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

Abstract

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 43+0.6 g/mm2 and 49.5±f17.5 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<0.05), and myocardial hydroxyproline content was increased by 160% (p<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.

Remodelamento miocárdico após grandes infartos converte potenciação pós-pausa em decaimento da força em ratos

“…Post-MI remodeling was associated with a depressed tension development in papillary muscles from infarcted rats and reduced Bocalini et al Post-rest decay in myocardium from infarcted rats rate of force generation and relaxation, as previously reported for papillary muscles 9,10,13,20,24 . Similar impairment of shortening was identified in isolated ventricular myocytes as well 25,26 , and the proposed mechanisms explaining the contractile dysfunction include defects in the excitation-contraction coupling 13,24 .…”

Performance of two-dimensional Doppler echocardiography for the assessment of infarct size and left ventricular function in rats

“…The rat model of myocardial infarction has been used for decades in many research laboratories to study left ventricular function (1-3), remodeling (4,5), the impact of pharmacological (6,7) or surgical interventions (8), and recently, the effect of gene transfer and cell transplantation (9,10). Two-dimensional echocardiography is widely used in humans with acquired or congenital diseases, particularly in patients with myocardial infarction during the acute phase and for late follow-up (11).…”

Effects of lisinopril on experimental ischemia in rats. Influence of infarct size

“…Some authors 23,25 have found that ACEIs decrease the tissue amount of collagen. Other authors 17,22 , however, have not shown interference of the treatment in the intensity of the postinfarction fibrosis.…”

“…Despite being an indirect quantitative method, a close correlation between the biochemical method and the amount of collagen analyzed by morphometry was found 20,21 . This allowed the concentration of hydroxyproline to be accepted as a parameter for the amount of collagen, in this model 22,23 .…”