CORONARY ENDOTHELIAL INJURY AFTER CARDIOPULMONARY BYPASS AND ISCHEMICCARDIOPLEGIA IS MEDIATED BY OXYGEN-DERIVED FREE-RADICALS

Background. Cardiopulmonary bypass and crystalloid cardioplegia may le ad to endothelial dysfunction in the coronary microcirculation. The ai m of the present study was to examine whether the alteration of endoth elium-dependent microvascular responses may be related to the generati on 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 m Eq/L) crystalloid cardioplegic solution (n=10) or crystalloid cardiopl egic solution containing either deferoxamine (n=8) or manganese supero xide 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 mum i n diameter) were studied in vitro in a pressurized (40 mm Hg), no-flow state with videomicroscopy and electronic dimension analysis. After p recontraction of microvessels, the endothelium-dependent and -independ ent agents were applied extraluminally. Serotonin caused a slight dila tion of control vessels (percent dilation of acetylcholine-induced pre constriction at 10 mumol/L drug concentration, 5+/-8%; P<.05 versus cr ystalloid cardioplegia group) and a significant contractile response a fter crystalloid cardioplegia (-28+/-10%). Bradykinin elicited near co mplete relaxation of control vessels (96+/-3%, P<.05), whereas it caus ed considerably less relaxation after cardioplegia (33+/-9%). The addi tion of either deferoxamine or superoxide dismutase to the cardioplegi c solution significantly (but not completely) preserved vasomotor resp onses of coronary microvessels to serotonin (9+/-6% and 11+/-4%, respe ctively; P<.05) or bradykinin (72+/-4% and 87+/-3%, respectively; P<.0 5). Endothelium-independent relaxations of vessels in response to sodi um nitroprusside were similar in all groups. Conclusions. Either the h ydroxyl radical synthesis inhibitor deferoxamine or manganese superoxi de dismutase preserves endothelium-dependent relaxation during crystal loid cardioplegia-reperfusion. Therefore, ischemic cardioplegia-reperf usion-induced endothelial dysfunction is at least partially mediated b y the generation of oxygen-derived free radicals.