EXCITATION-CONTRACTION COUPLING IN POSTISCHEMIC MYOCARDIUM - DOES FAILURE OF ACTIVATOR CA-2+ TRANSIENTS UNDERLIE STUNNING

To elucidate the mechanism of contractile dysfunction in postischemic ('stunned') myocardium, time-resolved measurements of intracellular free Ca2+ concentration ([Ca2+](i)) were made using gated 19F nuclear magnetic resonance in seven perfused ferret hearts loaded with the fluorinated Ca2+ indicator 5F-BAPTA. Left ventricular developed pressure decreased to 65 ± 3% (mean ± SEM) of control after 15 minutes of global ischemia at 37°C. In stunned myocardium, diastolic [Ca2+](i) (0.24 ± 0.03 μM) was not changed from control (0.18 ± 0.03 μM, p > 0.10), but peak [Ca2+](i) (1.03 ± 0.13 μM) was paradoxically higher than that in control (0.61 ± 0.06 μM, p < 0.02). The slope of the relation between developed pressure and Ca2+ transient amplitude in stunned myocardium was significantly lower than that in control (p < 0.05), even after normalization by maximal Ca2+-activated pressure. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to the previously identified decrease in maximal Ca2+-activated force; failure of activator Ca2+ delivery cannot be implicated. The increase in the amplitude of Ca2+ transients would require that more ATP be spent in Ca2+ sequestration; thus, decreased efficiency of energy utilization in stunned myocardium would result.