 weeks after aortic constriction, left ventricular structure and function were assessed by echocardiography and hemodynamic assays. The gene and protein expressions of SARAF, STIM1, and Orai1 were measured by quantitative PCR and Western blot, respectively. Gene and protein expressions of SARAF were significantly decreased, while STIM1 and Orai1 were increased in the heart tissue compared with sham group. Overexpression of SARAF in the heart prevented the upregulation of STIM1 and Orai1, and importantly, attenuated aortic constriction-induced decrease in maximal rate of left ventricular pressure decay and increases in thickness of interventricular septum and left ventricular posterior wall, heart weight/body weight ratio, and size of cardiomyocytes. Blood pressure detected through the carotid artery and left ventricular systolic function were not affected by SARAF overexpression. In addition, overexpression of SARAF also attenuated angiotensin II-induced upregulation of STIM1 and Orai1 and hypertrophy of cultured cardiomyocytes. Overexpression of SARAF in the heart prevents cardiac hypertrophy, probably through suppressing the upregulation of STIM1/Orai1. © 2018 The Author(s). Published by S. Karger AG, Basel.

Melatonin prevents fibrosis but not hypertrophy development in the left ventricle of NG-nitro-L-arginine-methyl ester hypertensive rats.

PubMed

Paulis, Ludovit; Pechanova, Olga; Zicha, Josef; Krajcirovicova, Kristina; Barta, Andrej; Pelouch, Vaclav; Adamcova, Michaela; Simko, Fedor

2009-08-01

Melatonin was shown to reduce blood pressure, enhance nitric oxide availability and scavenge free radicals. There is, however, a shortage of data with respect to the effect of melatonin on pathological left ventricular remodelling associated with haemodynamic overload. We investigated whether melatonin was able to prevent left ventricular hypertrophy (LVH) and fibrosis associated with N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension. Four groups of male Wistar rats were investigated: control, L-NAME (50 mg/kg per day), melatonin (10 mg/kg per day) and L-NAME plus melatonin. Blood pressure was measured non-invasively each week. After 5 weeks of treatment the animals were killed and nitric oxide synthase (NOS) activity, endothelial and inducible NOS expression, the level of collagenous proteins, hydroxyproline and conjugated dienes in the left ventricle were determined. The administration of L-NAME inhibited NOS activity, increased conjugated dienes concentration, elevated blood pressure and induced LVH and fibrosis (indicated by increased collagenous proteins and hydroxyproline levels). The addition of melatonin to L-NAME treatment failed to prevent the attenuation of NOS activity and the development of LVH and prevented hypertension only partly. The administration of melatonin, however, completely prevented the increase in conjugated dienes concentration and the development of left ventricular fibrosis. NOS expression was not different among experimental groups. Melatonin prevented the development of left ventricular fibrosis and the increase in oxidative load in rats with L-NAME-induced hypertension. The antifibrotic effect of melatonin seems to be independent of its effects on NOS activity and might be linked to its antioxidant properties.

Tricuspid regurgitation after successful mitral valve surgery

PubMed Central

Katsi, Vasiliki; Raftopoulos, Leonidas; Aggeli, Constantina; Vlasseros, Ioannis; Felekos, Ioannis; Tousoulis, Dimitrios; Stefanadis, Christodoulos; Kallikazaros, Ioannis

2012-01-01

The tricuspid valve (TV) is inseparably connected with the mitral valve (MV) in terms of function. Any pathophysiological condition concerning the MV is potentially a threat for the normal function of the TV as well. One of the most challenging cases is functional tricuspid regurgitation (TR) after surgical MV correction. In the past, TR was considered to progressively revert with time after left-sided valve restoration. Nevertheless, more recent studies showed that TR could develop and evolve postoperatively over time, as well as being closely associated with a poorer prognosis in terms of morbidity and mortality. Pressure and volume overload are usually the underlying pathophysiological mechanisms; structural alterations, like tricuspid annulus dilatation, increased leaflet tethering and right ventricular remodelling are almost always present when regurgitation develops. The most important risk factors associated with a higher probability of late TR development involve the elderly, female gender, larger left atrial size, atrial fibrillation, right chamber dilatation, higher pulmonary artery systolic pressures, longer times from the onset of MV disease to surgery, history of rheumatic heart disease, ischaemic heart disease and prosthetic valve malfunction. The time of TR manifestation can be up to 10 years or more after an MV surgery. Echocardiography, including the novel 3D Echo techniques, is crucial in the early diagnosis and prognosis of future TV disease development. Appropriate surgical technique and timing still need to be clarified. PMID:22457188

Investigation of genesis of gallop sounds in dogs by quantitative phonocardiography and digital frequency analysis.

PubMed

Aubert, A E; Denys, B G; Meno, F; Reddy, P S

1985-05-01

Several investigators have noted external gallop sounds to be of higher amplitude than their corresponding internal sounds (S3 and S4). In this study we hoped to determine if S3 and S4 are transmitted in the same manner as S1. In 11 closed-chest dogs, external (apical) and left ventricular pressures and sounds were recorded simultaneously with transducers with identical sensitivity and frequency responses. Volume and pressure overload and positive and negative inotropic drugs were used to generate gallop sounds. Recordings were made in the control state and after the various interventions. S3 and S4 were recorded in 17 experiments each. The amplitude of the external S1 was uniformly higher than that of internal S1 and internal gallop sounds were inconspicuous. With use of Fourier transforms, the gain function was determined by comparing internal to external S1. By inverse transform, the amplitude of the internal gallop sounds was predicted from external sounds. The internal sounds of significant amplitude were predicted in many instances, but the actual recordings showed no conspicuous sounds. The absence of internal gallop sounds of expected amplitude as calculated from the external gallop sounds and the gain function derived from the comparison of internal and external S1 make it very unlikely that external gallop sounds are derived from internal sounds.

Tricuspid valve and percutaneous approach: No longer the forgotten valve!

PubMed

Bouleti, Claire; Juliard, Jean-Michel; Himbert, Dominique; Iung, Bernard; Brochet, Eric; Urena, Marina; Dilly, Marie-Pierre; Ou, Phalla; Nataf, Patrick; Vahanian, Alec

2016-01-01

Tricuspid valve disease is mainly represented by tricuspid regurgitation (TR), which is a predictor of poor outcome. TR is usually secondary, caused by right ventricle pressure or volume overload, the leading cause being left-sided heart valve diseases. Tricuspid surgery for severe TR is recommended during left valve surgery, and consists of either a valve replacement or, most often, a tricuspid repair with or without prosthetic annuloplasty. When TR persists or worsens after left valvular surgery, redo isolated tricuspid surgery is associated with high mortality. In addition, a sizeable proportion of patients present with tricuspid surgery deterioration over time, and need a reintervention, which is associated with high morbi-mortality rates. In this context, and given the recent major breakthrough in the percutaneous treatment of aortic and mitral valve diseases, the tricuspid valve appears an appealing challenge, although it raises specific issues. The first applications of transcatheter techniques for tricuspid valve disease were valve-in-valve and valve-in-ring implantation for degenerated bioprosthesis or ring annuloplasty. Some concerns remain regarding prosthesis sizing, rapid ventricular pacing and the best approach, but these procedures appear to be safe and effective. More recently, bicuspidization using a transcatheter approach for the treatment of native tricuspid valve has been published, in two patients. Finally, other devices are in preclinical development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Evaluation of changes in left ventricular structure and function in hypertensive patients with coronary artery disease after PCI using real-time three-dimensional echocardiography.

PubMed

Meng, Yanhong; Zong, Ling; Zhang, Ziteng; Han, Youdong; Wang, Yanhui

2018-02-01

We aimed to evaluate the changes in left ventricular structure and function in hypertensive patients with coronary artery disease before and after percutaneous coronary intervention (PCI) using real-time three-dimensional echocardiography. Two hundred and eighty hypertensive patients with coronary artery disease undergoing PCI and 120 cases who did not receive PCI in our hospital were selected as the subjects of our study. All patients were administered with routine antiplatelet, anticoagulant, lipid-lowering, antihypertensive, dilating coronary artery and other medications. The left ventricular systolic function and systolic synchrony index changes before and after subjects were treated by PCI were analyzed using three-dimensional echocardiography. At 2 days before surgery, there were no significant differences in the left ventricular end-diastolic volume, left ventricular end-systolic volume (LVESV) and ejection fraction (EF) between the two patient groups (P>0.05). At 3 months and 9 months, the two key time points after PCI, the LVESV level in the PCI group was distinctly decreased, while EF was significantly increased (P<0.05). In addition, before treatment, there were no significant differences in the parameters of time from the corresponding segment of the myocardium to the minimal systolic volume in two patient groups, such as Tmsv-16SD, Tmsv-16Dif, Tmsv-12SD, Tmsv-12Dif, Tmsv-6SD and Tmsv-6Dif (P>0.05); however, the parameters of time from the corresponding segment of the myocardium to the minimal systolic volume in patients in the PCI group were significantly reduced at 3 and 9 months after surgery (P<0.05). Three-dimensional echocardiography can evaluate the critical parameters in the prognosis of hypertensive patients with coronary artery disease after PCI accurately and in real-time, which may play a significant role.

Evidence for increased cardiac compliance during exposure to simulated microgravity

NASA Technical Reports Server (NTRS)

Koenig, S. C.; Convertino, V. A.; Fanton, J. W.; Reister, C. A.; Gaffney, F. A.; Ludwig, D. A.; Krotov, V. P.; Trambovetsky, E. V.; Latham, R. D.

1998-01-01

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

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.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance.

PubMed

Smedema, Jan-Peter; van Geuns, Robert-Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J G M

2017-11-01

Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast-enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast-enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non-invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

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

Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock.

PubMed

Kumar, Anand; Schupp, Elizabeth; Bunnell, Eugene; Ali, Amjad; Milcarek, Barry; Parrillo, Joseph E

2008-01-01

During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock. A prospective, non-randomised, non-blinded interventional study of graded dobutamine challenge (0, 5, 10, and 15 mug/kg/min) in adult patients who had undergone pulmonary artery catheterisation within 48 hours of onset of severe sepsis or septic shock (8 survivors/15 non-survivors) was performed. Radionuclide cineangiography during graded infusion was used to determine biventricular ejection fractions at each increment of dobutamine. In univariate analysis, a variety of cardiovascular or haemodynamic and oxygen transport or metabolic variables (at the point of maximum cardiac index response for a given subject) were associated with survival including: increased stroke volume index (p = 0.0003); right ventricular end-diastolic volume index (p = 0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left ventricular end-systolic volume index ratio (p = 0.0188); left ventricular ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p = 0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5 mL/m2 were concordant with survival or death in 21 of 23 cases. Multivariate profile construction showed stroke volume index as the dominant discriminating variable for survival with the systolic blood pressure/left ventricular end-systolic volume index ratio alone among all other variables significantly improving the model. Survivors maintain cardiac responsiveness to catecholamine stimulation during septic shock. Survival from severe sepsis or septic shock is associated with increased cardiac performance and contractility indices during dobutamine infusion. Further studies are required to determine whether these parameters are predictive of outcome in a larger severe sepsis/septic shock population.

Quantitative computed tomography of pulmonary emphysema and ventricular function in chronic obstructive pulmonary disease patients with pulmonary hypertension.

PubMed

Huang, Yu-Sen; Hsu, Hsao-Hsun; Chen, Jo-Yu; Tai, Mei-Hwa; Jaw, Fu-Shan; Chang, Yeun-Chung

2014-01-01

This study strived to evaluate the relationship between degree of pulmonary emphysema and cardiac ventricular function in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) using electrocardiographic-gated multidetector computed tomography (CT). Lung transplantation candidates with the diagnosis of COPD and PH were chosen for the study population, and a total of 15 patients were included. The extent of emphysema is defined as the percentage of voxels below -910 Hounsfield units in the lung windows in whole lung CT without intravenous contrast. Heart function parameters were measured by electrocardiographic-gated CT angiography. Linear regression analysis was conducted to examine the associations between percent emphysema and heart function indicators. Significant correlations were found between percent emphysema and right ventricular (RV) measurements, including RV end-diastolic volume (R(2) = 0.340, p = 0.023), RV stroke volume (R(2) = 0.406, p = 0.011), and RV cardiac output (R(2) = 0.382, p = 0.014); the correlations between percent emphysema and left ventricular function indicators were not observed. The study revealed that percent emphysema is correlated with RV dysfunction among COPD patients with PH. Based on our findings, percent emphysema can be considered for use as an indicator to predict the severity of right ventricular dysfunction among COPD patients.

Use of a Doppler pulmonary artery catheter for continuous measurement of right ventricular pump function and contractility during single lung transplantation.

PubMed

Heerdt, P M; Pond, C G; Kussman, M K; Triantafillou, A N

1993-01-01

Despite numerous technologic advances in intraoperative monitoring, the only methods routinely available for assessment of right ventricular function in lung transplant recipients are continuous measurement of right heart pressures and intermittent thermodilution determination of cardiac output and ejection fraction. Additional data may now be obtained with transesophageal echocardiography, although this technology is expensive and not widely available and requires diverting attention from a potentially unstable patient for data acquisition and analysis. Recently, a Doppler pulmonary artery catheter was introduced that measures beat-to-beat pulmonary artery blood flow-velocity, cross sectional area, and volume flow. Because of data indicating that acceleration of blood in the pulmonary artery (measured as the first derivative of either the velocity or flow waveform) is a sensitive indicator of right ventricular contractility, we have used waveforms obtained with the catheter for assessment of right ventricular pump function (stroke volume and peak pulmonary artery flow rate) and contractility in heart surgery patients. We report here our experience with this method in two patients undergoing left single lung transplantation.

Investigating structural brain changes of dehydration using voxel-based morphometry.

PubMed

Streitbürger, Daniel-Paolo; Möller, Harald E; Tittgemeyer, Marc; Hund-Georgiadis, Margret; Schroeter, Matthias L; Mueller, Karsten

2012-01-01

Dehydration can affect the volume of brain structures, which might imply a confound in volumetric and morphometric studies of normal or diseased brain. Six young, healthy volunteers were repeatedly investigated using three-dimensional T(1)-weighted magnetic resonance imaging during states of normal hydration, hyperhydration, and dehydration to assess volume changes in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The datasets were analyzed using voxel-based morphometry (VBM), a widely used voxel-wise statistical analysis tool, FreeSurfer, a fully automated volumetric segmentation measure, and SIENAr a longitudinal brain-change detection algorithm. A significant decrease of GM and WM volume associated with dehydration was found in various brain regions, most prominently, in temporal and sub-gyral parietal areas, in the left inferior orbito-frontal region, and in the extra-nuclear region. Moreover, we found consistent increases in CSF, that is, an expansion of the ventricular system affecting both lateral ventricles, the third, and the fourth ventricle. Similar degrees of shrinkage in WM volume and increase of the ventricular system have been reported in studies of mild cognitive impairment or Alzheimer's disease during disease progression. Based on these findings, a potential confound in GM and WM or ventricular volume studies due to the subjects' hydration state cannot be excluded and should be appropriately addressed in morphometric studies of the brain.

Investigating Structural Brain Changes of Dehydration Using Voxel-Based Morphometry

PubMed Central

Streitbürger, Daniel-Paolo; Möller, Harald E.; Tittgemeyer, Marc; Hund-Georgiadis, Margret; Schroeter, Matthias L.; Mueller, Karsten

2012-01-01

Dehydration can affect the volume of brain structures, which might imply a confound in volumetric and morphometric studies of normal or diseased brain. Six young, healthy volunteers were repeatedly investigated using three-dimensional T 1-weighted magnetic resonance imaging during states of normal hydration, hyperhydration, and dehydration to assess volume changes in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The datasets were analyzed using voxel-based morphometry (VBM), a widely used voxel-wise statistical analysis tool, FreeSurfer, a fully automated volumetric segmentation measure, and SIENAr a longitudinal brain-change detection algorithm. A significant decrease of GM and WM volume associated with dehydration was found in various brain regions, most prominently, in temporal and sub-gyral parietal areas, in the left inferior orbito-frontal region, and in the extra-nuclear region. Moreover, we found consistent increases in CSF, that is, an expansion of the ventricular system affecting both lateral ventricles, the third, and the fourth ventricle. Similar degrees of shrinkage in WM volume and increase of the ventricular system have been reported in studies of mild cognitive impairment or Alzheime s disease during disease progression. Based on these findings, a potential confound in GM and WM or ventricular volume studies due to the subjects’ hydration state cannot be excluded and should be appropriately addressed in morphometric studies of the brain. PMID:22952926

Right ventricular volumes assessed by echocardiographic three-dimensional knowledge-based reconstruction compared with magnetic resonance imaging in a clinical setting.

PubMed

Neukamm, Christian; Try, Kirsti; Norgård, Gunnar; Brun, Henrik

2014-01-01

A technique that uses two-dimensional images to create a knowledge-based, three-dimensional model was tested and compared to magnetic resonance imaging. Measurement of right ventricular volumes and function is important in the follow-up of patients after pulmonary valve replacement. Magnetic resonance imaging is the gold standard for volumetric assessment. Echocardiographic methods have been validated and are attractive alternatives. Thirty patients with tetralogy of Fallot (25 ± 14 years) after pulmonary valve replacement were examined. Magnetic resonance imaging volumetric measurements and echocardiography-based three-dimensional reconstruction were performed. End-diastolic volume, end-systolic volume, and ejection fraction were measured, and the results were compared. Magnetic resonance imaging measurements gave coefficient of variation in the intraobserver study of 3.5, 4.6, and 5.3 and in the interobserver study of 3.6, 5.9, and 6.7 for end-diastolic volume, end-systolic volume, and ejection fraction, respectively. Echocardiographic three-dimensional reconstruction was highly feasible (97%). In the intraobserver study, the corresponding values were 6.0, 7.0, and 8.9 and in the interobserver study 7.4, 10.8, and 13.4. In comparison of the methods, correlations with magnetic resonance imaging were r = 0.91, 0.91, and 0.38, and the corresponding coefficient of variations were 9.4, 10.8, and 14.7. Echocardiography derived volumes (mL/m(2)) were significantly higher than magnetic resonance imaging volumes in end-diastolic volume 13.7 ± 25.6 and in end-systolic volume 9.1 ± 17.0 (both P < .05). The knowledge-based three-dimensional right ventricular volume method was highly feasible. Intra and interobserver variabilities were satisfactory. Agreement with magnetic resonance imaging measurements for volumes was reasonable but unsatisfactory for ejection fraction. Knowledge-based reconstruction may replace magnetic resonance imaging measurements for serial follow-up, whereas magnetic resonance imaging should be used for surgical decision making.

Clinical review: Positive end-expiratory pressure and cardiac output

PubMed Central

Luecke, Thomas; Pelosi, Paolo

2005-01-01

In patients with acute lung injury, high levels of positive end-expiratory pressure (PEEP) may be necessary to maintain or restore oxygenation, despite the fact that 'aggressive' mechanical ventilation can markedly affect cardiac function in a complex and often unpredictable fashion. As heart rate usually does not change with PEEP, the entire fall in cardiac output is a consequence of a reduction in left ventricular stroke volume (SV). PEEP-induced changes in cardiac output are analyzed, therefore, in terms of changes in SV and its determinants (preload, afterload, contractility and ventricular compliance). Mechanical ventilation with PEEP, like any other active or passive ventilatory maneuver, primarily affects cardiac function by changing lung volume and intrathoracic pressure. In order to describe the direct cardiocirculatory consequences of respiratory failure necessitating mechanical ventilation and PEEP, this review will focus on the effects of changes in lung volume, factors controlling venous return, the diastolic interactions between the ventricles and the effects of intrathoracic pressure on cardiac function, specifically left ventricular function. Finally, the hemodynamic consequences of PEEP in patients with heart failure, chronic obstructive pulmonary disease and acute respiratory distress syndrome are discussed. PMID:16356246

Two-Dimensional Echocardiography Estimates of Fetal Ventricular Mass throughout Gestation.

PubMed

Aye, Christina Y L; Lewandowski, Adam James; Ohuma, Eric O; Upton, Ross; Packham, Alice; Kenworthy, Yvonne; Roseman, Fenella; Norris, Tess; Molloholli, Malid; Wanyonyi, Sikolia; Papageorghiou, Aris T; Leeson, Paul

2017-08-12

Two-dimensional (2D) ultrasound quality has improved in recent years. Quantification of cardiac dimensions is important to screen and monitor certain fetal conditions. We assessed the feasibility and reproducibility of fetal ventricular measures using 2D echocardiography, reported normal ranges in our cohort, and compared estimates to other modalities. Mass and end-diastolic volume were estimated by manual contouring in the four-chamber view using TomTec Image Arena 4.6 in end diastole. Nomograms were created from smoothed centiles of measures, constructed using fractional polynomials after log transformation. The results were compared to those of previous studies using other modalities. A total of 294 scans from 146 fetuses from 15+0 to 41+6 weeks of gestation were included. Seven percent of scans were unanalysable and intraobserver variability was good (intraclass correlation coefficients for left and right ventricular mass 0.97 [0.87-0.99] and 0.99 [0.95-1.0], respectively). Mass and volume increased exponentially, showing good agreement with 3D mass estimates up to 28 weeks of gestation, after which our measurements were in better agreement with neonatal cardiac magnetic resonance imaging. There was good agreement with 4D volume estimates for the left ventricle. Current state-of-the-art 2D echocardiography platforms provide accurate, feasible, and reproducible fetal ventricular measures across gestation, and in certain circumstances may be the modality of choice. © 2017 S. Karger AG, Basel.

Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia.

PubMed

Kingma, J G; Linderoth, B; Ardell, J L; Armour, J A; DeJongste, M J; Foreman, R D

2001-08-13

Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure-volume loops. SCS was accomplished by stimulating the dorsal T1-T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure-volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure-volume dynamics in the anesthetized experimental preparation.

[Sodium hydrosulfide improves cardiac functions and structures in rats with chronic heart failure].

PubMed

Li, Xiao-hui; Zhang, Chao-ying; Zhang, Ting

2011-11-22

To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling. A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared. At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P < 0.05, 1 mm Hg = 0.133 kPa). The RV peak rate of contraction and relaxation markedly decreased (RV ± dp/dt max) (mm Hg/s: 1528 ± 113 vs 2336 ± 185 and 1835 ± 132, 1331 ± 107 vs 2213 ± 212 and 1768 ± 116, all P < 0.05). It was found microscopically that myocardial fibers in the shunt group were irregularly arranged, partially cytolysis and infiltrated by inflammatory cells. Electron microscopy revealed that myocardial fibers thickened non-uniformly in the shunt group, some fiber mitochondria were highly swollen and contained vacuoles. And sarcoplasmic reticulum appeared slightly dilated. Polarized microscopy indicated that, collagen content (particularly type-I collagen) increased in the shunt group compared with the sham operation group. Additionally, compared with the shunt group, the shunt and NaHS treatment groups showed an amelioration of myocardial damage, an alleviation of myocardial fiber changes and a decrease in myocardial collagen content (particularly type-I collagen). Compared with the sham operation and shunt + NaHS groups, the shunt group displayed increased right ventricular hydroxyproline (mg×g(-1)·pro: 1.32 ± 0.25 vs 0.89 ± 0.18 and 0.83 ± 0.19, all P < 0.05). H(2)S may improve cardiac functions and ameliorate cardiac structures in rats with chronic heart failure probably through dilating the blood vessels and affecting the extracellular collagen metabolism.

Reduction of ventricular size after shunting for normal pressure hydrocephalus related to CSF dynamics before shunting.

PubMed Central

Tans, J T; Poortvliet, D C

1988-01-01

Reduction of ventricular size was determined by repeated computed tomography in 30 adult patients shunted for normal pressure hydrocephalus (NPH) and related to the pressure-volume index (PVI) and resistance to outflow of cerebrospinal fluid (Rcsf) measured before shunting. Rapid and marked reduction of ventricular size (n = 10) was associated with a significantly lower PVI than slow and moderate to marked (n = 13) or minimal to mild reduction (n = 7). Otherwise no relationship could be found between the reduction of ventricular size and PVI or Rcsf. It is concluded that both rate and magnitude of reduction of ventricular size after shunting for NPH are extremely variable. High brain elasticity seems to be the best predictor of rapid and marked reduction. PMID:3379425

Successful Feasibility Human Trial of a New Self-Expandable Percutaneous Pulmonary Valve (Pulsta Valve) Implantation Using Knitted Nitinol Wire Backbone and Trileaflet α-Gal-Free Porcine Pericardial Valve in the Native Right Ventricular Outflow Tract.

PubMed

Kim, Gi Beom; Song, Mi Kyoung; Bae, Eun Jung; Park, Eun-Ah; Lee, Whal; Lim, Hong-Gook; Kim, Yong Jin

2018-06-01

Self-expandable percutaneous pulmonary valve implantation (PPVI) for native right ventricular outflow tract lesions is still in the clinical trial phase. The aim of this study is to present the result of feasibility study of a novel self-expandable knitted nitinol wire stent mounted with a treated trileaflet α-Gal-free porcine pericardial valve for PPVI. A feasibility study using Pulsta valve (TaeWoong Medical Co, Gyeonggi-do, South Korea) was designed for patients with severe pulmonary regurgitation in the native right ventricular outflow tract, and 6-month follow-up outcomes were reviewed. Ten tetralogy of Fallot patients were enrolled. Before PPVI, severe pulmonary regurgitation (mean pulmonary regurgitation fraction, 45.5%±7.2%; range, 34.9%-56%) and enlarged right ventricular volume (mean indexed right ventricular end-diastolic volume, 176.7±14.3 mL/m 2 ; range, 158.9-205.9 mL/m 2 ) were present. The median age at PPVI was 21.7±6.5 years (range, 13-36 years). Five patients were successfully implanted with 28 mm and the other 5 with 26 mm valves loaded on the 18F delivery cable. No significant periprocedural complications were noted in any patient. At the 6-month follow-up, indexed right ventricular end-diastolic volume was dramatically decreased to 126.3±20.3 mL/m 2 (range, 99-164.2 mL/m 2 ), and the mean value of peak instantaneous pressure gradient between the right ventricle and the pulmonary artery decreased from 6.8±3.5 mm Hg (range, 2-12 mm Hg) before PPVI to 5.7±6.7 mm Hg (range, 2-12 mm Hg) without significant pulmonary regurgitation. There was no adverse event associated with the valve. A feasibility study of the Pulsta valve for native right ventricular outflow tract lesions was completed successfully with planned Pulsta valve implantation and demonstrated good short-term effectiveness without serious adverse events. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02555319. © 2018 American Heart Association, Inc.

Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears.

PubMed

Nelson, O Lynne; Robbins, Charles T; Wu, Yiming; Granzier, Henk

2008-07-01

The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 +/- 12 compared with 402 +/- 14 g; P = 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 +/- 14 compared with 143.2 +/- 20 ms; P = 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 +/- 0.07 in the active bears and decreased to 0.42 +/- 0.03 (P = 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly bears.

Analysis of transthoracic echocardiographic data in major vascular surgery from a prospective randomised trial comparing sevoflurane and fentanyl with propofol and remifentanil anaesthesia.

PubMed

Lindholm, E E; Aune, E; Frøland, G; Kirkebøen, K A; Otterstad, J E

2014-06-01

The aim of this study was to define pre-operative echocardiographic data and explore if postoperative indices of cardiac function after open abdominal aortic surgery were affected by the anaesthetic regimen. We hypothesised that volatile anaesthesia would improve indices of cardiac function compared with total intravenous anaesthesia. Transthoracic echocardiography was performed pre-operatively in 78 patients randomly assigned to volatile anaesthesia and 76 to total intravenous anaesthesia, and compared with postoperative data. Pre-operatively, 16 patients (10%) had left ventricular ejection fraction < 46%. In 138 patients with normal left ventricular ejection fraction, 5/8 (62%) with left ventricular dilatation and 41/130 (33%) without left ventricular dilatation had evidence of left ventricular diastolic dysfunction (p < 0.001). Compared with pre-operative findings, significant increases in left ventricular end-diastolic volume, left atrial maximal volume, cardiac output, velocity of early mitral flow and early myocardial relaxation occurred postoperatively (all p < 0.001). The ratio of the velocity of early mitral flow to early myocardial relaxation remained unchanged. There were no significant differences in postoperative echocardiographic findings between patients anaesthetised with volatile anaesthesia or total intravenous anaesthesia. Patients had an iatrogenic surplus of approximately 4.1 l of fluid volume by the first postoperative day. N-terminal prohormone of brain natriuretic peptide increased on the first postoperative day (p < 0.001) and remained elevated after 30 days (p < 0.001) in both groups. Although postoperative echocardiographic alterations were most likely to be related to increased preload due to a substantial iatrogenic surplus of fluid, a component of peri-operative myocardial ischaemia cannot be excluded. Our hypothesis that volatile anaesthesia improved indices of cardiac function compared with total intravenous anaesthesia could not be verified. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Propionyl-L-carnitine limits chronic ventricular dilation after myocardial infarction in rats.

PubMed

Micheletti, R; Di Paola, E D; Schiavone, A; English, E; Benatti, P; Capasso, J M; Anversa, P; Bianchi, G

1993-04-01

To determine whether propionyl-L-carnitine (PLC) administration ameliorates ventricular remodeling after myocardial infarction, we performed coronary occlusion in rats and examined the long-term effects of the drug 19-24 wk after surgery. In view of the well-established role of angiotensin-converting enzyme (ACE) inhibitors in the reduction of ventricular dilation after infarction, the therapeutic impact of oral PLC (60 mg/kg) was compared with that of enalapril (1 mg/kg). Infarct size measured planimetrically was found to be comparable in untreated, PLC-treated, and enalapril-treated rats, averaging 40-46% of the left ventricular free wall. Heart weight was increased 14, 16, and 11% with no treatment, with PLC, and with enalapril, respectively. The relationship between left ventricular filling pressure and chamber volume demonstrated that PLC and enalapril significantly prevented the expansion in cavitary size after infarction. These protective influences were observed throughout the range of filling pressures measured, from 0 to 30 mmHg. At a uniform reference point of filling pressure of 4 mmHg, untreated infarcted hearts showed an expansion in ventricular volume of 2.17-fold (P < 0.0001). Corresponding increases in this parameter after PLC and enalapril were 36 and 43%, respectively, both not statistically significant. Moreover, PLC was capable of reducing the alterations in myocardial compliance associated with myocardial infarction. In conclusion, PLC reduces the magnitude of decompensated eccentric hypertrophy produced by myocardial infarction in a manner similar to that found with ACE inhibition.

Deterioration of left ventricular chamber performance after bed rest : "cardiovascular deconditioning" or hypovolemia?

NASA Technical Reports Server (NTRS)

Perhonen, M. A.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

2001-01-01

BACKGROUND: Orthostatic intolerance after bed rest is characterized by hypovolemia and an excessive reduction in stroke volume (SV) in the upright position. We studied whether the reduction in SV is due to a specific adaptation of the heart to head-down tilt bed rest (HDTBR) or acute hypovolemia alone. METHODS AND RESULTS: We constructed left ventricular (LV) pressure-volume curves from pulmonary capillary wedge pressure and LV end-diastolic volume and Starling curves from pulmonary capillary wedge pressure and SV during lower body negative pressure and saline loading in 7 men (25+/-2 years) before and after 2 weeks of -6 degrees HDTBR and after the acute administration of intravenous furosemide. Both HDTBR and hypovolemia led to a similar reduction in plasma volume. However, baseline LV end-diastolic volume decreased by 20+/-4% after HDTBR and by 7+/-2% after hypovolemia (interaction P<0.001). Moreover, SV was reduced more and the Starling curve was steeper during orthostatic stress after HDTBR than after hypovolemia. The pressure-volume curve showed a leftward shift and the equilibrium volume of the left ventricle was decreased after HDTBR; however, after hypovolemia alone, the curve was identical, with no change in equilibrium volume. Lower body negative pressure tolerance was reduced after both conditions; it decreased by 27+/-7% (P<0.05) after HDTBR and by 18+/-8% (P<0.05) after hypovolemia. CONCLUSIONS: Chronic HDTBR leads to ventricular remodeling, which is not seen with equivalent degrees of acute hypovolemia. This remodeling leads to a greater decrease in SV during orthostatic stress after bed rest than hypovolemia alone, potentially contributing to orthostatic intolerance.

Impairment of left ventricular function during coronary angioplastic occlusion evaluated with a nonimaging scintillation probe.

PubMed

Hartmann, A; Maul, F D; Zimny, M; Klepzig, H; Vallbracht, C; Kneissl, H G; Schräder, R; Hör, G; Kaltenbach, M

1991-09-01

Impairment of left ventricular function during controlled myocardial ischemia induced by coronary angioplasty has been reported from angiographic and echocardiographic studies. Ejection fraction, peak ejection, peak filling rates, and end-systolic and end-diastolic volumes were investigated before, during and after coronary occlusion on-line with a nonimaging scintillation probe. The study consisted of 18 patients (mean age 59 +/- 10 years) with coronary artery stenosis of greater than 70%. During balloon inflation of 60 seconds' duration, coronary occlusion pressure was 31.6 +/- 12 mm Hg. There was no significant change in heart rate. Delay between first and second dilatation was 109 +/- 63 seconds. Ejection fraction decreased from 53 +/- 16 to 40 +/- 12% (first dilatation, p less than 0.01) and to 39 +/- 14% (second dilatation, p less than 0.01) and recovered to 51 +/- 16% 5 minutes after the second dilatation. Peak ejection rate was significantly reduced during the first and second balloon inflations. Peak filling rate decreased from 2.5 +/- 0.8 to 2.0 +/- 0.7 end-diastolic volume.s-1 (first dilatation, p less than 0.01) and to 1.8 +/- 0.7 end-diastolic volume.s-1 (second dilatation, p less than 0.01) and remained reduced at 2.2 +/- 0.7 end-diastolic volume.s-1 (p = not significant) at 5 minutes after the second dilatation. End-systolic and end-diastolic volumes increased significantly during the first and second dilatations and returned to normal after dilatation. It is concluded that short, controlled myocardial ischemia during coronary angioplasty leads to a decrease in systolic and diastolic left ventricular function. Sequential dilatations do not further decrease function if a sufficient interval is kept.

Biomechanical and Hemodynamic Measures of Right Ventricular Diastolic Function: Translating Tissue Biomechanics to Clinical Relevance.

PubMed

Jang, Sae; Vanderpool, Rebecca R; Avazmohammadi, Reza; Lapshin, Eugene; Bachman, Timothy N; Sacks, Michael; Simon, Marc A

2017-09-12

Right ventricular (RV) diastolic function has been associated with outcomes for patients with pulmonary hypertension; however, the relationship between biomechanics and hemodynamics in the right ventricle has not been studied. Rat models of RV pressure overload were obtained via pulmonary artery banding (PAB; control, n=7; PAB, n=5). At 3 weeks after banding, RV hemodynamics were measured using a conductance catheter. Biaxial mechanical properties of the RV free wall myocardium were obtained to extrapolate longitudinal and circumferential elastic modulus in low and high strain regions (E 1 and E 2 , respectively). Hemodynamic analysis revealed significantly increased end-diastolic elastance (E ed ) in PAB (control: 55.1 mm Hg/mL [interquartile range: 44.7-85.4 mm Hg/mL]; PAB: 146.6 mm Hg/mL [interquartile range: 105.8-155.0 mm Hg/mL]; P =0.010). Longitudinal E 1 was increased in PAB (control: 7.2 kPa [interquartile range: 6.7-18.1 kPa]; PAB: 34.2 kPa [interquartile range: 18.1-44.6 kPa]; P =0.018), whereas there were no significant changes in longitudinal E 2 or circumferential E 1 and E 2 . Last, wall stress was calculated from hemodynamic data by modeling the right ventricle as a sphere: stress=Pressure×radius2×thickness. RV pressure overload in PAB rats resulted in an increase in diastolic myocardial stiffness reflected both hemodynamically, by an increase in E ed , and biomechanically, by an increase in longitudinal E 1 . Modest increases in tissue biomechanical stiffness are associated with large increases in E ed . Hemodynamic measurements of RV diastolic function can be used to predict biomechanical changes in the myocardium. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Reducing endoglin activity limits calcineurin and TRPC-6 expression and improves survival in a mouse model of right ventricular pressure overload.

PubMed

Kapur, Navin K; Qiao, Xiaoying; Paruchuri, Vikram; Mackey, Emily E; Daly, Gerard H; Ughreja, Kishan; Ughreja, Keshan; Morine, Kevin J; Levine, Jonathan; Aronovitz, Mark J; Hill, Nicholas S; Jaffe, Iris Z; Letarte, Michelle; Karas, Richard H

2014-07-11

Right ventricular (RV) failure is a major cause of mortality worldwide and is often a consequence of RV pressure overload (RVPO). Endoglin is a coreceptor for the profibrogenic cytokine, transforming growth factor beta 1 (TGF-β1). TGF-β1 signaling by the canonical transient receptor protein channel 6 (TRPC-6) was recently reported to stimulate calcineurin-mediated myofibroblast transformation, a critical component of cardiac fibrosis. We hypothesized that reduced activity of the TGF-β1 coreceptor, endoglin, limits RV calcineurin expression and improves survival in RVPO. We first demonstrate that endoglin is required for TGF-β1-mediated calcineurin/TRPC-6 expression and up-regulation of alpha-smooth muscle antigen (α-SMA), a marker of myofibroblast transformation, in human RV fibroblasts. Using endoglin haploinsufficient mice (Eng(+/-)) we show that reduced endoglin activity preserves RV function, limits RV fibrosis, and attenuates activation of the calcineurin/TRPC-6/α-SMA pathway in a model of angio-obliterative pulmonary hypertension. Next, using Eng(+/-) mice or a neutralizing antibody (Ab) against endoglin (N-Eng) in wild-type mice, we show that reduced endoglin activity improves survival and attenuates RV fibrosis in models of RVPO induced by pulmonary artery constriction. To explore the utility of targeting endoglin, we observed a reversal of RV fibrosis and calcineurin levels in wild-type mice treated with a N-Eng Ab, compared to an immunoglobulin G control. These data establish endoglin as a regulator of TGF-β1 signaling by calcineurin and TRPC-6 in the RV and identify it as a potential therapeutic target to limit RV fibrosis and improve survival in RVPO, a common cause of death in cardiac and pulmonary disease. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Standard and Strain Measurements by Echocardiography Detect Early Overloaded Right Ventricular Dysfunction: Validation against Hemodynamic and Myocyte Contractility Changes in a Large Animal Model.

PubMed

Hodzic, Amir; Bobin, Pierre; Mika, Delphine; Ly, Mohamed; Lefebvre, Florence; Lechêne, Patrick; Le Bret, Emmanuel; Gouadon, Elodie; Coblence, Mathieu; Vandecasteele, Grégoire; Capderou, André; Leroy, Jérôme; Rucker-Martin, Catherine; Lambert, Virginie

2017-11-01

Early detection of right ventricular (RV) failure is required to improve the management of patients with congenital heart diseases. The aim of this study was to validate echocardiography for the early detection of overloaded RV dysfunction, compared with hemodynamic and myocyte contractility assessment. Using a porcine model reproducing repaired tetralogy of Fallot, RV function was evaluated over 4 months using standard echocardiography and speckle-tracking compared with hemodynamic parameters (conductance catheter). Sarcomere shortening and calcium transients were recorded in RV isolated myocytes. Contractile reserve (ΔE max ) was assessed by β-adrenergic stimulation in vivo (dobutamine 5 μg/kg) and ex vivo (isoproterenol 100 nM). Six operated animals were compared with four age- and sex-matched controls. In the operated group, hemodynamic RV efficient ejection fraction was significantly decreased (29.7% [26.2%-34%] vs 42.9% [40.7%-48.6%], P < .01), and inotropic responses to dobutamine were attenuated (ΔE max was 51% vs 193%, P < .05). Echocardiographic measurements of fraction of area change, tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity (S') and RV free wall longitudinal systolic strain and strain rate were significantly decreased. Strain rate, S', and tricuspid annular plane systolic excursion were correlated with ΔE max (r = 0.75, r = 0.78, and r = 0.65, respectively, P < .05). These alterations were associated in RV isolated myocytes with the decrease of sarcomere shortening in response to isoproterenol and perturbations of calcium homeostasis assessed by the increase of spontaneous calcium waves. In this porcine model, both standard and strain echocardiographic parameters detected early impairments of RV function and cardiac reserve, which were associated with cardiomyocyte excitation-contraction coupling alterations. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Miso (Japanese soybean paste) soup attenuates salt-induced sympathoexcitation and left ventricular dysfunction in mice with chronic pressure overload.

PubMed

Ito, Koji; Hirooka, Yoshitaka; Sunagawa, Kenji

2014-02-01

The hypothalamic mineralocorticoid receptor (MR)-angiotensin II type 1 receptor (AT1R) pathway is activated in mice with chronic pressure overload (CPO). When this activation is combined with high salt intake, it leads to sympathoexcitation, hypertension, and left ventricular (LV) dysfunction. Salt intake is thus an important factor that contributes to heart failure. Miso, a traditional Japanese food made from fermented soybeans, rice, wheat, or oats, can attenuate salt-induced hypertension in rats. However, its effects on CPO mice with salt-induced sympathoexcitation and LV dysfunction are unclear. Here, we investigated whether miso has protective effects in these mice. We also evaluated mechanisms associated with the hypothalamic MR-AT1R pathway. Aortic banding was used to produce CPO, and a sham operation was performed for controls. At 2 weeks after surgery, the mice were given water containing high NaCl levels (0.5%, 1.0%, and 1.5%) for 4 weeks. The high salt loading in CPO mice increased excretion of urinary norepinephrine (uNE), a marker of sympathetic activity, in an NaCl concentration-dependent manner; however, this was not observed in Sham mice. Subsequently, CPO mice were administered 1.0% NaCl water (CPO-H) or miso soup (1.0% NaCl equivalent, CPO-miso). The expression of hypothalamic MR, serum glucocorticoid-induced kinase-1 (SGK-1), and AT1R was higher in the CPO-H mice than in the Sham mice; however, the expression of these proteins was attenuated in the CPO-miso group. Although the CPO-miso mice had higher sodium intake, salt-induced sympathoexcitation was lower in these mice than in the CPO-H group. Our findings indicate that regular intake of miso soup attenuates salt-induced sympathoexcitation in CPO mice via inhibition of the hypothalamic MR-AT1R pathway.

A model of cardiac ryanodine receptor gating predicts experimental Ca2+-dynamics and Ca2+-triggered arrhythmia in the long QT syndrome

NASA Astrophysics Data System (ADS)

Wilson, Dan; Ermentrout, Bard; Němec, Jan; Salama, Guy

2017-09-01

Abnormal Ca2+ handling is well-established as the trigger of cardiac arrhythmia in catecholaminergic polymorphic ventricular tachycardia and digoxin toxicity, but its role remains controversial in Torsade de Pointes (TdP), the arrhythmia associated with the long QT syndrome (LQTS). Recent experimental results show that early afterdepolarizations (EADs) that initiate TdP are caused by spontaneous (non-voltage-triggered) Ca2+ release from Ca2+-overloaded sarcoplasmic reticulum (SR) rather than the activation of the L-type Ca2+-channel window current. In bradycardia and long QT type 2 (LQT2), a second, non-voltage triggered cytosolic Ca2+ elevation increases gradually in amplitude, occurs before overt voltage instability, and then precedes the rise of EADs. Here, we used a modified Shannon-Puglisi-Bers model of rabbit ventricular myocytes to reproduce experimental Ca2+ dynamics in bradycardia and LQT2. Abnormal systolic Ca2+-oscillations and EADs caused by SR Ca2+-release are reproduced in a modified 0-dimensional model, where 3 gates in series control the ryanodine receptor (RyR2) conductance. Two gates control RyR2 activation and inactivation and sense cytosolic Ca2+ while a third gate senses luminal junctional SR Ca2+. The model predicts EADs in bradycardia and low extracellular [K+] and cessation of SR Ca2+-release terminate salvos of EADs. Ca2+-waves, systolic cell-synchronous Ca2+-release, and multifocal diastolic Ca2+ release seen in subcellular Ca2+-mapping experiments are observed in the 2-dimensional version of the model. These results support the role of SR Ca2+-overload, abnormal SR Ca2+-release, and the subsequent activation of the electrogenic Na+/Ca2+-exchanger as the mechanism of TdP. The model offers new insights into the genesis of cardiac arrhythmia and new therapeutic strategies.

Investigating the Role of Interventricular Interdependence in Development of Right Heart Dysfunction During LVAD Support: A Patient-Specific Methods-Based Approach.

PubMed

Sack, Kevin L; Dabiri, Yaghoub; Franz, Thomas; Solomon, Scott D; Burkhoff, Daniel; Guccione, Julius M

2018-01-01

Predictive computation models offer the potential to uncover the mechanisms of treatments whose actions cannot be easily determined by experimental or imaging techniques. This is particularly relevant for investigating left ventricular mechanical assistance, a therapy for end-stage heart failure, which is increasingly used as more than just a bridge-to-transplant therapy. The high incidence of right ventricular failure following left ventricular assistance reflects an undesired consequence of treatment, which has been hypothesized to be related to the mechanical interdependence between the two ventricles. To investigate the implication of this interdependence specifically in the setting of left ventricular assistance device (LVAD) support, we introduce a patient-specific finite-element model of dilated chronic heart failure. The model geometry and material parameters were calibrated using patient-specific clinical data, producing a mechanical surrogate of the failing in vivo heart that models its dynamic strain and stress throughout the cardiac cycle. The model of the heart was coupled to lumped-parameter circulatory systems to simulate realistic ventricular loading conditions. Finally, the impact of ventricular assistance was investigated by incorporating a pump with pressure-flow characteristics of an LVAD (HeartMate II™ operating between 8 and 12 k RPM) in parallel to the left ventricle. This allowed us to investigate the mechanical impact of acute left ventricular assistance at multiple operating-speeds on right ventricular mechanics and septal wall motion. Our findings show that left ventricular assistance reduces myofiber stress in the left ventricle and, to a lesser extent, right ventricle free wall, while increasing leftward septal-shift with increased operating-speeds. These effects were achieved with secondary, potentially negative effects on the interventricular septum which showed that support from LVADs, introduces unnatural bending of the septum and with it, increased localized stress regions. Left ventricular assistance unloads the left ventricle significantly and shifts the right ventricular pressure-volume-loop toward larger volumes and higher pressures; a consequence of left-to-right ventricular interactions and a leftward septal shift. The methods and results described in the present study are a meaningful advancement of computational efforts to investigate heart-failure therapies in silico and illustrate the potential of computational models to aid understanding of complex mechanical and hemodynamic effects of new therapies.

Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure.

PubMed

Maier, Joscha; Sawall, Stefan; Kachelrieß, Marc

2014-05-01

Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levels from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the HDTV algorithm shows the best performance. At 50 mGy, the deviation from the reference obtained at 500 mGy were less than 4%. Also the LDPC algorithm provides reasonable results with deviation less than 10% at 50 mGy while PCF and MKB reconstruction show larger deviations even at higher dose levels. LDPC and HDTV increase CNR and allow for quantitative evaluations even at dose levels as low as 50 mGy. The left ventricular volumes exemplarily illustrate that cardiac parameters can be accurately estimated at lowest dose levels if sophisticated algorithms are used. This allows to reduce dose by a factor of 10 compared to today's gold standard and opens new options for longitudinal studies of the heart.

Assessment of dedicated low-dose cardiac micro-CT reconstruction algorithms using the left ventricular volume of small rodents as a performance measure

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

Maier, Joscha, E-mail: joscha.maier@dkfz.de; Sawall, Stefan; Kachelrieß, Marc

2014-05-15

Purpose: Phase-correlated microcomputed tomography (micro-CT) imaging plays an important role in the assessment of mouse models of cardiovascular diseases and the determination of functional parameters as the left ventricular volume. As the current gold standard, the phase-correlated Feldkamp reconstruction (PCF), shows poor performance in case of low dose scans, more sophisticated reconstruction algorithms have been proposed to enable low-dose imaging. In this study, the authors focus on the McKinnon-Bates (MKB) algorithm, the low dose phase-correlated (LDPC) reconstruction, and the high-dimensional total variation minimization reconstruction (HDTV) and investigate their potential to accurately determine the left ventricular volume at different dose levelsmore » from 50 to 500 mGy. The results were verified in phantom studies of a five-dimensional (5D) mathematical mouse phantom. Methods: Micro-CT data of eight mice, each administered with an x-ray dose of 500 mGy, were acquired, retrospectively gated for cardiac and respiratory motion and reconstructed using PCF, MKB, LDPC, and HDTV. Dose levels down to 50 mGy were simulated by using only a fraction of the projections. Contrast-to-noise ratio (CNR) was evaluated as a measure of image quality. Left ventricular volume was determined using different segmentation algorithms (Otsu, level sets, region growing). Forward projections of the 5D mouse phantom were performed to simulate a micro-CT scan. The simulated data were processed the same way as the real mouse data sets. Results: Compared to the conventional PCF reconstruction, the MKB, LDPC, and HDTV algorithm yield images of increased quality in terms of CNR. While the MKB reconstruction only provides small improvements, a significant increase of the CNR is observed in LDPC and HDTV reconstructions. The phantom studies demonstrate that left ventricular volumes can be determined accurately at 500 mGy. For lower dose levels which were simulated for real mouse data sets, the HDTV algorithm shows the best performance. At 50 mGy, the deviation from the reference obtained at 500 mGy were less than 4%. Also the LDPC algorithm provides reasonable results with deviation less than 10% at 50 mGy while PCF and MKB reconstruction show larger deviations even at higher dose levels. Conclusions: LDPC and HDTV increase CNR and allow for quantitative evaluations even at dose levels as low as 50 mGy. The left ventricular volumes exemplarily illustrate that cardiac parameters can be accurately estimated at lowest dose levels if sophisticated algorithms are used. This allows to reduce dose by a factor of 10 compared to today's gold standard and opens new options for longitudinal studies of the heart.« less

Short-time-scale left ventricular systolic dynamics. Evidence for a common mechanism in both left ventricular chamber and heart muscle mechanics.

PubMed

Campbell, K B; Shroff, S G; Kirkpatrick, R D

1991-06-01

Based on the premise that short-time-scale, small-amplitude pressure/volume/outflow behavior of the left ventricular chamber was dominated by dynamic processes originating in cardiac myofilaments, a prototype model was built to predict pressure responses to volume perturbations. In the model, chamber pressure was taken to be the product of the number of generators in a pressure-bearing state and their average volumetric distortion, as in the muscle theory of A.F. Huxley, in which force was equal to the number of attached crossbridges and their average lineal distortion. Further, as in the muscle theory, pressure generators were assumed to cycle between two states, the pressure-bearing state and the non-pressure-bearing state. Experiments were performed in the isolated ferret heart, where variable volume decrements (0.01-0.12 ml) were removed at two commanded flow rates (flow clamps, -7 and -14 ml/sec). Pressure responses to volume removals were analyzed. Although the prototype model accounted for most features of the pressure responses, subtle but systematic discrepancies were observed. The presence or absence of flow and the magnitude of flow affected estimates of model parameters. However, estimates of parameters did not differ when the model was fitted to flow clamps with similar magnitudes of flows but different volume changes. Thus, prototype model inadequacies were attributed to misrepresentations of flow-related effects but not of volume-related effects. Based on these discrepancies, an improved model was built that added to the simple two-state cycling scheme, a pathway to a third state. This path was followed only in response to volume change. The improved model eliminated the deficiencies of the prototype model and was adequate in accounting for all observations. Since the template for the improved model was taken from the cycling crossbridge theory of muscle contraction, it was concluded that, in spite of the complexities of geometry, architecture, and regional heterogeneity of function and structure, crossbridge mechanisms dominated the short-time-scale dynamics of left ventricular chamber behavior.

Quantification of right ventricular volume in dogs: a comparative study between three-dimensional echocardiography and computed tomography with the reference method magnetic resonance imaging.

PubMed

Sieslack, Anne K; Dziallas, Peter; Nolte, Ingo; Wefstaedt, Patrick; Hungerbühler, Stephan O

2014-10-12

Right ventricular (RV) volume and function are important diagnostic and prognostic factors in dogs with primary or secondary right-sided heart failure. The complex shape of the right ventricle and its retrosternal position make the quantification of its volume difficult. For that reason, only few studies exist, which deal with the determination of RV volume parameters. In human medicine cardiac magnetic resonance imaging (CMRI) is considered to be the reference technique for RV volumetric measurement (Nat Rev Cardiol 7(10):551-563, 2010), but cardiac computed tomography (CCT) and three-dimensional echocardiography (3DE) are other non-invasive methods feasible for RV volume quantification. The purpose of this study was the comparison of 3DE and CCT with CMRI, the gold standard for RV volumetric quantification. 3DE showed significant lower and CCT significant higher right ventricular volumes than CMRI. Both techniques showed very good correlations (R > 0.8) with CMRI for the volumetric parameters end-diastolic volume (EDV) and end-systolic volume (ESV). Ejection fraction (EF) and stroke volume (SV) were not different when considering CCT and CMRI, whereas 3DE showed a significant higher EF and lower SV than CMRI. The 3DE values showed excellent intra-observer variability (<3%) and still acceptable inter-observer variability (<13%). CCT provides an accurate image quality of the right ventricle with comparable results to the reference method CMRI. CCT overestimates the RV volumes; therefore, it is not an interchangeable method, having the disadvantage as well of needing general anaesthesia. 3DE underestimated the RV-Volumes, which could be explained by the worse image resolution. The excellent correlation between the methods indicates a close relationship between 3DE and CMRI although not directly comparable. 3DE is a promising technique for RV volumetric quantification, but further studies in awake dogs and dogs with heart disease are necessary to evaluate its usefulness in veterinary cardiology.

Bioimpedance Spectroscopy for Assessment of Volume Status in Patients before and after General Anaesthesia

PubMed Central

Ernstbrunner, Matthäus; Kostner, Lisa; Kimberger, Oliver; Wabel, Peter; Säemann, Marcus; Markstaller, Klaus; Fleischmann, Edith; Kabon, Barbara; Hecking, Manfred

2014-01-01

Background Technically assisted assessment of volume status before surgery may be useful to direct intraoperative fluid administration. We therefore tested a recently developed whole-body bioimpedance spectroscopy device to determine pre- to postoperative fluid distribution. Methods Using a three-compartment physiologic tissue model, the body composition monitor (BCM, Fresenius Medical Care, Germany) measures total body fluid volume, extracellular volume, intracellular volume and fluid overload as surplus or deficit of ‘normal’ extracellular volume. BCM-measurements were performed before and after standardized general anaesthesia for gynaecological procedures (laparotomies, laparoscopies and vaginal surgeries). BCM results were blinded to the attending anaesthesiologist and data analysed using the 2-sided, paired Student’s t-test and multiple linear regression. Results In 71 females aged 45±15 years with body weight 67±13 kg and duration of anaesthesia 154±68 min, pre- to postoperative fluid overload increased from −0.7±1.1 L to 0.1±1.0 L, corresponding to −5.1±7.5% and 0.8±6.7% of normal extracellular volume, respectively (both p<0.001), after patients had received 1.9±0.9 L intravenous crystalloid fluid. Perioperative urinary excretion was 0.4±0.3 L. The increase in extracellular volume was paralleled by an increase in total body fluid volume, while intracellular volume increased only slightly and without reaching statistical significance (p = 0.15). Net perioperative fluid balance (administered fluid volume minus urinary excretion) was significantly associated with change in extracellular volume (r2 = 0.65), but was not associated with change in intracellular volume (r2 = 0.01). Conclusions Routine intraoperative fluid administration results in a significant, and clinically meaningful increase in the extracellular compartment. BCM-measurements yielded plausible results and may become useful to guide intraoperative fluid therapy in future studies. PMID:25360698

Greater fluid overload and lower interdialytic weight gain are independently associated with mortality in a large international hemodialysis population.

PubMed

Hecking, Manfred; Moissl, Ulrich; Genser, Bernd; Rayner, Hugh; Dasgupta, Indranil; Stuard, Stefano; Stopper, Andrea; Chazot, Charles; Maddux, Franklin W; Canaud, Bernard; Port, Friedrich K; Zoccali, Carmine; Wabel, Peter

2018-04-20

Fluid overload and interdialytic weight gain (IDWG) are discrete components of the dynamic fluid balance in haemodialysis patients. We aimed to disentangle their relationship, and the prognostic importance of two clinically distinct, bioimpedance spectroscopy (BIS)-derived measures, pre-dialysis and post-dialysis fluid overload (FOpre and FOpost) versus IDWG. We conducted a retrospective cohort study on 38 614 incident patients with one or more BIS measurement within 90 days of haemodialysis initiation (1 October 2010 through 28 February 2015). We used fractional polynomial regression to determine the association pattern between FOpre, FOpost and IDWG, and multivariate adjusted Cox models with FO and/or IDWG as longitudinal and time-varying predictors to determine all-cause mortality risk. In analyses using 1-month averages, patients in quartiles 3 and 4 (Q3 and Q4) of FO had an incrementally higher adjusted mortality risk compared with reference Q2, and patients in Q1 of IDWG had higher adjusted mortality compared with Q2. The highest adjusted mortality risk was observed for patients in Q4 of FOpre combined with Q1 of IDWG [hazard ratio (HR) = 2.66 (95% confidence interval 2.21-3.20), compared with FOpre-Q2/IDWG-Q2 (reference)]. Using longitudinal means of FO and IDWG only slightly altered all HRs. IDWG associated positively with FOpre, but negatively with FOpost, suggesting a link with post-dialysis extracellular volume depletion. FOpre and FOpost were consistently positive risk factors for mortality. Low IDWG was associated with short-term mortality, suggesting perhaps an effect of protein-energy wasting. FOpost reflected the volume status without IDWG, which implies that this fluid marker is clinically most intuitive and may be best suited to guide volume management in haemodialysis patients.

Relationship between shortening load, contractility, and myocardial energetics in intact dog.

PubMed

Dell'Italia, L J; Evanochko, W T; Blackwell, G G; Pearce, D J; Pohost, G M

1993-06-01

A canine model was developed to estimate left ventricular wall stress, volumes, contractility, and high-energy phosphate metabolites without the need for major surgery. A percutaneously inserted catheter-tip manometer was used to record high-fidelity left ventricular pressure while gradient echo cinemagnetic resonance (cine-MR) imaging alternated with in vivo 31P-nuclear magnetic resonance (NMR) spectroscopy during pharmacological maneuvers to increase cardiac work. Left ventricular circumferential wall stress, volumes, maximum rate of pressure development (dP/dtmax), and the ratio of phosphocreatine (PCr) to gamma-ATP (PCr/gamma-ATP) were recorded sequentially during control 1, dobutamine infusion, control 2, angiotensin infusion, and control 3 in five anesthetized, closed-chest dogs. PCr/gamma-ATP did not change significantly during controls 1-3, angiotensin, and dobutamine infusion. Left ventricular peak positive dP/dt (+dP/dtmax) increased significantly during dobutamine (3,338 +/- 831 mmHg/s, P < 0.001) but was unchanged during angiotensin (1,818 +/- 317 mmHg/s) and controls 1-3 (1,915 +/- 434 vs. 1,808 +/- 478 vs. 1,859 +/- 414 mmHg/s). However, dobutamine decreased the total systolic stress integral (area under the wall stress-time relationship) and end-diastolic and end-systolic volumes, whereas angiotensin increased these parameters compared with control conditions. The unchanged PCr/gamma-ATP is in accord with the results from other open-chest surface coil 31P-NMR experiments in the normal heart. Our assessment of left ventricular functional parameters provides new information that complements these more invasive studies in which heart rate-pressure product was measured during increases in cardiac work.(ABSTRACT TRUNCATED AT 250 WORDS)

Free-breathing whole-heart 3D cine magnetic resonance imaging with prospective respiratory motion compensation.

PubMed

Moghari, Mehdi H; Barthur, Ashita; Amaral, Maria E; Geva, Tal; Powell, Andrew J

2018-07-01

To develop and validate a new prospective respiratory motion compensation algorithm for free-breathing whole-heart 3D cine steady-state free precession (SSFP) imaging. In a 3D cine SSFP sequence, 4 excitations per cardiac cycle are re-purposed to prospectively track heart position. Specifically, their 1D image is reconstructed and routed into the scanner's standard diaphragmatic navigator processing system. If all 4 signals are in end-expiration, cine image data from the entire cardiac cycle is accepted for image reconstruction. Prospective validation was carried out in patients (N = 17) by comparing in each a conventional breath-hold 2D cine ventricular short-axis stack and a free-breathing whole-heart 3D cine data set. All 3D cine SSFP acquisitions were successful and the mean scan time was 5.9 ± 2.7 min. Left and right ventricular end-diastolic, end-systolic, and stroke volumes by 3D cine SSFP were all larger than those from 2D cine SSFP. This bias was < 6% except for right ventricular end-systolic volume that was 12%. The 3D cine images had a lower ventricular blood-to-myocardium contrast ratio, contrast-to-noise ratio, mass, and subjective quality score. The novel prospective respiratory motion compensation method for 3D cine SSFP imaging was robust and efficient and yielded slightly larger ventricular volumes and lower mass compared to breath-hold 2D cine imaging. Magn Reson Med 80:181-189, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Site-specific Microtubule-associated Protein 4 Dephosphorylation Causes Microtubule Network Densification in Pressure Overload Cardiac Hypertrophy*

PubMed Central

Chinnakkannu, Panneerselvam; Samanna, Venkatesababa; Cheng, Guangmao; Ablonczy, Zsolt; Baicu, Catalin F.; Bethard, Jennifer R.; Menick, Donald R.; Kuppuswamy, Dhandapani; Cooper, George

2010-01-01

In severe pressure overload-induced cardiac hypertrophy, a dense, stabilized microtubule network forms that interferes with cardiocyte contraction and microtubule-based transport. This is associated with persistent transcriptional up-regulation of cardiac α- and β-tubulin and microtubule-stabilizing microtubule-associated protein 4 (MAP4). There is also extensive microtubule decoration by MAP4, suggesting greater MAP4 affinity for microtubules. Because the major determinant of this affinity is site-specific MAP4 dephosphorylation, we characterized this in hypertrophied myocardium and then assessed the functional significance of each dephosphorylation site found by mimicking it in normal cardiocytes. We first isolated MAP4 from normal and pressure overload-hypertrophied feline myocardium; volume-overloaded myocardium, which has an equal degree and duration of hypertrophy but normal functional and cytoskeletal properties, served as a control for any nonspecific growth-related effects. After cloning cDNA-encoding feline MAP4 and obtaining its deduced amino acid sequence, we characterized by mass spectrometry any site-specific MAP4 dephosphorylation. Solely in pressure overload-hypertrophied myocardium, we identified striking MAP4 dephosphorylation at Ser-472 in the MAP4 N-terminal projection domain and at Ser-924 and Ser-1056 in the assembly-promoting region of the C-terminal microtubule-binding domain. Site-directed mutagenesis of MAP4 cDNA was then used to switch each serine to non-phosphorylatable alanine. Wild-type and mutated cDNAs were used to construct adenoviruses; microtubule network density, stability, and MAP4 decoration were assessed in normal cardiocytes following an equivalent level of MAP4 expression. The Ser-924 → Ala MAP4 mutant produced a microtubule phenotype indistinguishable from that seen in pressure overload hypertrophy, such that Ser-924 MAP4 dephosphorylation during pressure overload hypertrophy may be central to this cytoskeletal abnormality. PMID:20436166

Matrix modulation and heart failure: new concepts question old beliefs.

PubMed

Deschamps, Anne M; Spinale, Francis G

2005-05-01

Myocardial remodeling is a complex process involving several molecular and cellular factors. Extracellular matrix has been implicated in the remodeling process. Historically, the myocardial extracellular matrix was thought to serve solely as a means to align cells and provide structure to the tissue. Although this is one of its important functions, evidence suggests that the extracellular matrix plays a complex and divergent role in influencing cell behavior. This paper characterizes some of the notable studies on this dynamic entity and on adverse myocardial remodeling that have been published over the past year, which further question the belief that the extracellular matrix is a static structure. Progress has been made in understanding how the extracellular matrix is operative in the three major conditions (myocardial infarction, left ventricular hypertrophy due to overload, and dilated cardiomyopathy) that involve myocardial remodeling. Several studies have examined plasma profiles of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases following myocardial infarction and during left ventricular hypertrophy as surrogate markers of remodeling/remodeled myocardium. It has been demonstrated that bioactive signaling molecules and growth factors, proteases, and structural proteins influence cell-matrix interactions in the context of left ventricular hypertrophy. Finally, studies that either removed or added tissue inhibitor of metalloproteinases species in the myocardium demonstrated the importance of this regulatory protein in the remodeling process. Understanding the cellular and molecular triggers that in turn give rise to changes in the extracellular matrix could provide opportunities to modify the remodeling process.