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— Adaptations of the aging left ventricle (LV) to hemodynamic overload are functionally and structurally distinct from those of the young organism. This study describes the influence of aging on LV hemodynamics and remodeling late after myocardial infarction (MI) in Fischer 344 Brown Norway rats. In sham rats at 23 mo, LV weight, myocyte cross-sectional area (CSA), and myocardial fibrosis were increased, whereas LV dP/d t, LV relaxation, and maximal LV systolic function declined with respect to younger rats (7, 12, and 18 mo of age). Isometric myocardial function was evaluated in papillary muscles of 12- and 23-mo-old sham rats. Myocardial systolic function was decreased in older rats. To determine how aging affects LV function and remodeling after MI, rats were infarcted at 7 and 18 mo of age and were studied 5 mo later. Infarct size was similar in each group. Right ventricular weight, LV end-diastolic pressure, and volume index were increased, whereas LV dP/d t, peak cardiac index, and peak developed LV pressure declined after MI. However, there were no significant differences between young and older rats in any variable of LV systolic function or remodeling after MI. Myocyte CSA increased in younger rats after MI but was unchanged in 23-mo-old rats. After MI, myocardial fibrosis was significantly increased from baseline only in younger rats. The negative interaction of aging and MI on myocyte hypertrophy and fibrosis was highly significant. The findings indicate that baseline LV and myocardial function decline with age. In the aging rat after MI, despite limited compensatory hypertrophy and more advanced baseline myocardial fibrosis, the long-term functional and structural adaptations to MI are similar to those of the mature adult heart.

To determine the role of angiotensin II-receptor blockade on cardiovascular remodeling in a pressure-overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult male Sprague-Dawley rats. Aortic-banded (AB) rats were left untreated or were losartan (Los; 250 mg/l) treated (AB-Los). Sham-operated (S) controls were either left untreated or treated with Los (S-Los). After 4 wk, rats were catheterized for measurement of mean arterial pressures [carotid (CMAP) and femoral (FMAP), in mmHg]. Hearts were perfused on a modified Langendorff system, and minimal coronary resistance (MCR) was determined. Hearts were then perfusion fixed, total and regional heart weights were recorded, and sections were processed for morphology. Changes in coronary artery medial thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Los than in S or S-Los (P < 0.05). There was no difference in FMAP in AB vs. S, but AB-Los and S-Los had lower FMAPs than S. Total heart weight and left ventricular weight-to-body weight ratios were increased in AB and AB-Los compared with S and S-Los (P < 0.05). MCR of AB was greater than S and S-Los. MCR of AB-Los was significantly lower than AB and was not significantly different from S and S-Los. In coronary vessels, medial thickness was greatest in AB, whereas there was no difference among AB-Los, S, and S-Los. Similarly, the increase in perivascular fibrosis was greatest in AB, and there was no difference among AB-Los, S, and S-Los. These data suggest that angiotensin II, independent of increased arterial pressure, is critical for the development of the vascular and fibrotic changes that occur in this model of pressure-overload hypertrophy.