Background: Ischemic heart disease is the major cause of death in developed countries and infarct size is the major determinant of prognosis. Ischemic postconditioning (IPostC), a sequence of short reperfusion-ischemia episodes after a prolonged ischemic period, has been proposed as a useful approach to reduce infarct size in all species, including humans, but its clinical utility remains unclear.
Purpose: The aim of this study was to investigate the efficacy of IPostC in protecting the human myocardium and the role played by the protocol applied and by the clinical conditions.
Methods: The right atrial appendage was obtained from patients undergoing elective cardiac surgery. The muscles were subjected to 90min of simulated ischemia followed by 120 min of reoxygenation and then randomized to different protocols of IPostC. In study 1, the role of the time of ischemia (30, 60, 90 and 120sec) for IPostC was investigated, whereas in studies 2 and 3 the importance of the number of cycles (1, 2, 3 and 4 cycles) using two different total times of ischemia (60 and 120sec) was examined. Muscles were also subjected to ischemic preconditioning (IPreC), the most effective protocol in this in vitro model. The released of lactic dehidrogenase acid (LDH) into the media during the reoxygenation period and the assessment of tetrazolium bromide (MTT) in muscle at the end of the experimental period were determined as index of tissue injury and cell viability, respectively.
Results: IPostC increased the LDH and decreased the MTT mean values from those of control (ischemia/reoxygenation alone) in all the studies independently of the protocol investigated, varying from 25% to 150%. Despite this, between 20 and 40% of the cases showed better values than the respective control, with 90 and 120sec of ischemia and 1 cycle of ischemia being the most protective. Conditions such as diabetes and mitral and tricuspid valve disease, and treatments such as statins and steroids resulted in further IPostC-induced injury. In contrast, IPreC significantly improved LDH and MTT mean values with 77% of the cases exhibiting benefit.
Conclusions: Overall IPostC increases myocardial injury and exhibits some degree of cardioprotection in only 20-40% of the cases. The efficacy depends on the protocol used, with a period of 120sec of total ischemia and 1 cycle of ischemia being the most protective. In addition, conditions like diabetes and mitral and tricuspid valve disease and also treatment with statins and steroids result in reduced cardioprotection. These results question the clinical utility of IPostC.