To investigate excitation-contraction coupling in
stunned myocardium, intracellular free
calcium concentration [( Ca2+]i) was measured before and after
ischemia in perfused hearts using gated 19F NMR and the Ca2+
indicator 5F-BAPTA. Maximal Ca(2+)-activated force was also measured in parallel experiments.
Stunned myocardium was created by reperfusion after 15 min global
ischemia at 37 degrees C in isolated ferret hearts. In
stunned myocardium, peak [Ca2+]i was paradoxically higher than that in control, but maximal Ca(2+)-activated pressure was lower in stunned hearts. These results indicate that contractile failure in
stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to a decrease in maximal Ca(2+)-activated force; failure of activator Ca2+ delivery cannot be implicated. The role of intracellular
calcium overload in the pathogenesis of
stunned myocardium was also investigated. Time-averaged 19F NMR measurements directly revealed the increase in [Ca2+]i during
ischemia and in the early phase of reperfusion. The strategies to prevent Ca overload during reperfusion with modified reperfusate succeeded in preserving contractile function. Transient Ca overload without
ischemia induced by different causes, i.e., high [Ca]0 perfusion,
ventricular fibrillation or treatment with
adriamycin, also produced contractile dysfunction that outlasted the interventions themselves. Thus, we propose that transient Ca overload during
ischemia and early reperfusion initiates long-lasting contractile dysfunction in
stunned myocardium.