Free radicals and cardioplegia: allopurinol and oxypurinol reduce myocardial injury following ischemic arrest.
Oxygen-derived free radicals generated by xanthine oxidase may represent a major cause of myocardial injury during ischemia and reperfusion. We have used the isolated working rat heart model of cardiopulmonary bypass and ischemic arrest to assess whether allopurinol or oxypurinol, which should prevent free radical formation through their ability to inhibit xanthine oxidase, can improve postischemic myocardial recovery when the drugs are administered either chronically (pretreatment) or acutely (as an addition to the cardioplegic or reperfusion solution). With normothermic ischemic arrest, both drugs, when given either chronically or acutely, significantly improved postischemic recovery of function. However, under hypothermic conditions, allopurinol conferred no protection when given either as pretreatment or during reperfusion, but it was effective when added to the cardioplegic solution. When administered under the appropriate conditions, both allopurinol and oxypurinol enhanced the protective effect afforded by the St. Thomas' Hospital cardioplegic solution, possibly by inhibiting xanthine oxidase activity and preventing the formation of oxygen-derived free radicals.
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates; D002122:Calcium Chloride; D005609:Free Radicals; D006324:Heart Arrest, Induced; D008274:Magnesium; D008297:Male; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D010117:Oxypurinol / Q000494:pharmacology*; D011189:Potassium Chloride; D011292:Premedication; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D001639:Bicarbonates; D005609:Free Radicals; D011743:Pyrimidines; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D000493:Allopurinol; D011189:Potassium Chloride; D014969:Xanthine Oxidase; D010117:Oxypurinol; D008274:Magnesium; D002122:Calcium Chloride