Pumping ability of the hypertrophying left ventricle of the spontaneously hypertensive rat.

Abstract

SUMMARY Cardiac pumping ability was assessed during the natural development of left ventricular hypertrophy by elevating venous pressure by infusing Tyrode's solution intravenously to produce peak cardiac output. This experiment was performed on spontaneously hypertensive rats (SHR) of three age groups (11, 24, and 83 weeks). From 11 to 24 weeks, peak cardiac output of SHR increased in direct proportion to the abnormally increased ventricular mass; Thus peak cardiac output per gram of left ventricle (LV) remained stable. Similar results were obtained for two strains of normotensive rats at each of the same three age groups. Thus, in the normotensive animal peak cardiac output per gram of LV remained stable over a wide range of ages and varying left ventricular weights. However, with progressive elevation of arterial pressure in aging SHR (83 weeks), we observed severe ventricular hypertrophy (100% increases in left ventricular to body weight ratio). In this oldest SHR group, unlike age-matched normotensive rats, there was a marked reduction in the pumping ability per gram of LV. Thus, during the natural development of left ventricular hypertrophy SHR demonstrated both a stable stage of hypertrophy in which the increased left ventricular mass maintained its pumping ability, and a later stage of deterioration in which there was a loss of the normal relationship between ventricular mass and pumping ability.STUDIES ON the mechanical performance of models of pressure-induced ventricular hypertrophy have produced conflicting results. Thus, contractile function in experimental models of both right and left ventricular isometric hyperfunction has been reported as supranormal, 1 ' 3 normal,* and depressed.6 ' 8 These experiments have used the rat, 1 -' dog, 2 -3 and cat. 4 -6 The most common means for producing pressure-induced ventricular hypertrophy has been by the surgical production of outflow tract obstruction or banding, a method which rapidly increases ventricular mass while often depressing contractile performance.Meerson 7 described three stages in the development of ventricular hypertrophy. In the first stage, before myocardial mass increases, contractile function is impaired. Subsequently, during the second stage myocardial mass increases to maintain normal myocardial function; however, in Meerson's third stage there is a progressive deterioration of myocardial function, and eventually cardiac failure is believed to supervene. In contrast, the development of ventricular hypertrophy has been characterized by others as a progressive downhill course leading to overt failure. 8 In support of this latter observation, many experimental models of pressure-induced ventricular hypertrophy failed to demonstrate Meerson's second stage of stable ventricular hyperfunction.Williams and Potter 4 recently have reported that the contractile function of the hypertrophied right ventricle (from cats in which the pulmonary artery was banded) was reduced at six weeks but returned to normal levels after 24 weeks of banding. They sug...

Carrier‐mediated transport controls hydroxyproline catabolism in heart mitochondria from spontaneously hypertensive rat

“…On the other hand, a change in Km suggests a modification in the substrate binding site, assumed to be consistent with a change in the carrier molecule structure (see mersalyl experiment). Nevertheless, given that non-hemodynamic factors, such as circulating hormones, also represent growth stimuli to cardiac fibroblasts and contribute to structural remodeling of the cardiac interstitium during hypertension, it may be reasonable to suggest a role for these factors in the catabolic pathway of collagen [35]; indeed, collagenase activity was found to be affected by angiotensin II [36,371. A better understanding of the pathophysiological basis for fibrosis and the mechanisms responsible for fibroblast collagen turnover is of particular importance in hypertension because of the varied alterations in cardiac performance at different stages [38,39], and the possibility of reversing abnormal accumulation of fibrillar collagen with antihypertensive therapy [4043].…”

Left ventricular function of concentric hypertrophied heart after chronic pressure overload as studied in the isolated canine heart preparation.

“…Secondly, a shift in myosin enzyme in the above animals did not seem to occur or was not of physiological significance (LoMPRE et al, 1981;WISENBAUGH et al, 1983). Thirdly, recent studies found no alteration in ventricular function when the gain in the left ventricular mass to body weight ratio was from 25 to 65 % of that of the control (CARABELLO et al, 1981;PFEFFER et al, 1976;SASAYAMA et al, 1976; T. NAKAMURA, T. KIMURA, S. ARAI, M. MOTOMIYA, and N. SUZUKI WISENBAUGH et al, 1983). In our experiment, the banded animals showed an average of 51.4 % increase in left ventricular mass relative to body weight.…”

“…When evaluated by the value of Emag and ejection fraction determined by the experiment, the ventricular function seemed to be improved, but there was no increase in stroke volume due to the concomitant decrease in EDV. Several investigators measured cardiac output, stroke volume, stroke work, peak dp/dt, and mean VCf of the pressure-overload heart and reported no functional impairment at rest or during exercise (CARABELLO et al, 1981;MALIK et al, 1974;PFEFFER et al, 1976;SASAYAMA et al, 1976). On the other hand, SASAYAMA et al (1977) demonstrated hyperfunction as a pump of these hearts based on the increased wallshortening velocity in comparison with that of the control at a matched level of systolic pressure.…”

“…The following three possibilities have been reported on the basis of experiments as the causes for the depression of the inotropic state under pressure overload : (1) acute myocardial injury after a sudden increase of pressure load (MEERSON, 1965), (2) shift in myocardial isozyme (WIKMAN-COFFELT, et al, 1982), and (3) severe hypertrophy after sustained pressure load (MEERSON,1965;PFEFFER et al, 1976;SPANN et a!., 1967). However, data which are opposed to the above notions have also been published.…”

Hypertension.

“…There is another reason to avoid use of an agent other than whole blood. The lowered viscosity at the end of the infusion period reduces peripheral resistance and may account for the fall in arterial blood pressure observed by Pfeffer et al 1 at the peak of the function curve. Because changes in afterload are a determinant of left ventricular pumping ability, a fall in peripheral resistance should be avoided.…”