Calcium and Its Role in Myocardial Cell Injury During Ischemia and Reperfusion

Marban, Eduardo MD, PhD
Koretsune, Yukihiro MD, PhD
Corretti, Mary MD
Chacko, V. P. PhD
Kusuoka, Hideo MD, PhD

Division of Cardiology, Department of Medicine, and the Division of Nuclear Magnetic Resonance Research, Department of Radiology (V.P.C), The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Address for correspondence: Eduardo Marban, MD, PhD, Hunterian 116, Division of Cardiology, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205.

Circulation 80(6):p IV-22, December 1989.

Direct measurements of intracellular free Ca²⁺ concentration ([Ca²⁺]_i) were obtained during ischemia and reperfusion in ferret hearts loaded with the Ca²⁺ indicator, the 5,5'-difluoro derivative of 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′,-tetraacetic acid. During 15 minutes of ischemia at 370° C, time-averaged [Ca²⁺]_i increased significantly and decreased rapidly during reperfusion. In contrast to metabolic inhibition in isolated muscle or cells, the increase in [Ca²⁺]_i during true ischemia occurs in the absence of a mechanical contracture. After ischemia, contractile function does not recover completely: the hearts are “stunned.” Our results support the hypothesis that an increase in cellular calcium-loading causes dysfunction in the form of myocardial stunning while leaving binresolved the precise mechanism of the calcium-mediated injury.