Abstract

The efficacy of oxygen radical scavengers in preservation of left ventricular (LV) function after prolonged hypothermic global ischemia was investigated in a model of orthotopic cardiac transplantation in sheep. Group 1 hearts (N = 8) received hypothermic crystalloid cardioplegic solution, and were harvested and stored at 4°C in balanced electrolyte solution for six hours prior to transplantation. Group 2 (N = 9) received identical treatment with the addition of 30,000 units of superoxide dismutase to the cardioplegic solution and the administration of 60,000 units of superoxide dismutase coincident with reperfusion. All animals were weaned from cardiopulmonary bypass. Preischemic and postischemic LV function was determined using sonomicrometry and a micro-manometer-tipped LV catheter. Coronary blood flow was determined using standard microsphere techniques, and platelet deposition was assayed with autologous platelets labeled with indium 111. Lipid peroxidation products were measured using thiobarbituric acid assay. LV performance was significantly better ( p < .05) in Group 2 hearts when assessed by the slope of the end-systolic pressure-volume relationship and the stroke work versus end-diastolic volume relationship. There was better preservation of endocardial blood flow in the group receiving superoxide dismutase compared with controls ( p < .05). Platelet deposition, as determined by the tissue to blood ratio of scintigraphic counts, was greater ( p < .05) in controls compared with the group receiving superoxide dismutase. In addition, thiobarbituric acid reactive species were significantly less ( p < .05) in Group 2 versus Group 1 hearts. In the setting of prolonged (six hours) hypothermic global ischemia and reperfusion, free radical scavengers promote better return of LV function, improved endocardial blood flow, less platelet deposition, and fewer lipid peroxidation products. These results suggest that free radical scavengers may prove beneficial in prolonging viable hypothermic ischemic time for cardiac transplantation.

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