Calcium and ischemic injury

Ischemia increases [Ca(2+)](i) in cardiac myocytes despite the initial decrease in force development observed. This increased [Ca(2+)](i) contributes to myocyte injury by diverse mechanisms, including activation of proteases and phospholipases, and mitochondrial injury. Increased [Ca(2+)](i) may also contribute to reperfusion injury by causing hypercontracture when ATP is resynthesized to allow Ca(2+)-induced cycling of the myofilament cross-bridges. In addition, enhanced cellular Ca uptake by Na-Ca exchange, resulting in Ca(2+) loading of mitochondria or other intracellular organelles during reperfusion, may alter postreperfusion recovery. Thus, alterations in Ca(2+) homeostasis probably contribute to ischemic injury; however, other injury pathways not involving an increase in [Ca(2+)](i) or total cellular Ca content are also undoubtedly important.