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Duration of the Reoxygenation Interval Applied before Ischemic Post-conditioning: Fine-Tuning the Protocol for Human Myocardium

Paula Soler-Ferrer, Kelly Casos, Maria L Perez and Manuel Galinanes

Ischemic post-conditioning (IPostC) is a cardioprotection strategy applied after prolonged ischemia. In an in vitro model of human myocardium we previously demonstrated that one cycle of 120 s of ischemia is the most protective; however the optimal duration of the reperfusion interval between prolonged ischemia and the application of IPostC have not been determined. To investigate the importance of this reperfusion interval, myocardial muscles from the right atrial appendage of 26 patients were subjected to 90 min of ischemia followed by 120 min of reoxygenation. IPostC was induced by four different reperfusion intervals (30, 60, 120 and 180 s) followed by 120 s of ischemia. Lactate dehydrogenase leakage and caspase 3 activity were measured to assess cell injury and apoptosis, respectively. The results showed that intervals of 120 and 180 s were more protective than those of 30 and 60 s, although protection was obtained in only approximately one-third of the patients. Importantly, the muscles from patients receiving nitric oxide donors as anti-anginal agents were not protected by any of the IPostC protocols used. In conclusion, the present study demonstrates the importance of the duration of the reoxygenation interval before the application of IPostC, with 120 and 180 s conferring the greatest protection. This finding is relevant for the design of future studies on the clinical utility of IPostC and on the investigation of the underlying protective mechanisms.