Free radicals and cardioplegia: the absence of an additive effect with allopurinol pretreatment and the use of antioxidant enzymes in the rat.

The isolated perfused working rat heart model of cardiopulmonary bypass was used to assess whether (a) allopurinol pretreatment enhances resistance to normothermic (30 min) or hypothermic (4 h) ischemia; (b) addition of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) to cardioplegic and/or reperfusion solutions are protective; (c) any protective effects are additive. With normothermic ischemia, allopurinol pretreatment improved recovery of aortic flow from its control value of 25 +/- 3% to 48 +/- 6% (P less than 0.05). Similarly, SOD plus CAT used during both ischemia and reperfusion improved recovery of aortic flow from a control value of 28 +/- 4% to 48 +/- 6% (P less than 0.05). However, various combinations of the two types of intervention afforded no additive protection. Under hypothermic (21 degrees C) conditions, allopurinol pretreatment was not effective, whereas SOD and CAT added during ischemia and reperfusion improved recovery of aortic flow from its control value of 53 +/- 4% to 69 +/- 5% (P less than 0.05). This value was similar to allopurinol pretreatment and SOD plus CAT added during ischemia and reperfusion (69 +/- 6%: P less than 0.05). These results provide further evidence that reperfusion-induced free radical formation may adversely affect postischemic recovery of function. The absence of an additive effect suggests a common mechanism of action, which is likely to involve the free radical-generating enzyme xanthine oxidase; however, other mechanisms may exist. Our results further support the use of antifree radical intervention in conjunction with cardioplegia to protect the heart during ischemia and reperfusion.