Postischemic reperfusion injury can be attenuated by oxygen tension control

Oxygen-derived free radicals cause cytotoxic damage during reperfusion afte r a period of ischemia and the production of these free radicals may be pro portionate to oxygen tension.(PO2). The present study tested the hypothesis that oxidative damage may be limited by maintaining a more physiologic PO2 following ischemia. An experimental study in Wistar rats were mounted on a Langendorff apparatus was conducted to estimate baseline aortic flow (AF), coronary flow (CF), cardiac output (CO), systolic pressure (SP), heart rat e (HR), and the rate-pressure product (RPP: HRxSP). The hearts were divided into 3 groups (n=7, hearts/group): group 1, hypoxic (PO2=300+/-50 mmHg) re perfusion; group 2, middleoxic (PO2=500+/-50 mmHg) reperfusion; and group 3 , hyperoxic (PO2=700+/- 50 mmHg) reperfusion. Following 30 min of warm isch emia, hearts in all groups were reperfused at each oxygen pressure. The rec overy of cardiac function of each heart was measured at the end of reperfus ion. Concentrations of lactate (LAC), lactate dehydrogenase (LDH), and crea tine kinase (CK) in the coronary perfusate during reperfusion were measured . The recovery rate of CO, SP, and RPP in group 2 were all significantly be tter than in the other 2 groups. CK leakage in group 2 was significantly lo wer than in group 3. A clinical study was also conducted during elective co ronary artery bypass grafts in 16 consecutive patients who underwent either hyperoxic (n=8, PO2=450-550 mmHg) or more physiologic (n=8, PO2=200-250 mm Hg) cardiopulmonary bypass after aortic unclamping. The clinical study asse ssed CK-MB, LDH, LAG, and malondialdehyde (MDA) in patient blood prior to s tarting the surgical procedure and at 30 min and 3, 9, and 21 h after uncla mping. Cardiac index (CI), central venous pressure, pulmonary capillary wed ge pressure, systolic arterial pressure, and the dose of cathecholamines we re also measured. Although no significant differences were present in the d ose of cathecholamines, the CI in the more physiologic oxygen tension group was significantly higher than in the hyperoxic group at 3 and 6 h after un clamping. The levels of MDA in the more physiologic PO2 group was significa ntly lower at 30 min after aortic unclamping than in the hyperoxic group. T he present results suggest that in the experimental as well as in the clini cal study, high PO2 leads to myocardial reperfusion damage; however, mainta ining a more physiologic PO2 during reperfusion following ischemia may atte nuate reperfusion injury.