Congestive heart failure after myocardial infarction in the rat: cardiac force and spontaneous sarcomere activity.

The causes of reduced cardiac force development in congestive heart failure (CHF) are still uncertain. We explored the subcellular mechanisms leading to decreased force development in trabeculae from rats with a myocardial infarction. We defined CHF according to clinical and pathological criteria and compared properties of trabeculae from animals with CHF (cMI) to those of animals with a myocardial scar but without evidence of CHF (uMI), and sham-operated animals. The new findings of this study on properties of cMI trabeculae are that (1) maximal twitch force following post-extrasystolic potentiation is unchanged; (2) the sensitivity of cMI trabeculae to [Ca(2+)](o) is increased; (3) spontaneous diastolic sarcomere length (SL) fluctuations (SA) are increased in cMI at all levels of SR Ca(2+) loading; and (4) SA is accompanied by a proportional reduction of F(max). The results suggest that the probability of spontaneous diastolic opening of SR Ca(2+) channels is increased in CHF. These data provide the basis for a novel mechanism underlying systolic and diastolic dysfunction as well as arrhythmias in hearts in CHF. If SA proves to be a component of myocardial dysfunction in human CHF, our thinking about therapy of the patient with CHF may be profoundly changed.