Role of calcium and other ions in reperfusion injury

Calcium-related mechanisms may play a role in several aspects of reperfusion injury. One proposal is that internal cytosolic calcium concentration is elevated early in the reperfusion period and that excess oscillations of calcium can very significantly contribute to reperfusion ventricular arrhythmias. Alternate hypotheses, such as those involving free radicals and the local tissue renin-angiotensin system, can be married to the existing hypothesis. Furthermore, the hypothesis allows for a role of the sodium-calcium exchange system and the proton-sodium exchanger. The hypothesis also provides an explanation for "stunning," as it is proposed that early excessive cytosolic calcium damages the organelles regulating the contractile cycle, which subsequently develops into imperfect functioning of the contractile apparatus. Calcium antagonist drugs given during the ischemic period may lessen reperfusion injury by decreasing the severity of ischemic damage. When given at the time of reperfusion, results are complex and to some extent conflicting. The biggest challenge is to understand how relatively low doses of calcium antagonists given after the onset of reperfusion help to decrease delayed reperfusion "stunning." A logical but untested proposal is that calcium antagonists help to prevent delayed contraction-band necrosis, one of the causes of delayed no-reflow.