The role of cyclosporine in the treatment of myocardial reperfusion injury.

Richdeep S Gill, David L Bigam, Po-Yin Cheung

Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.

Shock (Augusta, Ga.) 2012 Apr

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Myocardial injury in adult, pediatric, and newborn patients is a leading cause of mortality and morbidity. Although the underlying etiologies are different among patient populations, the sequence of initial ischemic-hypoxic injury followed by secondary myocardial reperfusion injury is relatively consistent. Overall infarct size is important because it is believed to be a key determinant of mortality. The detrimental effects of myocardial reperfusion have been proposed to be at least partially related to the formation of mitochondrial permeability transition pore (MPTP). The MPTP is a nonspecific pore, which forms during myocardial reperfusion and allows the release of apoptotic signaling molecules and may also lead to cellular necrosis. Cyclosporine A has been shown to be a potent inhibitor of the MPTP, leading to its study as a potential treatment to limit myocardial reperfusion injury. Multiple adult animal models have demonstrated the protective effects of cyclosporine in ischemia-reperfusion. A recent human pilot clinical trial also reported reduced myocardial injury and infarct size in patients treated with cyclosporine intravenously before percutaneous coronary intervention for ST-elevation myocardial infarction. Despite the paucity of evidence of cyclosporine A demonstrating myocardial protection in pediatric and newborn patients, the existing animal experimental results are promising.

Citation

Richdeep S Gill, David L Bigam, Po-Yin Cheung. The role of cyclosporine in the treatment of myocardial reperfusion injury. Shock (Augusta, Ga.). 2012 Apr;37(4):341-7