HYPEROXIA CONFERS MYOCARDIAL PROTECTION IN MECHANICALLY VENTILATED RATS THROUGH THE GENERATION OF FREE RADICALS AND OPENING OF MITOCHONDRIAL ATP-SENSITIVE POTASSIUM CHANNELS

SUMMARY 1 One hour exposure to hyperoxia has been shown previously to limit a subsequent ischaemia–reperfusion injury in spontaneously breathing rats. We tested the cardioprotective effect of a shorter period of hyperoxia during mechanical ventilation and the possible contribution of reactive oxygen species (ROS) and mitochondrial ATP‐sensitive potassium (mitoKATP) channels. 2 Mechanically ventilated rats were exposed to normoxia (Fio2 = 0.3) or hyperoxia (Fio2 = 1.0) for 30 min and pH, Pco2, Po2, heart rate, airway and blood pressure were measured at baseline and after 30 min mechanical ventilation. Isolated hearts were subsequently subjected to 30 min ischaemia and 120 min reperfusion. Infarct size and left ventricular end‐diastolic pressure (LVEDP), developed pressure (LVDP) and coronary flow (CF) were measured. In order to investigate the role of ROS and KATP channels within the mechanism leading to cardioprotection, the free radical scavenger N‐acetylcysteine (NAC; 150 mg/kg) was infused in mechanically ventilated rats and the KATP channel blockers glibenclamide (200 mmol/L) or 5‐hydroxydecanoate (10 mmol/L) were infused in isolated hearts immediately before ischaemia. 3 No differences were detected in Pco2, pH, heart rate, airway and blood pressure between the groups. However, the Po2 in hyperoxic groups was significantly higher compared with that in normoxic groups (P