Alterations of excitation-contraction coupling in stunned myocardium and in failing myocardium

D. Atar, W. D. Gao and E. Marban. Alterations of Excitation-Contraction Coupling in Stunned Myocardium and in Failing Myocardium. Journal of Molecular and Cellular Cardiology (1995) 27, 783-791. Although both myocardial stunning and chronic heart failure are characterized by contractile dysfunction, there are profound differences in their underlying mechanisms. Changes in cardiac contractile force can be effected by modulation of intracellular [Ca²⁺] or by alteration of the contractile protein response to intracellular Ca²⁺. New evidence suggests that the principal lesion in the stunned myocardium resides at the level of the contractile proteins, which may be injured by proteases activated early during reperfusion. In contrast, failing myocardium is known to display abnormal intracellular Ca²⁺ handling, indicative of dysfunction of the sarcoplasmic reticulum. Alterations of gene expression and isoform switching of the myofilaments also occur in failing myocardium, consistent with an observed shift of the kinetics of crossbridge cycling. In conclusion, changes in both intracellular Ca²⁺ homeostasis and myofilament function occur in failing myocardium, while stunned myocardium primarily reflects an uncoupling between Ca²⁺ and contractile force.