Recuperative potential of cardiac muscle following relief of pressure overload hypertrophy and right ventricular failure in the cat.

Abstract

This study examined the recuperative potential of cat hearts subjected to experimental right ventricular pressure overload (for a 10- to 14-day period) which provoked hypertrophy with and without congestive heart failure. Five groups of cats were studied: normal controls; one group with 70% pulmonary artery constriction which produced right ventricular hypertrophy (RVH); one group with an 87% constriction which also produced right ventricular hypertrophy but with congestive heart failure (CHF); and two groups which had been similarly subjected to pressure overload but which had been allowed a recovery period of 30 days after relief of the pressure overload. Both the 70% and 87% pulmonic constrictions were associated with extensive right ventricular hypertrophy, depression of myocardial contractile function, and severe redlction of cardiac norepinephrine stores (normal, 1.42 mug/g: RVH, 0.11 mug/g; CHF, 0.01 mug/g). After a 30-day period of relief from the pulmonic constriction normal hemodynamic function returned. In cats in which RVH had been relieved, right ventricular weight and contractile function were normal but catecholamine depletion persisted. Cats with relieved CHF showed depressed contractile function and depleted myocardial norepinephrine, and the right ventricular weight did not return to normal. Cardiac muscle of all pressure-overloaded nonrelieved hearts showed depressed velocity of shortening and depressed ability to sustain load. Cats with RVH alone regained normal muscle shortening velocity and load-bearing ability after relief. However, cardiac muscle from the CHF-relieved group recovered only unloaded shortening velocity while the ability to sustain load remained depressed. We conclude that the recuperative potential of myocardium damaged by pressure overload is adequate provided congestive heart failure has not occurred. Heart failure produces a persistent reduction in force-generating ability of the myocardium. Hypertrophy due to pressure overload, with or without CHF, leads to cardiac catecholamine depletion which is not readily reversed by relief of the overload.

Ventricular performance, pump function and compensatory mechanisms in patients with aortic stenosis.

“…The animals studied had no depression or moderate depression of contractile function in the hypertrophied nonfailing heart and more severe depression of contractile function when heart failure was present.1-4, 6 In these experimental studies, the extent of reduction of contractile function also appeared to be related to the severity of ventricular outflow stenosis.1' 3 The findings of our investigation differ from those of Gunther and Grossman,17 who suggest that poor cardiac performance in patients with aortic stenosis may not be related to depression of myocardial contractility, but rather to increased wall stress and inadequate hypertrophy. Our data show no evidence that inadequate hypertrophy accounts for the failure state since, in our AS-CHF group, systolic wall stress was relatively normalized, ventricular mass was highest, and the ratio of left ventricular mass to enddiastolic volume was not depressed.…”

“…Although previous reports suggest that the prognosis for isolated mitral valve prolapse in childhood is excellent,1 3 syncope and sudden death have been reported and are felt to be related to cardiac arrhythmias.2 The association of mitral valve prolapse with arrhythmias manifested on ambulatory monitoring or stress testing has been well substantiated in adults.4-8 To date, there have…”

“…When the pressure overload is less intense and less acute and when heart failure does not develop, ventricular performance is variable.6 ' 7 In experimental animals, it appears that depression of myocardial function is directly related to the severity of the overload, the presence of congestive failure and, possibly, the duration of the overload. 3,6,7 Despite these experimental studies, ventricular contractile function in patients with chronic pressure overload caused by aortic stenosis is still debated.8 17 From the limited patient studies available, it seems reasonable to postulate that ventricular contractile function is depressed when severe pressure overload has caused congestive failure, but normal when the overload is less severe and failure has not occurred.s9 11,16,17 In this study, we tested this hypothesis by determining hemodynamic values and quantitative ventricular function measurements in three groups of patients. Patients with severe aortic stenosis and congestive heart failure symptoms were compared with patients without heart disease and with patients with significant aortic stenosis but no heart failure symptoms.…”

Complete reversibility of cat right ventricular chronic progressive pressure overload.

“…Following our initial demonstration ) that both the structural and functional abnormalities produced by an abrupt, fixed pressure overload are reversed when the pressure overload is removed, similar observations were made for an abrupt, fixed volume overload (Papadimitriou et al, 1974). When each hemodynamic abnormality was allowed to progress to heart failure, both pressure (Coulson et al, 1977) and volume (Newman et al, 1982) overloads were found to produce irreversible abnormalities. Indeed, we have recently found (Wisenbaugh et al, 1983a) that a severe acute afterload increase produces largely irreversible hypertrophy, even before the progression to heart failure has occurred.…”

Myocardial hydroxyproline and mechanical response to prolonged pressure loading followed by unloading in the cat.

“…It is well accepted that myocardial hypertrophy may regress and depressed myocardial function improve in Received for publication 13 December 1982 and in revised form 1 June 1983. humans (1,2) and experimental animals (3,4) after removal of the hypertrophic stimulus. Unfortunately, this is not a universal occurrence and myocardial dysfunction may persist (1,2,5).…”