Cellular Mechanisms of Contractile Dysfunction in Hibernating Myocardium

Abstract

Abstract-Ischemic heart disease is a leading cause of chronic heart failure. Hibernation (ie, a chronic reduction of myocardial contractility distal to a severe coronary stenosis and reversible on revascularization) is an important contributing factor. The underlying cellular mechanisms remain however poorly understood. In young pigs (nϭ13, ISCH), an acquired coronary stenosis Ͼ90% (4 to 6 weeks) resulted in the development of hibernating myocardium. Single cardiac myocytes from the ISCH area were compared with cells from the same area obtained from matched normal pigs (nϭ12, CTRL). Myocytes from ISCH were larger than from CTRL. In field stimulation, unloaded cell shortening was reduced and slower in ISCH; relaxation was not significantly different.

Remodeling of T-Tubules and Reduced Synchrony of Ca 2+ Release in Myocytes From Chronically Ischemic Myocardium

“…32 After enzymatic digestion of the tissue wedge perfused by the stenotic artery, the infarct area and 5 to 10 mm around the infarct core were discarded; midmyocardial cells from the remaining digested tissue were used. Myocytes isolated from the midmyocardial layer of the posterior wall of the weight-matched healthy pigs served as controls.…”

Investigating Cardiac Function Using Motion and Deformation Analysis in the Setting of Coronary Artery Disease

“…It was shown that contraction of an isolated myocyte from a chronically ischemic segment will be reduced but prolonged, 64 indicating that the duration of the active force is of importance for the resulting deformation. As well as the active contraction, tissue properties (mainly elasticity) will change in chronic ischemia because of the development of fibrosis.…”

Molecular Basis of Arrhythmias

“…114 Studies of electrical remodeling in models of hibernating myocardium have demonstrated prolonged action potential duration and impaired intracellular Ca 2ϩ handling. 115,116 Preliminary studies have noted an increase in the depolarizing L-type Ca current; however, evaluation of repolarizing K ϩ currents has not been reported. 116 Reperfusion of ischemic myocardium, as may occur in patients with coronary artery disease, is associated with increased susceptibility to VF.…”

“…115,116 Preliminary studies have noted an increase in the depolarizing L-type Ca current; however, evaluation of repolarizing K ϩ currents has not been reported. 116 Reperfusion of ischemic myocardium, as may occur in patients with coronary artery disease, is associated with increased susceptibility to VF. Electrophysiological cell and tissue properties that characterize ischemic and reperfused myocardium help to rationalize the frequency of reperfusion arrhythmias.…”