Coronary Endothelial Injury After Cardiopulmonary Bypass and Ischemic Cardioplegia Is Mediated by Oxygen-Derived Free Radicals

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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 190μm 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 crystalloid cardioplegia (-28±10%o). Bradykinin elicited near complete relaxation of control vessels (96±3%, P<.05), whereas it caused considerably less relaxation after cardioplegia (33±9%,o). 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.


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.

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