Mechanism of defective oxygen extraction following global ischemia

Prolonged global ischemia has been shown to result in a defect in oxygen extraction (O₂E) which is not related to postischemic changes in coronary blood flow or ventricular contractility. Possible explanations for this defect include either (1) decreased O₂ delivery due to diffusion barriers, arterial-venous (A-V) shunting, or myocardial flow maldistribution, or (2) an impaired cellular ability to utilize delivered O₂. Studies were carried out in 24 isolated perfused feline hearts divided into three equal groups. Groups I and II were subjected to 60 min of 37°C ischemia; Group III was protected with hypothermia (27°C) and potassium cardioplegia during the 60 min of ischemia. Group II underwent hyperosmolar (340 mOsm) reperfusion with mannitol to improve subendocardial perfusion; Groups I and III had isosmolar postischemic reperfusion. In addition to O₂E determinations, myocardial O₂ (P_mO₂) was monitored continuously by mass spectrometry. Radioactive microspheres were used to measure both A-V shunting and endo/epi flow ratios. Postischemic O₂E was depressed in Group I (70 ± 5% of control) and Group II (70 ± 4% of control) but was unaltered in Group III (105 ± 8% of control). This impairment of O₂E was not associated with increased A-V shunting. P_mO₂ was not different among the three groups excluding diffusion barriers as a likely explanation. Improving transmural myocardial perfusion in Group II did not result in improvement in postischemic O₂E making flow maldistribution an unlikely cause of this defect. The mechanism of defective postischemic O₂E, therefore, must be an impaired capacity for utilization of delivered O₂ at the cellular level.