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BackgroundThe diseased human myocardium is highly susceptible to ischemia/reoxygenation (I/R)-induced injury but its response to protective interventions such as ischemic preconditioning (IPreC) is unclear. Cardiac and other pre-existing clinical conditions as well as previous or ongoing medical treatment may influence the myocardial response to I/R injury and protection. This study investigated the effect of both on myocardial susceptibility to I/R-induced injury and the protective effects of IPreC.Methods and resultsAtrial myocardium from cardiac surgery patients (n = 300) was assigned to one of three groups: aerobic control, I/R alone, and IPreC. Lactate dehydrogenase leakage, as a marker of cell injury, and cell viability were measured. The basal redox status was determined in samples from 90 patients.The response to I/R varied widely. Myocardium from patients with aortic valve disease was the most susceptible to injury whereas myocardium from dyslipidemia patients was the least susceptible. Tissue from females was better protected than tissue from males. Myocardium from patients with mitral valve disease was the least responsive to IPreC. The basal redox status was altered in the myocardium from patients with mitral and aortic valve disease.ConclusionsThe response of the myocardium to I/R and IPreC is highly variable and influenced by the underlying cardiac pathology, dyslipidemia, sex, and the basal redox status. These results should be taken into account in the design of future clinical studies on the prevention of I/R injury and protection.

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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.