Postresuscitation Stunning: Postfibrillatory Myocardial Dysfunction Caused by Reduced Myofilament Ca2+ Responsiveness After Ventricular Fibrillation‐Induced Myocyte Ca2+ Overload

INTRODUCTION: Resuscitation from ventricular fibrillation (VF), particularly from prolonged VF, frequently is complicated by postfibrillatory myocardial dysfunction (postresuscitation stunning). We tested whether this dysfunction can be caused by reduced myofilament Ca2+ responsiveness after VF-induced myocyte Ca2+ overload. We also tested whether electrical defibrillation shocks contribute to this dysfunction. METHODS AND RESULTS: Myofilament Ca2+ responsiveness was estimated as ratio of left ventricular developed pressure over myocyte Ca2+ transient amplitudes (assessed as indo-1 fluorescence) in isolated perfused rat hearts before, during, and after VF (1.5 or 10 min) comparing three modes of defibrillation (biphasic electrical shocks, lidocaine, or spontaneous). We found that, independent of these defibrillation modes, myofilament Ca2+ responsiveness was significantly reduced, particularly after prolonged VF, although hearts were not ischemic or acidotic during and after VF (unchanged coronary flow, myocardial oxygen consumption, and pH of the coronary effluent). This reduction was associated with VF-induced myocyte Ca2+ overload and increasing or decreasing Ca2+ overload during VF (using 1 microM diltiazem or 6 mM extracellular calcium) led to parallel changes of myofilament Ca2+ responsiveness. However, myofilament Ca2+ responsiveness was not associated with the defibrillation shock energy (range 0.1-15.0 J/g wet heart weight). CONCLUSION: Postfibrillatory myocardial dysfunction can be caused by reduced myofilament Ca2+ responsiveness after VF-induced myocyte Ca2+ overload. Electrical defibrillation shocks (up to 15 J/g wet heart weight), however, do not significantly contribute to this dysfunction. Our findings suggest that early additional therapy targeting intracellular Ca2+ overload may normalize myocyte Ca2+ and partially prevent postresuscitation stunning.