Experimental Models Of Heart Failure Research Articles

Morphometric analysis of atrial natriuretic peptide-containing granules in atriocytes of rats with experimental congestive heart failure

The morphometric characteristics of atrial natriuretic peptide-containing granules were studied in atrial myoendocrine cells of rats with aorto-caval fistula, an experimental model of congestive heart failure. A total of 6680 granules of control and aorto-caval rats were analyzed by a computerized image analysis system that evaluated the number and sectioned surface area of granules and their subcellular location. Compared with control animals, rats with congestive heart failure displayed a slight increase in the number of peripheral granules, adjacent to the sarcolemma, but not centrally located in the Golgi areas. The mean sectioned surface area of granules in rats with congestive heart failure was about 50% of that in controls, both in the right and left atria. Rats with aorto-caval fistula had a higher percent of small granules and lower percent of large granules compared with controls. The data demonstrate different morphometric characteristics in atrial natriuretic peptide-containing granules in atriocytes in rats with experimental congestive heart failure; this may reflect the enhanced synthesis and release of atrial natriuretic peptide in heart failure.

948-49 Prognostic Importance of the Oxidation Products of Catecholamines (Adrenochromes) in Patients with Heart Failure

In experimental models of heart failure (HF) free-radical formation has been shown to be increased and considered to be involved in pathophysiologic mechanisms leading to progressive ventricular dysfunction. Adrenochromes, the products of oxidation of norepinephrine (NE) are thought to reflect oxidative stress (amount of free-radical formation) and to be more cytotoxic than NE. To investigate the importance of adrenochromes in HF, we measured adrenolutins (AL), stable breakdown products of adrenochromes, along with plasma NE, and N-terminal atrial natriuretic factor (ANFI) in 257 patients at baseline entering the PROFILE study of flosequinan. We then related these variables to mortality (21 — progressive HF, 27 — sudden cardiac deaths and 9 - other causes) over a 20-month period. ANF LVEF (pmo/l) NE (pg/ml) AL (ng/ml) Age (yrs) (%) Alive (200) 2739 406 43 65 23 Dead (57) 3121 503 * 80 * 65 20 * * P < 0.05 Alive versus Dead In a multivariant model including these variables, as well as NYHA class, gender, and treatment groups (flosequinan or placebo), AL was the most significant predictor of death (P = 0.005). In patients dying with progressive HF or of other causes, AL was a better predictor of death than NE, while in patients dying of a sudden cardiac death, NE was a better predictor. Thus, measurement of AL appears to be a new prognostic factor in patients with HF. These results suggest a role for free-radical formation in the pathophysiologyof HF and provide a new opportunity for therapy.

1031-38 Beneficial Effects of Ramipril in a Model of Isoproterenol-induced Heart Failure in the Rat

To establish an experimental model of chronic heart failure, we assessed the morphologic, hemodynamic and neurohumoral effects of a single large dose for isoproterenol (ISO: 150 mg/kg BW s.c.). Two weeks after ISO-application 45 ISO- and 30 control-rats were examined. In addition, we investigated the effects of chronic treatment with ramipril (RAM: 10 mg/KG/d, n = 20). Echocardiography of ISO- and control-rats was performed in anesthetized rats to measure left ventricular (LV) mass and LV-enddiastolic dimension. An increase of LV-mass (LV diastolic posterior wall thickness: 2.8 ± 0.2 vs. 1.9 ± 0.3 mm, LV systolic posterior wall thickness: 4.3 ± 0.4 vs. 3.6 ± 0.3 mm; p < 0.01) and LV enddiastolic dimension (6.9 ± 0.6 vs. 4.9 ± 0.3 mm p < 0.01) was displayed. RAM-treated animals showed a highly significant decrease of LV mass and LV-enddiastolic dimension (p < 0.001). Heart rate was increased in the ISO-group (p < 0.005) compared to RAM- and control-rats (p < 0.005). Central venous pressure was significantly increased in the ISO-group (5.8 ± 2.3; vs 2.3 ± 0.6 mmHG; p < 0.01) and decreased to normal ranges in RAMrats. Mean arterial pressure was decreased in ISO- (121.3 ± 14.8 mmHg) and RAM-rats, (95 ± 3 mmHG) vs controls (132.4 ± 19.5 mmHG)(p < 0.05). Mean renal blood flow between ISO-treated and control group was not significantly different, in contrast the mean blood flow in the abdominal aorta was decreased in the ISO-group (p < 0.05). Cardiac ACE-activity (p < 0.01), circulating atrial natriuretic peptide, renin- and aldosterone-levels were significantly higher in the ISO-treated group as compared tothe control group (p < 0.05). ISO-treated hearts displayed morphological alterations such as myocyte necrosis, cellular reaction and fibrosis. RAM-treated hearts revealed the same infarct-like lesions but at a lower grade. In summary, a highly reproducible model of chronic heart failure was established. Hemodynamic measurements displayed a typical characteristic for advanced heart failure in the ISO-group. Blockade of the renin-angiotensinsystem (RAS) attenuated the observed changes indicating that the RAS may be involved in the development of catecholamine-induced congestive heart failure.

Dopaminergic agonists: Efficacy in an experimental model of heart failure

Dopaminergic agonists: Efficacy in an experimental model of heart failure

S33-4 - Actions of a nonpeptide vasopressin V1 receptor antagonist on experimental heart failure models

S33-4 - Actions of a nonpeptide vasopressin V1 receptor antagonist on experimental heart failure models

P1-114 - Involvement of phorbol ester-sensitive signal transduction in the impaired relaxation of rat aorta to acetylcholine in the experimental heart failure model

P1-114 - Involvement of phorbol ester-sensitive signal transduction in the impaired relaxation of rat aorta to acetylcholine in the experimental heart failure model

Effect of cardiomyoplasty on systolic and diastolic function

Although cardiomyoplasty has become a recognized treatment for end-stage heart failure, the effects of this procedure on systolic and diastolic function are still unclear. To determine the effects of paced and non-paced latissimus dorsi cardiomyoplasty on systolic and diastolic function, the maximal elastance of the left ventricle (Emax), stroke volume, preload recruitable stroke work and diastolic compliance were measured in an experimental heart failure model. Collateral blood vessels to the latissimus dorsi were ligated 2 weeks before cardiomyoplasty in order to reduce the risk of ischemic injury. Histological examination of muscle biopsies confirmed that the two-stage procedure preserved normal muscle architecture. The non-paced cardiomyoplasty wrap adversely affected both systolic and diastolic function. Paced Latissimus Dorsi during heart failure improved systolic function but had no measurable effect on diastolic function. 1. Non-paced, or unstimulated, latissimus dorsi cardiomyoplasty acutely impairs cardiac function. 2. Delayed cardiomyoplasty, 2 weeks after collateral ligation, prevents ischemic injury to the muscle flap.

Angiotensin II receptor subtypes: selective antagonists and functional correlates.

Angiotensin II (Ang II) receptor heterogeneity is currently defined by the new subtype-selective agents, losartan (AT1) and PD123177 (AT2). Although both subtypes have been cloned and sequenced, only the AT1 receptor has been shown to have an important physiological or pathophysiological role. AT1 and AT2 receptors are found in both normal and failing cardiac tissue. They are found on myocytes, endothelial cells, fibroblasts, coronary arterial smooth muscle cells, and peripheral sympathetic nerves. The AT1 receptors mediate virtually all of the effects of Ang II in myocytes even though cardiac tissue may contain over 50% AT2 sites. In endothelial cells, functional responses are predominately AT1. In fibroblasts, preliminary data suggest that AT2 receptors may be involved in collagen synthesis. In isolated tissue, Ang II has a limited positive inotropic effect in atrial, but not in ventricular tissue, which is blocked by losartan. Ang II may also have a tonic effect on coronary artery resistance as angiotensin inhibitors can increase coronary flow. Both ACE (Ang II synthesis) inhibitors and Ang II receptor antagonists produce beneficial effects in experimental models of heart failure, suggesting Ang II is an important mediator of heart failure. Because ACE inhibitors also potentiate bradykinin and are non-specific inhibitors of Ang II synthesis (availability of Ang II to both receptor subtypes) some differences can be anticipated. At the present time, however, the beneficial role of bradykinin is controversial and the predominant functional Ang II receptor in the heart and other tissues is the AT1 subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oral AVP receptor antagonists OPC-21268 and OPC-31260 on congestive heart failure in conscious dogs

Rapid right ventricular pacing could induce congestive heart failure in conscious dogs with significant increase in plasma concentration of arginine vasopressin (AVP) (from 1.2 +/- 0.2 to 3.4 +/- 0.6 pg/ml). In this experimental model of heart failure, oral administration of the selective AVP V1 receptor antagonist OPC-21268 significantly increased cardiac output and improved renal function without significant changes in serum electrolytes and hormones. Oral administration of the selective AVP V2 receptor antagonist OPC-31260 induced marked water diuresis, which resulted in significant increases in serum sodium concentration, plasma renin activity, and plasma concentration of AVP, although it did not produce hemodynamic improvement. Combined administration of OPC-21268 and OPC-31260 showed supra-additive hemodynamic responses as well as additive renal and metabolic responses, i.e., it showed prolonged decrease in mean arterial pressure and profound increase in cardiac output. These results suggest that AVP plays a significant role in elevation of vascular tone through V1 receptors and plays a major role in retaining free water through V2 receptors in this model of heart failure. Furthermore, combined administration of V1 and V2 receptor antagonists could induce not only metabolic and hormonal responses but also more beneficial hemodynamic responses than those observed following treatment with V1 receptor antagonist alone.

Compensatory and maladaptive responses to cardiac dysfunction

The past few years have witnessed an extraordinary number of important developments in the study of compensatory and maladaptive responses to cardiac dysfunction. It now seems clear that the process whereby the heart remodels in response to left ventricular injury is of paramount importance in the expression of clinical heart failure. There have been parallel attempts by basic scientists and clinical investigators to understand better the fundamental biologic processes that underlie remodeling and to assess numerous new treatments--especially angiotensin-converting enzyme inhibitors. A general consensus seems to be emerging that holds that the response of the heart to acute injury includes a number of highly compensatory and adaptive mechanisms that ultimately become maladaptive and contribute to cardiomegaly and severe congestive heart failure. Such mechanisms undoubtedly include local and systemic release of cytokines, peptides, and neurohormones, and altered loading conditions leading to unusual mechanical forces on cardiac myocytes and other cells of the heart. At the organ level there is hypertrophy, dilatation and growth of the interstitium. Preliminary evidence also suggests there may be some "remodeling" at the cardiac myocyte level. Reduction in peripheral vasodilator reserve is seen in experimental animal models of heart failure. Patients with heart failure also develop an endothelial-dependent form of peripheral vascular dysfunction expressed clinically as an attenuated ability to dilate in response to such stimuli as acetylcholine. The transition point whereby these myocardial and peripheral vascular abnormalities become clearly dysfunctional and contribute toward the full clinical expression of heart failure remains to be further investigated.

The Effects of Dobutamine, Propranolol and Nitroglycerin on an Experimental Canine Model of Congestive Heart Failure

The Effects of Dobutamine, Propranolol and Nitroglycerin on an Experimental Canine Model of Congestive Heart Failure

Dual natriuretic peptide system in experimental heart failure

Objectives. The objectives of this study were 1) to define in an experimental model of heart failure the time course of changes in plasma brain natriuretic peptide concentrations during the development of and recovery from heart failure, and 2) to relate these changes to changes in atrial natriuretic peptide concentration and hemodynamic status.Background. Brain natriuretic peptide is a circulating peptide with homology to atrial natriuretic peptide. However, unlike the latter, its changes during heart failure and its relation to cardiac filling pressures have not been studied.Methods. Eight male mongrel dogs underwent right ventricular pacing at 250 beats/min for 3 weeks until heart failure occurred and were followed up during recovery for 4 weeks after cessation of pacing.Results. Heart failure was characterized by an increase in both left ventricular end-diastolic pressure (6.6 ± 4.1 mm Hg at the control measurements to 35.1 ± 5.9 mm Hg at 3 weeks, p < 0.01) and right atrial pressure (6.7 ± 1.1 to 11.4 ± 2.1 mm Hg, p < 0.01). Recovery was accompanied by a return of cardiac filling pressures to control level. The time course of change of arterial plasma brain natriuretic peptide concentration was similar to that of atrial natriuretic peptide. Plasma concentrations of both peptides increased after 1 week of pacing (16 ± 4 pg/ml at the control measurement to 59 ± 20 pg/ml at 1 week, p < 0.001 for brain natriuretic peptide and 84 ± 55 to 856 ± 295 pg/ml, p < 0.001 for atrial natriuretic peptide). The level of both peptides then stayed level with no further increase at 3 weeks and returned to the control value by 4 weeks of recovery. There was an excellent correlation between plasma concentrations of the two peptides (r = 0.86, p < 0.001) and between the two peptides and cardiac filling pressures. However, compared with atrial natriuretic peptide, plasma brain natriuretic peptide concentration had a smaller percent increase during evolving heart failure and a slower rate of decline at recovery.Conclusions. Brain and atrial natriuretic peptide constitute a dual natriuretic system and are both responsive to changes in cardiac filling pressures in heart failure. However, brain natriuretic peptide appears to be less responsive than atrial natriuretic peptide.

Low-dose atrial natriuretic factor and furosemide in experimental acute congestive heart failure.

This study was designed to address three objectives in an experimental model of acute congestive heart failure (CHF) in the dog produced by rapid ventricular pacing. The first objective was to characterize cardiorenal and humoral responses before and during 2 h of acute CHF. The second objective was to determine the modulating action of iv furosemide upon these biologic responses to acute CHF, testing the hypothesis that furosemide-mediated natriuresis is associated with activation of the renin-angiotensin-aldosterone system (RAAS) compared with the control group. The third objective was to determine the modulating action of continuous low-dose atrial natriuretic factor (ANF) administration during acute CHF upon these biologic responses, testing the hypothesis that exogenous low-dose ANF would prevent activation of the RAAS and enhance the natriuretic action of furosemide. In the control group (Group 1; N = 6), plasma ANF increased after the onset of CHF; GFR and sodium excretion were maintained without activation of this RAAS despite arterial hypotension. In Group 2 (N = 6), furosemide in acute CHF increased sodium excretion but in association with a decrease in GFR and activation of the RAAS. Low-dose exogenous ANF and furosemide (Group 3; N = 6) in acute CHF were associated with a maintenance of GFR, no activation of the RAAS, and potentiation of furosemide-induced natriuresis. In summary, these studies demonstrate that furosemide potently increases sodium excretion in acute CHF, but with a decrease in GFR and activation of the RAAS. Low-dose ANF in acute CHF with furosemide maintains GFR, attenuates activation of the RAAS, and potentiates natriuresis.

Regulation of renal glomerular and papillary ANP receptors in rats with experimental heart failure.

Rats with aortocaval (A-V) fistula, an experimental model of congestive heart failure (CHF), display high circulating atrial natriuretic peptide (ANP) levels and a markedly blunted natriuretic response to ANP infusion. The present study was designed to evaluate whether alterations in renal ANP receptors may contribute to renal hyporesponsiveness to ANP in experimental CHF. Densities (Bmax) and dissociation constants (Kd) of both the biologically active (ANPA) and clearance receptors (ANPC) were evaluated in glomerular and papillary membranes from A-V fistula rats (n = 18) and sham-operated controls (n = 20). ANPA and ANPC receptor subtypes were assayed by displacement of 125I-ANP-(99-126) bound to glomerular or papillary membranes by increasing concentrations of unlabeled ANP-(99-126) or des-(18-22)-ANP-(4-23), an analogue which binds only to ANPC. Seven days after the operation, rats with A-V fistula displayed avid sodium retention, elevated plasma renin activity, and approximately a 10-fold increase in plasma ANP levels. Bmax of total ANP binding sites was significantly decreased in rats with A-V fistula compared with controls (220 +/- 61 vs. 399 +/- 88 fmol/mg protein, P < 0.05). The decrease was mainly due to a reduction in ANPA receptor density (51 +/- 10 vs. 110 +/- 15 fmol/mg protein, P < 0.05) with no change in receptor affinity. Likewise, a significant reduction in the density of ANPA (23 +/- 5 vs. 64 +/- 10 fmol/mg protein, P < 0.05) with no change in receptor affinity was observed in papillary membranes of rats with A-V fistula.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic factor influences in vivo plasma, lung and aortic wall cGMP concentrations differently

Atrial natriuretic factor (ANF) promotes natriuresis and diuresis, increases vascular permeability and may induce p]ripheral vasodilation. Endothelium-derived relaxing factor (EDRF), which is nitric oxide (NO), promotes local vasodilatation. ANF and EDRF-NO both cause vascular relaxation by generating cGMP via the activation of the particulate and soluble guanylate cyclases, respectively. This study examines the in vivo effect exogeneous ANF administration in normal Wistar rats, and of increased endogenous ANF in an experimental model of heart failure, on plasma and tissue cGMP concentrations. Low-dose ANF increased plasma and pulmonary cGMP concentrations, whereas 10-fold higher doses were necessary to increase aorta cGMP concentrations. Rats with a myocardial infarction had increased plasma ANF and cGMP and pulmonary cGMP concentrations, but aorta cGMP concentration remained similar to that of sham-operated rats. N G nitro L-arginine methyl ester (L-NAME) was administered chronically to sham-operated and myocardial infarction rats to block NO-synthase: soluble guanylate cyclase activity. L-NAME did not lower the increase in plasma ANF concentration or in urinary, plasma or pulmonary cGMP concentration. In contrast, L-NAME reduced the aorta cGMP concentration 6-fold, despite an increased level of circulating ANF. In summary, the pathophysiological range of plasma ANF concentrations greatly increases plasma and pulmonary cGMP concentrations (by activating particulate guanylate cyclase), but has little influence on the aorta cGMP concentration (which remains mainly dependent on NO-synthase: soluble guanylate cyclase activity).

Discrepancy between plasma and aortic wall cyclic guanosine monophosphate in an experimental model of congestive heart failure

The state of the vasodilator systems in congestive heart failure is poorly defined. Plasma atrial natriuretic peptide is increased, whereas endothelium derived relaxing factor activity can be decreased. Atrial natriuretic peptide and endothelium derived relaxing factor both cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP), by activating the particulate and the soluble guanylate cyclase, respectively. This study examines the biological effects of atrial natriuretic peptide and endothelium derived relaxing factor in experimental heart failure by assessing the plasma, urinary, and tissue concentrations of their common second messenger cGMP. Myocardial infarctions (n = 31) were induced and sham operations (n = 25) were performed on Wistar rats, and the rats were monitored for three months. Aortic and pulmonary cGMP contents were measured, as the aorta is mainly matrix and smooth muscle cells, and the lung is particularly rich in capillaries, hence in endothelial cells. The concentrations of the other second messenger cyclic adenosine monophosphate (cAMP) was also determined, as were those of cGMP dependent protein kinase in the arteries. 17 of the 31 rats with myocardial infarction had oedema. The total heart weight to body weight ratio and the ratio of the myocardium haemodynamically upstream from the infarcted left ventricle to body weight were increased in proportion to the infarct size. Plasma atrial natriuretic peptide and plasma and urinary cGMP concentrations were increased in proportion to the degree of heart failure (p < 0.0001). The pulmonary cGMP concentration was significantly higher in the rats with myocardial infarction than in the control group (p < 0.0001). Pulmonary cGMP concentrations were correlated with the plasma concentrations of atrial natriuretic peptide and cGMP (r2 = 0.59 and 0.66 respectively, p < 0.0001). The cGMP, cAMP, and cGMP, and cGMP dependent kinase concentrations in the aortic wall of rats with myocardial infarctions were the same as in control rats. The increase in plasma, urinary, and pulmonary cGMP in rats with myocardial infarctions were highly correlated with the increase in circulating atrial natriuretic peptide. By contrast, the aortic cGMP concentration was unchanged in these rats, despite high plasma atrial natriuretic peptide. In congestive heart failure, a discrepancy seems to exist between pulmonary (mainly endothelium) and aortic wall (mainly smooth muscle cells) cGMP.

Bradykinin does not modulate the natriuretic response to atrial natriuretic factor in rats with aortocaval fistula.

Rats with aortocaval fistula, an experimental model of congestive heart failure (CHF), display two distinct patterns of sodium excretion: some rats develop marked sodium retention and worsening edema with urinary excretion of sodium (UNaV) < 200 microEq per 24 hours, i.e., uncompensated CHF, whereas in others sodium balance rapidly returns to normal (UNaV > 1,400 microEq per 24 hours), i.e., compensated CHF. Similar patterns of sodium excretion are found in patients with CHF. The mechanisms underlying these responses are not fully understood. The present study was designed to assess whether bradykinin plays a role in the compensatory response to CHF. Infusions of either 10 or 50 micrograms/kg per minute of synthetic atrial natriuretic factor (ANF)8-33 into sham-operated control animals produced significant increases in urine flow and fractional excretion of sodium (FENa). Infusions of ANF at the same doses into rats with compensated CHF increased FENa from 0.11 +/- 0.03% to a maximum of 6.10 +/- 1.30%, whereas the rise in FENa in animals with uncompensated CHF was significantly reduced (0.05 +/- 0.01% to 0.59 +/- 0.18%) compared with sham-operated controls (0.23 +/- 0.05% to 8.32 +/- 1.0%) or the group with compensated CHF. Treatment of the compensated rats with the bradykinin antagonist HOE-140 (D-Arg,[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin) given at a rate of 100 nmol/kg per hour did not affect their renal response to the ANF. In addition, infusion of the bradykinin antagonist alone into compensated rats with aortocaval fistula had no significant effect on their basal urinary flow rate or sodium excretion during the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterisation of plasma and tissue atrial natriuretic factor during development of moderate high output heart failure in the rat.

The aims were (1) to characterise plasma and tissue atrial natriuretic factor (ANF) levels, haemodynamic variables, and renal function at different stages of moderate chronic high output heart failure in the rat; and (2) to assess the contribution of the atria and ventricles to plasma ANF levels. Plasma and tissue ANF levels, haemodynamics, and renal function were evaluated at 1, 2, 4, 8, and 16 weeks after the development of aorto-caval shunts. Sham operated animals served as controls at identical time points. Male Sprague-Dawley rats weighing 225-275 g were used in all experiments. Mean arterial blood pressure was lower and right atrial pressure was higher in the aorto-caval shunt groups than in sham operated controls at all time periods. Left ventricular end diastolic pressure was increased significantly in aorto-caval shunt rats at 1, 2, and 4 weeks when compared with their control counterparts. Plasma COOH terminal and NH2 terminal ANF concentrations were increased significantly in aorto-caval shunt animals. Plasma ANF was positively correlated with right atrial pressure and left ventricular end diastolic pressure in aorto-caval shunt rats but not in sham operated controls. Aorto-caval shunt animals also developed marked cardiac hypertrophy with decreased atrial ANF concentration, but not content, and increased ventricular ANF concentration and content. Despite high plasma ANF concentrations, aorto-caval shunt rats had a lower packed cell volume at all observed periods and reduced urinary sodium excretion and urinary volume at 1 and 2 weeks, with trends to a reduction at 4, 8, and 16 weeks. Body weight was higher in aorto-caval shunt animals at 16 weeks than in sham operated controls. (1) Chronically increased cardiac filling pressure stimulated not only ANF release but also ANF synthesis in each cardiac chamber, which in turn contributed to raised plasma ANF concentrations in aorto-caval shunt rats; (2) an attenuated renal response to endogenous ANF and sodium and water retention were apparent in A-C shunt rats. Activation of neurohormonal vasoconstrictor systems and gradually decreased plasma ANF concentrations may contribute to sodium and water retention at different stages of this experimental model of heart failure.

Pressure overload-induced cardiac hypertrophy with and without dilation

Objectives. The present study was designed to produtce a small animal model showing compensated hypertrophy followed by congestive heart failure within 3 reasonable time period.Background. Although there are various large animal experimental models of hypertrophy and heart failure, the occurrence of these two stages within a reasonable time period has not been shown very successfully in small animals.Methods. A mildly constricting band was placed around the ascending aorta of very young guinea pigs (mean age 25 ± 3 days) to impose a gradually increasing pressure overload. The animals were examined at different postoperative intervals up to 20 weeks.Results. At 10 weeks, there was a 56% increase in ventricular weight/body weight ratio, a 33% increase in left ventricular wall thickness and a significant increase in left ventricular systolic pressure. The animals with 20 weeks of banding had developed various clinical symptoms of congestive heart failure including dyspnea, cyanotic appearance of the extremities, hydrothorax and ascites. Although at this stage there was 86% hypertrophy, the increase in wall thickness was only 20%, indicating cardiac dilation. Depressed left ventricular systolic pressure and increased left ventricular end-diastolic pressure and the increase in wet weight/dry weight ratio in the lungs and liver at 20 weeks also indicated the occurrence of heart failure. The collagen content in the heart of animals with banding for 10 and 20 weeks was 160% and 240%, respectively, of that in corresponding sham control animals.Conclusions. The data suggest that the heart was in a stage of compensated hypertrophy for up to 10 weeks, whereas heart failure was seen at 20 weeks. The two functional stages, compensatory hypertrophy followed by prolonged failure, make this model appropriate for studies on the transition of heart hypertrophy to congestive heart failure.

Energy status of the rapidly paced canine myocardium in congestive heart failure.

Rapid ventricular pacing (RVP) is used as an experimental model of congestive heart failure (CHF). The purpose of this study was to determine the energy status of the dog myocardium after the development of CHF via chronic RVP. The myocardium had a significantly lower (P < 0.05) energy charge (EC) during CHF (0.63 +/- 0.01) than in sham-operated controls (0.82 +/- 0.02). This was due to significant differences in concentrations in ATP (-48%), ADP (29%), and AMP (275%) in the RVP group. However, the total adenine nucleotide pool was not different between groups. Myocardial lactate concentration was also similar. Glycogen was significantly lower (P < 0.05) by 20% at peak CHF. The adenine nucleotides were similar among the different myocardial layers (endo-, mid-, and epicardium). The administration of enalapril (an inhibitor of angiotension-converting enzyme) to decrease vascular resistance had no effect on the myocardial energy status of CHF dogs. These findings suggest that the lower EC in CHF animals is not the result of subendocardial ischemia. Also, lower EC is not associated with endogenous glycogen depletion or increased lactate concentration. The energy status of the myocardium in RVP-induced CHF is unlike that seen in ischemia-induced heart failure. This suggests that CHF in RVP is not vascular in origin.