CALCIUM AND ISCHEMIC-INJURY

Ischemia increases [Ca2+]i in cardiac myocytes despite the initial decrease in force development observed. This increased [Ca2+]i contributes to myocyte injury by diverse mechanisms, including activation of proteases and phospholipases, and mitochondrial injury. Increased [Ca2+]i may also contribute to reperfusion injury by causing hypercontracture when ATP is resynthesized to allow Ca2+-induced cycling of the myofilament cross-bridges. In addition, enhanced cellular Ca uptake by Na-Ca exchange, resulting in Ca2+ loading of mitochondria or other intracellular organelles during reperfusion, may alter postreperfusion recovery. Thus, alterations in Ca2+ homeostasis probably contribute to ischemic injury; however, other injury pathways not involving an increase in [Ca2+]i or total cellular Ca content are also undoubtedly important.