Cellular mechanisms of hypertrophic cardiomyopathy in spontaneously hypertensive rats (SHR)

Abstract

It is shown that the weight dynamics of the body, heart and left ventricular myocardium is similar in Wistar rats and SHR, but the number of cardiomyocytes in the 5th and 24th weeks of postnatal development is considerably higher in Wistar rats than in SHR. The earlier maturation of cardiomyocytes in SHR rats leads to their reduced proliferative activity, thus blocking the growth of the cell population. Key Words: cardiomyocytes; hypertrophy; spontaneously hypertensive rats (StfR); cell population sizeModeling of hereditary cardiomyopathy is of great importance for elucidating the general pathways of heart pathology in man. Hypertrophic cardiomyopathy in spontaneously hypertensive rats (SHR) is considered to be one such model [6,10,12,13]. Myocardium hypertrophy in these animals develops at an early age and has been shown not to be directly related to the development of arterial hypertension [8,9]. Morphogenesis of myocardium hypertrophy, the pattern of ultrastructural changes in cardiomyocytes, and the spatial tissue and intracellular rearrangement of the myocardium in SHR are similar in many features to the morphological rnardfestation of hypertrophic cardiomyopathy in man and have been described at length [1,[3][4][5]. However, the causes of the development of myocardium hypertrophy in SHR remain quite uncertain; in particular, little is known about the ratio between proliferative processes (or hyperplasty) and hypertrophy of cardiomyocytes in early ontogeny and their contribution to myocardium hypertrophy in SHR.The objective of the present investigation was to compare the dynamics of cardiomyocyte population growth in postnatal ontogeny in Wistar rats and SHR. MATERIALS AND METHODSThirty-two Wistar rats (controls) and 21 SHR (both 1 day old) were selected for the experiments. Ten Wistar rats and 9 SHR were killed at the start point and the others after attaining the 5-or 24-week age. All the animals were weighed before sacrifice. The hearts were fixed by perfusion with 10% paraformaldehyde in 0.1 M phosphate buffer saline (pH 7.2) until the myocardium was completely washed free of blood. After the atrii were removed, the myocardium of both ventricles (total heart weight) and of the left ventricle with the interventricular septum were weighed. Alkaline dissociation of the fixed myocardium was performed according to a standard procedure [7].

Cellular mechanisms of genetically determined hypertrophic cardiomyopathy in W/SSM rats

“…Plenum Publishing Corporation titative analysis of the CM population was performed after alkaline dissociation [10,11]. The myocardium was fixed for 14 days, and then washed with 0.1 M phosphate buffer (pH 8.0) for 24 h, tissue specimens (20-25 mg) were incubated in 50% KOH for 18 h at 8~ The CM suspension thus obtained was stained with 0.1% etidium bromide.…”

“…[10]. Therefore, purestrain animals with genetically determined cardiac pathology are the most suitable models for a detailed study of the mechanisms and patterns of cardiomyopathies [2][3][4][5]10,15]. Despite the fact that hypertrophic cardiomyopathy is a common disease, it is one belonging to the noncoronarogenic group, which has not been studied in depth [7,8].…”

“…It is shown that the increase in the myocardium mass results at first predominantly from an increase in the number of cardiomyocytes and then, after exhaustion of the proliferative potential, from cardiomyocyte hypertrophy. [10]. Therefore, purestrain animals with genetically determined cardiac pathology are the most suitable models for a detailed study of the mechanisms and patterns of cardiomyopathies [2][3][4][5]10,15].…”