Left ventricular shape changes during the course of evolving heart failure

The temporal relationship between left ventricular (LV) shape changes and the development of LV dysfunction, dilation, and sympathoadrenergic hyperactivity was examined in 10 dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. LV shape was quantitated from serial ventriculograms based on the ratio of the major to minor axis at end systole and end diastole. Measurements were made at baseline (before embolizations) and were repeated at 2, 8, and 16 wk after the last embolization. A significant increase of LV sphericity was present at 2 wk, with only minimal changes occurring thereafter. Despite the tendency for LV shape changes to plateau between 2 and 16 wk, LV ejection fraction continued to decline (31 +/- 1 vs. 20 +/- 2%; P less than 0.001), and LV end-diastolic volume continued to increase (86 +/- 6 vs. 103 +/- 9 ml; P less than 0.01) as did plasma norepinephrine concentration (456 +/- 30 vs. 868 +/- 172 pg/ml; P less than 0.02). These data indicate that in the course of evolving heart failure, LV shape abnormalities precede the development of profound LV dysfunction, dilation, and overt activation of the sympathetic nervous system.

Download Full-text

A canine model of chronic heart failure produced by multiple sequential coronary microembolizations

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.4.h1379 ◽

1991 ◽

Vol 260 (4) ◽

pp. H1379-H1384 ◽

Cited By ~ 40

Author(s):

H. N. Sabbah ◽

P. D. Stein ◽

T. Kono ◽

M. Gheorghiade ◽

T. B. Levine ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Diastolic Pressure ◽

Plasma Renin ◽

Canine Model ◽

Left Ventricular ◽

Plasma Norepinephrine ◽

End Diastolic Volume ◽

Lv Ejection Fraction

A canine model of chronic heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Twenty closed-chest dogs underwent three to nine intracoronary embolizations performed 1-3 wk apart. Embolizations were discontinued when left ventricular (LV) ejection fraction was less than 35%. LV ejection fraction was 64 +/- 2% at baseline and decreased to 21 +/- 1% at 3 mo after the last embolization (P less than 0.001). During the same period, LV end-diastolic pressure increased from 6 +/- 1 to 22 +/- 3 mmHg (P less than 0.001); LV end-diastolic volume increased from 64 +/- 3 to 101 +/- 6 6 ml (P less than 0.001), and cardiac output decreased from 2.9 +/- 0.2 to 2.3 +/- 0.1 l/min (P less than 0.01). These changes were accompanied by significant increases of pulmonary artery wedge pressure and systemic vascular resistance. Plasma norepinephrine increased from 332 +/- 17 pg/ml at baseline to 791 +/- 131 pg/ml at 3 mo after the last embolization (P less than 0.01); plasma levels of atrial natriuretic factor increased from 12.7 +/- 10.0 to 28.8 +/- 8.6 pmol/l (P less than 0.01), whereas plasma renin activity remained unchanged. Gross and microscopic postmortem examination showed patchy myocardial fibrosis and LV hypertrophy. We conclude that multiple intracoronary embolizations with microspheres, separated in time, can lead to chronic heart failure in dogs. The preparation is stable and reproducible and manifests many of the sequelae of heart failure that result from loss of contractile myocardium.

Download Full-text

Effect of chronic left ventricular failure on beta-endorphin

Journal of Applied Physiology ◽

10.1152/jappl.1992.73.6.2675 ◽

1992 ◽

Vol 73 (6) ◽

pp. 2675-2680 ◽

Cited By ~ 1

Author(s):

E. Mellow ◽

E. Redei ◽

K. Marzo ◽

J. R. Wilson

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Chronic Heart Failure ◽

Left Ventricular ◽

Plasma Norepinephrine ◽

Endogenous Opiates ◽

Beta Endorphin ◽

Arterial Blood ◽

Norepinephrine Concentration ◽

C 30

Stimulation of endogenous opiate secretion worsens circulatory dysfunction in several forms of shock, in part by inhibiting sympathetic activity. To investigate whether endogenous opiates have a similar effect in chronic heart failure (HF), we measured beta-endorphin concentrations and hemodynamic responses to naloxone infusion (2 mg/kg bolus + 2 mg.kg-1 x h-1) in six control (C) dogs and eight dogs with low-output HF produced by 3 wk of rapid ventricular pacing. The dogs with HF exhibited reduced arterial blood pressure (C, 123 +/- 4 vs. HF, 85 +/- 7 mmHg; P < 0.01) and cardiac outputs (C, 179 +/- 14 vs. HF, 76 +/- 2 ml.min-1 x kg-1; P < 0.01) and elevated plasma norepinephrine concentrations (C, 99 +/- 12 vs. HF, 996 +/- 178 pg/ml; P < 0.01) but normal beta-endorphin concentrations (C, 30 +/- 11 vs. HF, 34 +/- 12 pg/ml; P = NS). Naloxone produced similar transitory increases in blood pressure (C, 14 +/- 5 vs. HF, 26 +/- 25%) and cardiac output (C, 37 +/- 13 vs. HF, 22 +/- 15%) in both groups (both P = NS). No significant changes in norepinephrine concentration or systemic vascular resistance were observed in either group. These findings suggest that beta-endorphin secretion does not exacerbate circulatory dysfunction in chronic heart failure.

Download Full-text

Atrial natriuretic peptide and sodium homeostasis in compensated heart failure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.271.5.r1353 ◽

1996 ◽

Vol 271 (5) ◽

pp. R1353-R1363 ◽

Cited By ~ 2

Author(s):

T. E. Lohmeier ◽

H. L. Mizelle ◽

G. A. Reinhart ◽

J. P. Montani ◽

C. E. Hord ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Output ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Plasma Levels ◽

Left Ventricular ◽

Sodium Balance ◽

Plasma Norepinephrine ◽

Norepinephrine Concentration ◽

Atrial Natriuretic

The purpose of this study was to determine whether high plasma levels of atrial natriuretic peptide (ANP) in compensated heart failure are important in the maintenance of sodium balance. This was achieved by subjecting eight dogs to bilateral atrial appendectomy (APX) to blunt the ANP response to pacing-induced heart failure. Five intact dogs served as controls. In controls, 14 days of left ventricular pacing at 240 beats/min produced a sustained fall in cardiac output and mean arterial pressure of approximately 40 and 20%, respectively; compared with cardiac output, reductions in renal blood flow (up to approximately 25%) were less pronounced and even smaller decrements in GFR occurred (up to 9%). Despite these changes and a threefold elevation in plasma norepinephrine concentration, plasma renin activity (PRA) did not increase and sodium balance was achieved during the second week of pacing in association with a six- to eightfold rise in plasma levels of ANP. Similar responses occurred in four dogs in which APX was relatively ineffective in blunting the ANP response to pacing. In marked contrast, there were substantial increments in PRA and in plasma norepinephrine concentration, and marked sodium and water retention during the last week of pacing in four dogs with APX and severely deficient ANP. These results indicate that ANP plays a critical role in promoting sodium excretion in the early stages of cardiac dysfunction.

Download Full-text

SR Ca(2+)-ATPase activity and expression in ventricular myocardium of dogs with heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.1.h12 ◽

1997 ◽

Vol 273 (1) ◽

pp. H12-H18 ◽

Cited By ~ 7

Author(s):

R. C. Gupta ◽

H. Shimoyama ◽

M. Tanimura ◽

R. Nair ◽

M. Lesch ◽

...

Keyword(s):

Heart Failure ◽

Atpase Activity ◽

Sodium Dodecyl ◽

Ventricular Myocardium ◽

Left Ventricular ◽

Maximal Velocity ◽

Protein Levels ◽

Lv Dysfunction ◽

Lv Ejection Fraction ◽

Tissue Specimens

The purpose of this study was to examine the activity and expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase in left ventricular (LV) myocardium of dogs with chronic heart failure (HF). LV and right ventricular (RV) tissue specimens were obtained from six normal (NL) control dogs and six dogs with chronic HF (LV ejection fraction, 23 +/- 2%) produced by multiple sequential intracoronary microembolizations. Thapsigargin-sensitive Ca(2+)-ATPase activity was measured in isolated SR membrane fractions prepared from LV and RV myocardium. Ca(2+)-ATPase expression, using a specific dog myocardium monoclonal antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV and RV myocardium. Ca(2+)-ATPase activity in both ventricles of NL or HF dogs increased with increasing Ca2+ concentration and reached a plateau at 3 microM Ca2+. The maximal velocity (Vmax, mumol Pi released.min-1.mg-1) of Ca(2+)-ATPase activity was significantly lower in LV of HF dogs compared with NL (0.15 +/- 0.01 vs. 0.23 +/- 0.01, P < 0.05), whereas the affinity of the Ca2+ pump for Ca2+ was unchanged. LV tissue levels of Ca(2+)-ATPase (densitometric units/5 micrograms noncollagen protein) were also significantly lower in LV myocardium of HF dogs compared with NL (3.52 +/- 0.43 vs. 5.53 +/- 0.47, P < 0.05). No significant differences in Ca(2+)-ATPase activity or expression were observed in RV myocardium of HF dogs compared with NL. We conclude that SR Ca(2+)-ATPase activity and protein levels are reduced in LV myocardium of dogs with chronic HF. This abnormality of the SR Ca2+ pump of the failed LV can result in impaired Ca2+ uptake and ultimately to Ca2+ overload and global LV dysfunction.

Download Full-text

Effects of AT1-receptor blockade on progression of left ventricular dysfunction in dogs with heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.4.h1385 ◽

1999 ◽

Vol 276 (4) ◽

pp. H1385-H1392 ◽

Cited By ~ 7

Author(s):

Mitsuhiro Tanimura ◽

Victor G. Sharov ◽

Hisashi Shimoyama ◽

Takayuki Mishima ◽

T. Barry Levine ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Low Dose ◽

Left Ventricular ◽

Term Therapy ◽

High Dose ◽

Lv Dysfunction ◽

Lv Ejection Fraction

The objective of the present study was to determine the effects of early long-term monotherapy with the angiotensin II AT1-receptor antagonist valsartan on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure (HF). Studies were performed in 30 dogs with moderate HF produced by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LV ejection fraction was 30–40%. Two weeks after the last embolization, dogs were randomized to 3 mo of oral therapy with low-dose valsartan (400 mg twice daily, n = 10), to high-dose valsartan (800 mg twice daily, n = 10), or to no treatment at all (control, n = 10). Treatment with valsartan significantly reduced mean aortic pressure and LV end-diastolic pressure compared with control. In untreated dogs, LV ejection fraction decreased (37 ± 1 vs. 29 ± 1%, P = 0.001) and end-systolic volume (ESV) and end-diastolic volume (EDV) increased (81 ± 5 vs. 92 ± 5 ml, P < 0.001; 51 ± 3 vs. 65 ± 3 ml, P = 0.001, respectively) after 3 mo of follow-up compared with those levels before follow-up. In dogs treated for 3 mo with low-dose valsartan, ejection fraction was preserved (37 ± 1 vs. 38 ± 2%, pretreatment vs. posttreatment) as was ESV but not EDV. In dogs treated for 3 mo with high-dose valsartan, ejection fraction decreased (35 ± 1 vs. 31 ± 2%, P = 0.02) and ESV and EDV increased in a manner comparable to those levels in controls. Valsartan had no significant effects on cardiomyocyte hypertrophy or on the extent of interstitial fibrosis. We conclude that, for dogs with moderate HF, early long-term therapy with the AT1-receptor blocker valsartan decreases preload and afterload but has only limited benefits in attenuating the progression of LV dysfunction and chamber remodeling.

Download Full-text

Endogenous β3-adrenoreceptor activation contributes to left ventricular and cardiomyocyte dysfunction in heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01045.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. H2425-H2433 ◽

Cited By ~ 51

Author(s):

Atsushi Morimoto ◽

Hiroshi Hasegawa ◽

Heng-Jie Cheng ◽

William C. Little ◽

Che-Ping Cheng

Keyword(s):

Heart Failure ◽

Left Ventricular ◽

Cardiac Contraction ◽

Plasma Norepinephrine ◽

Endogenous Catecholamine ◽

Norepinephrine Concentration ◽

Before And After ◽

Intracellular Ca ◽

Volume Relation ◽

Stimulation Of

The objective of the present study was to test the hypothesis that endogenous β3-adrenoreceptor (AR) activation contributes to left ventricular (LV) and cardiomyocyte dysfunction in heart failure (CHF). Stimulation of the β3-AR inhibits cardiac contraction. In the failing myocardium, β3-ARs are upregulated, suggesting that stimulation of β3-ARs may contribute to depressed cardiac performance in CHF. We assessed the functional significance of endogenous β3-AR activation in 10 conscious dogs before and after pacing-induced CHF. Under normal conditions, L-748,337, a specific β3-AR antagonist, produced a mild increase in LV contractile performance assessed by the slope ( Ees) of the LV pressure-volume relation (18%, 6.2 ± 0.9 vs. 7.3 ± 1.2 mmHg/ml, P < 0.05) and the improved LV relaxation time constant (τ; 28.4 ± 1.9 vs. 26.8 ± 1.0 ms, P < 0.05). After CHF, the plasma norepinephrine concentration increased eightfold, and L-748,337 produced a larger increase in Ees (34%, 3.8 ± 0.7 vs. 5.1 ± 0.8 mmHg/ml, P < 0.05) and a greater decrease in τ (46.4 ± 4.2 vs. 41.0 ± 3.9 ms, P < 0.05). Similar responses were observed in isolated myocytes harvested from LV biopsies before and after CHF. In the normal myocyte, L-748,337 did not cause significant changes in contraction or relengthening. In contrast, in CHF myocytes, L-748,337 produced significant increases in contraction (5.8 ± 0.9 vs. 6.8 ± 0.9%, P < 0.05) and relengthening (33.5 ± 4.2 vs. 39.7 ± 4.0 μm/s, P < 0.05). The L-748,337-induced myocyte response was associated with improved intracellular Ca2+ concentration regulation. In CHF myocytes, nadolol caused a decrease in contraction and relengthening, and adding isoproterenol to nadolol caused a further depression of myocyte function. Stimulation of β3-AR by endogenous catecholamine contributes to the depression of LV contraction and relaxation in CHF.

Download Full-text

Heart failure grading using single-lead electrocardiography

10.1101/2020.10.08.20209700 ◽

2020 ◽

Author(s):

Eriko Hasumi ◽

Katsuhito Fujiu ◽

Ying Chen ◽

Yu Shimizu ◽

Tsukasa Oshima ◽

...

Keyword(s):

Heart Failure ◽

Early Detection ◽

Operating Characteristic ◽

Characteristic Curve ◽

Left Ventricular ◽

Healthy Controls ◽

Lv Dysfunction ◽

Operating Characteristic Curve ◽

Lv Ejection Fraction ◽

Ecg Data

AbstractConvolutional neural networks (CNNs) applied to electrocardiograms (ECGs) have been showing utility for detecting left ventricular (LV) dysfunction1. Although early detection of reduced LV ejection fraction (rEF) could improve handling of heart failure (HF) with rEF (HFrEF), it is not sufficient to detect HF with preserved EF (HFpEF). Here we developed a CNN algorithm to classify the severity of HF based on single-lead ECG data, irrespective of EF. We trained a CNN using ECG data and the HF classification from 7,865 patients with HF. The CNN achieved an area under the receiver-operating characteristic curve (AUC) of 0.996 for distinguishing patients with HF of various severity from healthy controls. It is anticipated that early detection of HF and therapeutic management of HF patients can be improved by employing this CNN with a single-lead ECG device.

Download Full-text

Chronic heart failure induced by coronary artery ligation in Lewis inbred rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.2.h722 ◽

1997 ◽

Vol 272 (2) ◽

pp. H722-H727 ◽

Cited By ~ 25

Author(s):

Y. H. Liu ◽

X. P. Yang ◽

O. Nass ◽

H. N. Sabbah ◽

E. Peterson ◽

...

Keyword(s):

Heart Failure ◽

Coronary Artery ◽

Cardiac Dysfunction ◽

Left Ventricular ◽

Coronary Artery Ligation ◽

Sprague Dawley ◽

End Diastolic Volume ◽

Lv Dysfunction ◽

Sprague Dawley Rats ◽

Inbred Rats

Rat models of heart failure (HF) secondary to myocardial infarction (MI) are useful in studying the progression of cardiac dysfunction and in testing therapeutic approaches. Sprague-Dawley rats are frequently used; however, this model is hampered by high mortality and a marked variability in infarct size and cardiac dysfunction, necessitating large numbers of rats and prolonged follow-up when studying the progression of dysfunction. In the present work, we developed a model of HF utilizing Lewis inbred rats. Ligation of the left anterior descending coronary artery in Lewis rats produced more uniform and larger infarcts (40 +/- 1.7 vs. 28 +/- 2.3%; P < 0.001) and lower mortality (16 vs. 36%; P < 0.001) than in Sprague-Dawley rats. Using this rat model, we further studied the course of left ventricular (LV) dysfunction and enlargement from 1 wk to 6 mo after MI with cineventriculography. LV end-systolic volume and end-diastolic volume were determined with the area-length method. LV ejection fraction ranged between 0.57 and 0.62 in control rats; after MI, it decreased significantly to 0.48 +/- 0.04 at 1 wk, 0.36 +/- 0.02 at 2 wk, 0.48 +/- 0.02 at 1 mo, 0.35 +/- 0.03 at 2 mo, 0.30 +/- 0.02 at 3 mo, 0.31 +/- 0.02 at 4 mo, and 0.24 +/- 0.02 at 6 mo (P < 0.001, MI vs. sham). LV end-diastolic volume in control rats ranged between 0.32 and 0.42 ml; it increased to 0.48 +/- 0.04 ml at 1 wk, 0.46 +/- 0.02 ml at 2 wk, and 0.46 +/- 0.03 ml at 1 mo. It markedly increased to 0.79 +/- 0.03, 0.79 +/- 0.06, 0.78 +/- 0.03, and 0.80 +/- 0.05 ml at 2, 3, 4, and 6 mo, respectively, after MI (P < 0.001 vs. sham). LV end-diastolic pressure was significantly elevated at all time points. Thus coronary ligation in Lewis inbred rats produces uniformly large infarcts with low mortality, progressive LV dysfunction, and increased LV chamber size. This model may be useful in studying chronic HF secondary to MI.

Download Full-text

A Systematic Review and Meta-analysis : Safety and Efficacy of Mesenchymal stem Cells Therapy for Heart Failure

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15999200820171432 ◽

2020 ◽

Vol 15 ◽

Author(s):

Tiantian Shen ◽

Lin Xia ◽

Wenliang Dong ◽

Jiaxue Wang ◽

Feng Su ◽

...

Keyword(s):

Heart Failure ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Safety And Efficacy ◽

Systolic Volume ◽

End Diastolic Volume ◽

End Systolic Volume

Background: Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating heart failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. Methods: We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized controlled trials(RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model when it appropriate by use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by death and rehospitalization and the secondary outcome was efficacy which was assessed by six-minute walk distance and left ventricular ejection fraction (LVEF)，left ventricular end-systolic volume（LVESV），left ventricular end-diastolic volume（LVEDV） and brain natriuretic peptide（BNP） Results: A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT.MSCs transplantation significantly improved left ventricular ejection fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased left ventricular end-systolic volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, -12.83], p<0.00001 ) and left ventricular end-diastolic volume (LVEDV) by 5.78 ml (MD [95% CI]=-5.78[-12.00, 0.43], p=0.07 ) ,in the MSCs group , BNP was decreased by 133.51 pg/ml MD [95% CI]= -133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. Conclusions: Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure is safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.

Download Full-text