Continuous Normobaric Hypoxia Improved Cardiac Bioenergetics after Ischemia/Reperfusion: Role of Opioid Receptors

We analyzed the role of opioid receptors in the conditioning effect of continuous normobaric hypoxia on bioenergetics of the heart subjected to ischemia/reperfusion injury. Male Wistar rats were adapted to a 21-day continuous normobaric hypoxia (12% pO(2)). Then, the hearts were isolated and subjected to 45-min total ischemia followed by 30-min reperfusion. Damage to the myocardium was assessed by activity of creatine phosphokinase in the perfusate. Experiments on isolated mitochondria showed that ischemia/reperfusion injury decreased the respiration rate in state 3 (V-3), the ratio of added ADP and oxygen consumption in respiration state 3 (ADP/O ratio), the mitochondrial potential across the inner membrane (Delta psi), and Ca2+ binding capacity of mitochondria. In addition, ischemia/reperfusion injury decreased myocardial ATP. Preventive continuous normobaric hypoxia pronouncedly moderated these adverse effects of reperfusion. It was found that its protective effects were related to activation of cardiac mu- and delta(2)-opioid receptors.