Coronary endothelial injury after cardiopulmonary bypass and ischemic cardioplegia is mediated by oxygen-derived free radicals.

BACKGROUND: Cardiopulmonary bypass and crystalloid cardioplegia may lead to endothelial dysfunction in the coronary microcirculation. The aim of the present study was to examine whether the alteration of endothelium-dependent microvascular responses may be related to the generation of oxygen-derived free radicals. METHODS AND
RESULTS: Pigs (30 kg) were heparinized and placed on cardiopulmonary bypass. The hearts were arrested for 1 hour with either plain hypothermic, hyperkalemic (25 mEq/L) crystalloid cardioplegic solution (n = 10) or crystalloid cardioplegic solution containing either deferoxamine (n = 8) or manganese superoxide dismutase (n = 6). Hearts were then reperfused for 1 hour while the pigs were separated from cardiopulmonary bypass. Noninstrumented pigs were used as controls (n = 8). Coronary microarteries (120 to 190 microns in diameter) were studied in vitro in a pressurized (40 mm Hg), no-flow state with videomicroscopy and electronic dimension analysis. After precontraction of microvessels, the endothelium-dependent and -independent agents were applied extraluminally. Serotonin caused a slight dilation of control vessels (percent dilation of acetylcholine-induced preconstriction at 10 mumol/L drug concentration, 5 +/- 8%; P < .05 versus crystalloid cardioplegia group) and a significant contractile response after crystalloid cardioplegia (-28 +/- 10%). Bradykinin elicited near complete relaxation of control vessels (96 +/- 3%, P < .05), whereas it caused considerably less relaxation after cardioplegia (33 +/- 9%). The addition of either deferoxamine or superoxide dismutase to the cardioplegic solution significantly (but not completely) preserved vasomotor responses of coronary microvessels to serotonin (9 +/- 6% and 11 +/- 4%, respectively; P < .05) or bradykinin (72 +/- 4% and 87 +/- 3%, respectively; P < .05). Endothelium-independent relaxations of vessels in response to sodium nitroprusside were similar in all groups.
CONCLUSIONS: Either the hydroxyl radical synthesis inhibitor deferoxamine or manganese superoxide dismutase preserves endothelium-dependent relaxation during crystalloid cardioplegia-reperfusion. Therefore, ischemic cardioplegia-reperfusion-induced endothelial dysfunction is at least partially mediated by the generation of oxygen-derived free radicals.