Abstract 1594: Increased Apoptosis in Compensated Pressure Overload is not Related to the Extent of Hypertrophy and Occurs in Interstitial Non-Myocytes
A number of studies have indicated a direct relationship between the degree of apoptosis and the severity of left ventricular (LV) hypertrophy (H). However, most of these studies have been carried out in animal models in which pressure overload causes myocardial fiber stretching, as assessed by LV dilation and an increase in LV end diastolic pressure (EDP). In addition, these studies did not discern whether the apoptosis occurred in myocytes or other cell types in the cardiac interstitium. To study the frequency of apoptosis associated with LVH in the absence of fiber stretching, we studied a canine model in which pressure overload, from chronic aortic stenosis, results in a model of concentric LVH, with doubling of LV/body weight, but where the LV is not dilated and LV systolic function, as assessed by LV dP/dt max, (3433±188 mmHg/sec) and LV end diastolic pressure (12±2 mmHg) is normal. The TUNEL method was used to assess changes in apoptosis in cardiac myocytes and interstitial cells in the presence of LVH. Myocyte cross-sectional area was calculated histologically. In control dogs (n=4), the rate of apoptosis in myocytes was 0.03±0.01%. The rate of apoptosis in dogs with LVH (n=6) did not increase significantly, and there was a negative correlation (r= −0.51) between the extent of LVH and the increased apoptotic rate, which was also non-significant. In marked contrast, the rate of apoptosis of non-myocytes (interstitial cells) rose from normal values of 0.03±0.01% to 0.13±0.03%, p<0.05, although they also demonstrated a negative correlation (r= −0.30) between the extent of LVH and the increased apoptotic rate. Myocyte size was larger, P<0.05, in the epicardium (504±5 micron2) than in the endocardium (396±4 micron2) of LVH dogs, but the apoptotic rate was similar in both endo and epicardium, demonstrating further a lack of association between LVH and myocyte apoptosis. Thus, myocyte apoptosis does not increase in response to pressure overload LVH in the absence of LV dilation and elevated LVEDP, suggesting that it is the LV dilation and stretching of myocardium, superimposed on LVH, which may be responsible for the prior reports of increased apoptosis.