RELATIONSHIP BETWEEN INTRACELLULAR CALCIUM AND CONTRACTILE-FORCE IN STUNNED MYOCARDIUM - DIRECT EVIDENCE FOR DECREASED MYOFILAMENT CA2+ RESPONSIVENESS AND ALTERED DIASTOLIC FUNCTION IN INTACT VENTRICULAR MUSCLE

To elucidate the abnormalities of excitation-contraction coupling in s tunned myocardium, we measured [Ca2+](i) and force in thin fura 2-load ed ventricular trabeculae from control or stunned (20 minutes ischemia followed by 20 minutes reflow at 37 degrees C) rat hearts. At any giv en [Ca2+](o), force development was significantly lower in the stunned trabeculae than in control trabeculae. In contrast, there was no diff erence in the amplitude of Ca2+ transients between the two groups. The steady state force-[Ca2+](i) relationship, assessed by tetanization i n the presence of ryanodine, revealed both a decrease in maximal Ca2+- activated force and an increase in the [Ca2+](i) required for 50% acti vation in stunned trabeculae. Postischemic myocardium also exhibited a n accelerated rate of diastolic relaxation that was not due to changes in the rate of Ca2+ transient decay. Destabilization of attached cros s-bridges in a quantitative model of cardiac myofibrils accurately rep roduced the salient systolic and diastolic features of the stunned phe notype, suggesting an abnormality of the thin filaments. In response t o supraphysiological increases in [Ca2+](o), diastolic [Ca2+](i) and d iastolic tone increased much more in stunned trabeculae than in contro ls, with the frequent occurrence of aftercontractions. This novel expe rimental model lends further support to the hypothesis that the primar y lesion of excitation-contraction coupling resides at the level of th e contractile proteins. The finding of enhanced susceptibility to calc ium overload helps to rationalize the functional deterioration of stun ned myocardium during intense inotropic stimulation and additionally s uggests that stunned myocardium may represent a favorable substrate fo r triggered arrhythmias.