scholarly journals Effect of Valsartan on Sarcoplasmic Reticulum Ca2+-ATPase Pump of the Left Ventricular Myocardium in Rats with Heart Failure with Preserved Ejection Fraction

2016 ◽  
Vol 1 (2) ◽  
pp. 1-9
Author(s):  
Xiao Ying ◽  
Long Weiqing ◽  
Lu Guihua ◽  
Zhang Juhong ◽  
Zhibin Huang
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Preserved Ejection Fraction ◽  
Relaxation Time Constant ◽  
Ventricular Relaxation ◽  
Constant Quantity

Objectives: The aim was to investigate the effects of valsartan on the sarcoplasmic reticulum Ca2+-ATPase pump (SERCA) and L-type Ca2+ channel current (ICaL) of the left ventricular myocardium in rats with heart failure with preserved ejection fraction. Methods: The 30-week-old male spontaneously hypertensive rats (SHRs) are randomly divided into the non-Valsartan and Valsartan groups, and the 30-week-old male Wistar-Kyoto rats served as control rats. The expression of SERCA is measured by Western blot. The ICaL is measured by whole-cell patch clamp. The left ventricular end-diastolic pressure and left ventricular relaxation time constant quantity are measured at the same time. Results: The left ventricular end-diastolic pressure is much higher in SHRs compared with that in control rats (p < 0.01). The left ventricular relaxation time constant quantity is markedly extended in SHRs compared with control rats (p < 0.01). Valsartan cannot increase the expression of SERCA nor decrease the density of ICaL compared with the non-Valsartan group (p > 0.05). Conclusions: Valsartan has no effect on SERCA and ICaL of the left ventricular myocardium in rats with heart failure with preserved ejection fraction.

scholarly journals Preload-corrected dynamic Starling mechanism in patients with heart failure with preserved ejection fraction

2018 ◽  
Vol 124 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Michinari Hieda ◽  
Erin Howden ◽  
Shigeki Shibata ◽  
Takashi Tarumi ◽  
Justin Lawley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Pressure ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Dynamic Modulation ◽  
Power Spectral ◽  
Ventricular Diastolic Dysfunction

The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume (SV) because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose of this study was to test whether the LVEDP-SV relationship remained impaired in heart failure with preserved ejection fraction (HFpEF) patients after normalization of LVEDP. Right heart catheterization and model-flow analysis of the arterial pressure waveform were performed while preload was manipulated using lower-body negative pressure to alter LVEDP. The DSM was compared at similar levels of LVEDP between HFpEF patients ( n = 10) and age-matched healthy controls ( n = 12) (HFpEF vs. controls: 10.9 ± 3.8 vs. 11.2 ± 1.3 mmHg, P = 1.00). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP vs. SV index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46 ± 0.19 vs. 0.99 ± 0.39 ml·m−2·mmHg−1, P = 0.0018). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75 ± 0.38 vs. 0.28 ± 0.26 mmHg2, P = 0.01). Conversely, the power spectral density of SV index, the output variability, was not different between the groups ( P = 0.97). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the two groups (0.71 ± 0.13 vs. 0.77 ± 0.19, P = 0.87). The DSM gain in HFpEF patients is impaired compared with age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling. NEW & NOTEWORTHY The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. Although the DSM gain is impaired in heart failure with preserved ejection fraction (HFpEF) patients, it is not clear whether this is because of higher LVEDP or left-ventricular diastolic dysfunction. The DSM gain in HFpEF patients is severely impaired, even at a similar level of LVEDP, which may reflect intrinsic left-ventricular diastolic dysfunction.

Abstract 15172: Murf1 Inhibitor Embl205 is a New Approach for Treatment of Heart Failure With Preserved Ejection Fraction in an Animal Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anett Jannasch ◽  
Antje Schauer ◽  
Virginia Kirchhoff ◽  
Runa Draskowsi ◽  
Claudia Dittfeld ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Skeletal Muscle Atrophy ◽  
Lv Function ◽  
Preserved Ejection Fraction ◽  
The Impact ◽  
Peak Gradient

Background: The novel MuRF1 inhibitor EMBL205 attenuates effectively developing skeletal muscle atrophy and dysfunction in animals with heart failure with preserved ejection fraction (HFpEF, ZSF1 rat model). The impact of EMBL205 on myocardial function in the HFpEF setting is currently unknown and was evaluated in ZSF1 rats. Methods: 20 wks-old female obese ZSF1 rats received EMBL205 (12 wks, conc. of 0.1% in chow; HFpEF-EMBL205). Age-matched untreated lean (con) and obese (HFpEF) ZSF1 rats served as controls. At 32 wks of age left ventricular (LV)-, aortic valve (AV) function and LV end diastolic pressure (LVEDP) was determined by echocardiography and invasive hemodynamic measurements. LV expression of collagen 1A (Col1A) and 3A (Col3A) was assessed by qRT-PCR, MMP2 expression was obtained by zymography and perivascular fibrosis was quantified in histological sections. Results: Development of HFpEF in ZSF1 obese animals is associated with cardiac enlargement and hypertrophy, as evident by increased myocardial weight, an increase in end diastolic volume (EDV) and LV anterior and posterior wall diameters. Diastolic LV-function is disturbed with elevation of E/é, an increased LVEDP and a preserved LV ejection fraction. AV peak velocity and peak gradient are significantly increased and AV opening area (AVA) significantly decreased. Col1A and Col3A expression are increased in HFpEF animals. EMBL205 treatment results in a significant reduction of myocardial weight and a trend towards lower EDV compared to HFpEF group. EMBL205 attenuates the increase in E/é, LVEDP, AV peak gradient and the decrease of AVA. EMBL205 significantly reduces Col3A expression and a trend for Col1A expression is seen. Increased perivascular fibrosis and MMP2 expression in HFpEF is extenuated by EMBL205 treatment (table 1). Conclusions: Application of EMBL205 attenuated the development of pathological myocardial alterations associated with HFpEF in ZSF1rats due to antifibrotic effects.

Abstract 12325: Compensatory Increase of Left Atrial External Work to Left Ventricular Dysfunction During Afterload Increase: Insights Into the Mechanism of Decompensation in Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Katsuji Inoue ◽  
Toshihiko Asanuma ◽  
Kasumi Masuda ◽  
Daisuke Sakurai ◽  
Masamichi Oka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Strain Curve ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
External Work ◽  
Reservoir Function ◽  
Left Pulmonary Vein

Introduction: Afterload mismatch is considered as a cause of acute decompensation in patients with heart failure with preserved ejection fraction (HFPEF). However, behaviors of left atrium (LA) and ventricle (LV) to afterload increase have not been fully elucidated. We investigated how LA and LV acted to acute increase in afterload using speckle tracking echocardiography. Methods: Serial echocardiographic and hemodynamic data were acquired in 10 dogs during banding of the descending aorta (AoB). LA pressure was measured by a micromanometer via left pulmonary vein. As shown in Figure, peak negative strain during LA contraction and strain change during LA relaxation (early reservoir strain) and that during systole (late reservoir strain) were generated by simultaneous acquisition of LA longitudinal strain and volume. Pressure-strain curve showed 2 loops (A-loop, V-loop) and areas in A-loop and V-loop were computed as the work during active contraction and relaxation (A-work) and that during passive filling and emptying (V-work), respectively. Results: AoB increased LV systolic pressure by about 60 mmHg, mean LA pressure (3.8±1.3 vs. 7.1±2.0 mmHg) and LV end-diastolic pressure (4.5±1.7 vs. 10.7±4.0 mmHg, all p < 0.01). LV global circumferential strain decreased (-18.8±3.5 vs. -13.2±3.5%, p < 0.01) but LV stroke volume was maintained (8.4±2.3 vs. 9.6±3.6 ml). LA peak negative strain (-2.9±2.3 vs. -9.8±4.0%, p < 0.01) and early reservoir strain (3.4±1.1 vs. 7.8±2.6%, p < 0.01) increased substantially by AoB, but late reservoir function did not change (9.3±3.5 vs. 6.1±2.0%). A-work significantly increased (3.2±2.0 to 19.2±15.1 mmHg %, p < 0.01), while V-work did not change (13.3±7.1 vs. 13.6±8.0 mmHg %). Conclusions: During aortic banding, LA contraction, early reservoir function and thereby external work during the phase increased as a compensation to LV dysfunction. The failure of this mechanism may lead to decompensation in HFPEF.

Abstract 1247: Heart Function is Transiently Sustained Despite a Near Loss of SERCA2 Protein in Cardiomyocyte-specific Serca2 null Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kristin B Andersson ◽  
Alexandra V Finsen ◽  
Ivar Sjaastad ◽  
Yibin Wang ◽  
Ju Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Clinical Signs ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Lung Weight ◽  
Adult Mice

The SERCA2 Ca 2+ ATPase is of central importance for refilling of the sarcoplasmic reticulum (SR) Ca 2+ store and cardiac contractility. Reduced SERCA2 function is associated with heart failure. We hypothesized that loss of SERCA2 would result in immediate severe myocardial contractile dysfunction and death. Transgenic mice were generated with a Cre-loxP strategy in which tamoxifen induces Serca2 ( Atp2a2 ) gene excision in the cardiomyocytes (SERCA2KO) of adult mice. In SERCA2KO mice, SERCA2 protein was rapidly reduced in left ventricular myocardium with a half-life < 3 days. After 4 weeks, SERCA2 protein was reduced to < 5% of control values. In isolated cardiomyocytes, SERCA2a, SERCA2b, SERCA1 and SERCA3 proteins were not detectable. Strikingly, SERCA2KO mice did not present clinical signs of circulatory failure at 4 weeks. Fractional shortening was preserved, and cardiac output was reduced to 80% of control values. The left atrial diameter, lung weight and left ventricular end-diastolic pressure (LVEDP) were slightly increased in SERCA2KO mice compared with controls, and the maximal rates of pressure development and decline in the left ventricle were affected with a prolongation of the ventricular relaxation time. After seven weeks, SERCA2KO mice developed severe congestive heart failure with dilated chambers, elevated LVEDP and pronounced increases in lung and atrial weights. Cardiac output was reduced to 70% of control values. There were no indications of major cardiomyocyte disarray in the myocardium at the 4 or 7 week timepoints. The abundance of Na + ,Ca 2+ exchanger, L-type Ca 2+ channel 1c and alpha2delta1 subunit proteins and Pmca1 mRNA were all increased at 4 and 7 weeks. The expression of calsequestrin protein and Ryr2 mRNA were unchanged. L-type Ca 2+ channel alpha2delta1 subunit and PMCA1 expression were further enhanced at 7 weeks in SERCA2KO mice. Thus, cardiac function is supported in SERCA2KO mice for several weeks despite the near absence of SERCA2 protein. Alterations in the expression of Ca 2+ transporting proteins suggest that Ca 2+ transients are generated over the plasma membrane rather than the SR. However, the adaptations induced by loss of SERCA2 are not sufficient for long-term support of heart function in adult mice.

Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction

2015 ◽  
Vol 309 (10) ◽  
pp. H1648-H1654 ◽  
Author(s):  
Sara Leite ◽  
Sara Rodrigues ◽  
Marta Tavares-Silva ◽  
José Oliveira-Pinto ◽  
Mohamed Alaa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Vena Cava ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Stiffness Constant ◽  
Complete Relaxation ◽  
Filling Time ◽  
Wistar Kyoto

Myocardial stiffness and upward-shifted end-diastolic pressure-volume (P-V) relationship (EDPVR) are the key to high filling pressures in heart failure with preserved ejection fraction (HFpEF). Nevertheless, many patients may remain asymptomatic unless hemodynamic stress is imposed on the myocardium. Whether delayed relaxation induced by pressure challenge may contribute to high end-diastolic pressure (EDP) remains unsettled. Our aim was to assess the effect of suddenly imposed isovolumic afterload on relaxation and EDP, exploiting a highly controlled P-V experimental evaluation setup in the ZSF1 obese rat (ZSF1 Ob) model of HFpEF. Twenty-week-old ZSF1 Ob ( n = 12), healthy Wistar-Kyoto rats (WKY, n = 11), and hypertensive ZSF1 lean control rats (ZSF1 Ln, n = 10) underwent open-thorax left ventricular (LV) P-V hemodynamic evaluation under anesthesia with sevoflurane. EDPVR was obtained by inferior vena cava occlusions to assess LV ED chamber stiffness constant β, and single-beat isovolumic afterload acquisitions were obtained by swift occlusions of the ascending aorta. ZSF1 Ob showed increased ED stiffness, delayed relaxation, as assessed by time constant of isovolumic relaxation (τ), and elevated EDP with normal ejection fraction. Isovolumic afterload increased EDP without concomitant changes in ED volume or heart rate. In isovolumic beats, relaxation was delayed to the extent that time for complete relaxation as predicted by 3.5 × monoexponentially derived τ (τexp) exceeded effective filling time. EDP elevation correlated with reduced time available to relax, which was the only independent predictor of EDP rise in multiple linear regression. Our results suggest that delayed relaxation during pressure challenge is an important contributor to lung congestion and effort intolerance in HFpEF.

Echocardiography and invasive hemodynamics during stress testing for diagnosis of heart failure with preserved ejection fraction: an experimental study

2015 ◽  
Vol 308 (12) ◽  
pp. H1556-H1563 ◽  
Author(s):  
Sara Leite ◽  
José Oliveira-Pinto ◽  
Marta Tavares-Silva ◽  
Mahmoud Abdellatif ◽  
Dulce Fontoura ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Characteristic Curve ◽  
Left Ventricular ◽  
Doppler Velocity ◽  
Preserved Ejection Fraction ◽  
Hemodynamic Stress ◽  
Effort Testing ◽  
Obese Rats

Inclusion of exercise testing in diagnostic guidelines for heart failure with preserved ejection fraction (HFpEF) has been advocated, but the target population, technical challenges, and underlying pathophysiological complexity raise difficulties to implementation. Hemodynamic stress tests may be feasible alternatives. Our aim was to test Trendelenburg positioning, phenylephrine, and dobutamine in the ZSF1 obese rat model to find echocardiographic surrogates for end-diastolic pressure (EDP) elevation and HFpEF. Seventeen-week-old Wistar-Kyoto, ZSF1 lean, and obese rats ( n = 7 each) randomly and sequentially underwent (crossover) Trendelenburg (30°), 5 μg·Kg−1·min−1 dobutamine, and 7.5 μg·Kg−1·min−1 phenylephrine with simultaneous left ventricular (LV) pressure-volume loop and echocardiography evaluation under halogenate anesthesia. Effort testing with maximum O2 consumption (V̇o2 max) determination was performed 1 wk later. Obese ZSF1 showed lower effort tolerance and V̇o2 max along with higher resting EDP. Both Trendelenburg and phenylephrine increased EDP, whereas dobutamine decreased it. Significant correlations were found between EDP and 1) peak early filling Doppler velocity of transmitral flow (E) to corresponding myocardial tissue Doppler velocity (E′) ratio, 2) E to E-wave deceleration time (E/DT) ratio, and 3) left atrial area (LAA). Diagnostic efficiency of E/DT*LAA by receiver-operating characteristic curve analysis for elevation of EDP above a cut-off of 13 mmHg during hemodynamic stress was high (area under curve, AUC = 0.95) but not higher than that of E/E′ (AUC = 0.77, P = 0.15). Results in ZSF1 obese rats suggest that noninvasive echocardiography after hemodynamic stress induced by phenylephrine or Trendelenburg can enhance diagnosis of stable HFpEF and constitute an alternative to effort testing.

scholarly journals Wedge Pressure Rather Than Left Ventricular End-Diastolic Pressure Predicts Outcome in Heart Failure With Preserved Ejection Fraction

2017 ◽  
Vol 5 (11) ◽  
pp. 795-801 ◽  
Author(s):  
Julia Mascherbauer ◽  
Caroline Zotter-Tufaro ◽  
Franz Duca ◽  
Christina Binder ◽  
Matthias Koschutnik ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Wedge Pressure

scholarly journals A study of association between heart failure with preserved ejection fraction with hypertension and diabetes mellitus

2021 ◽  
Vol 12 (12) ◽  
pp. 58-61
Author(s):  
Swapan Sarkar ◽  
Joydeep Biswas ◽  
Suprotim Ghosh
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Strong Association ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

Background: Heart failure is a common clinical entity which we come across in our daily practice and accounts for significant mortality and morbidity. The basic pathophysiology lies in the inability of the heart to pump adequate blood (output) to meet the demands of circulation/tissue or can do so only at the expense of elevated left ventricular filling pressure. Among various types of heart failure, heart failure with preserved ejection fraction (HFpEF) is still a poorly understood entity and several comorbidities such as hypertension, diabetes, coronary artery disease, obesity, and CKD are common association of HFpEF. Diabetes causes heart failure by increasing the risk of CAD and by direct injury to myocardium (cardiomyopathy). Hence, in this cross-sectional observational study, we assess the cardiovascular risk factors such as hypertension and diabetes mellitus in association with HFpEF. Aims and Objectives: This study aims to establish the hypothesis that hypertension and diabetes mellitus are associated with a predictor of HFpEF. Materials and Methods: Ninety patients were selected. NTproBNP, HbA1C, FBS, PPBS level, and blood pressure was measured and echocardiogram was performed to assess ratio of transmitral flow velocity and annular velocity (E/E’); left ventricular end-diastolic pressure; and left ventricular ejection fraction (LVEF). Results: The mean age was 64±7. Forty-two (46.67%) were men and 48 (53.33%) were female. Hypertension was present in 73 (81.11%) and diabetes in 44 (48.89%). E/E´, a parameter of LV diastolic function, showed positive correlation to both risk factors in study (r=0.653, p<0.001). Linear regression indicated that E/E’ (β-coefficient=0.845, p<0.001) was significantly associated with the presence of risk factors. Conclusion: The data show that the prevalence of HTN and DM is significantly higher in patients with HFpEF and establishes a strong association between duration of HTN and DM with symptomatic HFpEF.

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