IMPAIRED MYOCARDIAL-FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS WITH HEART-FAILURE

We have observed that many spontaneously hypertensive rats (SHR) between the ages of 18 and 24 mo develop findings suggestive of heart failure, including pleural and pericardial effusions, left atrial thrombi, and right ventricular hypertrophy. Isolated left ventricular papillary muscle function was studied in these animals (SHR-F), in age-matched SHRs without evidence of heart failure (SHR-NF), and in nonhypertensive controls (WKY). Preparations from SHR-F showed depression of active tension development (3.58 +/- 1.75 g/mm2; means +/- SD) compared with both SHR-NF (7.17 +/- 0.94) and WKY (6.17 +/- 1.00) (P < 0.01). Shortening velocity was also depressed in SHR-F (0.95 +/- 0.38 lengths/s) compared with SHR-NF (1.60 +/- 0.30; P < 0.05) and WKY groups (2.15 +/- 0.48; P < 0.01). Depression of muscle function was not found before 18 mo of age. Thus the aging SHR is a model in which one can observe the transition from chronic stable left ventricular hypertrophy to overt heart failure. Furthermore, left ventricular papillary muscles from SHRs with heart failure show evidence of significant contractile dysfunction, suggesting that impairment of intrinsic myocardial function underlies the development of heart failure.