Contractility and stiffness of noninfarcted myocardium after coronary ligation in rats. Effects of chronic angiotensin converting enzyme inhibition.

BACKGROUND

Previous studies have shown that global left ventricular function is depressed after myocardial infarction. However, little is known about the effects of myocardial infarction on contractility and the passive-elastic properties of residual myocardium.

METHODS AND RESULTS

We evaluated isometric function and passive myocardial stiffness in isolated, noninfarcted left ventricular papillary muscle from rats 6 weeks after sham operation or myocardial infarction. Maximal developed tension and peak rate of tension rise (+dT/dt) were significantly decreased in untreated rats with large myocardial infarction compared with controls (3.3 +/- 1.1 versus 4.3 +/- 0.6 g/mm2 and 49.5 +/- 17.5 versus 72.5 +/- 10.5 g/mm2/sec, respectively). Time to peak tension was prolonged (120 +/- 8 versus 102 +/- 4 msec) and myocardial stiffness was increased in untreated myocardial infarction rats compared with controls (35.2 +/- 4.9 versus 24.2 +/- 3.7). Rats with smaller myocardial infarctions differed from controls only with respect to a prolongation of time to peak tension. Papillary muscle myocyte cross-sectional area was increased by 44% (p less than 0.05), and myocardial hydroxyproline content was increased by 160% (p less than 0.05) in rats with large myocardial infarctions compared with controls. To determine whether treatment that improves left ventricular function after myocardial infarction also improves myocardial function, rats were treated with captopril beginning 3 weeks after myocardial infarction and continuing for 3 weeks. Treatment with captopril attenuated the prolongation in time to peak tension in the myocardial infarction rats; however, developed tension, +dT/dt, and muscle stiffness remained abnormal. Compared with untreated myocardial infarction rats, captopril-treated myocardial infarction rats had a 9% decrease in myocyte cross-sectional area (p = 0.1) but a persistent increase in myocardial collagen content. In summary, large myocardial infarction in rats causes contractile dysfunction, increased stiffness, myocyte hypertrophy, and increased collagen content in the residual noninfarcted myocardium. Treatment with captopril alters the process of cardiac remodeling and hypertrophy and improves one parameter of contractility in noninfarcted myocardium; however, myocardial collagen content and myocardial stiffness remain abnormal.

CONCLUSIONS

These findings suggest that angiotensin converting enzyme inhibition in the rat infarct model of heart failure improves global cardiac performance via combined effects on myocardial function and the peripheral circulation.