Contractile dysfunction in postischemic stunned myocardium is driven by decreased myofilament sensitivity to calcium rather than a failure of calcium delivery.
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 degrees C. In stunned myocardium, diastolic Ca2+i (0.24 +/- 0.03 microM) was not changed from control (0.18 +/- 0.03 microM, p greater than 0.10), but peak Ca2+i (1.03 +/- 0.13 microM) was paradoxically higher than that in control (0.61 +/- 0.06 microM, p less than 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 less than 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.
Kusuoka et al. (1990) studied this question.