Arrhythmias and infarction in the ischemic pig heart are not mediated by xanthine oxidase-derived free oxygen radicals.
Xanthine oxidase activities of pig myocardium and blood during and following myocardial ischemia were measured using HPLC, and electrochemical detection of hypoxanthine, xanthine and uric acid. Myocardial ischemia was produced by occluding the anterior descending coronary artery two-thirds of the way from its origin. There was no accumulation of either xanthine or urate in the ischemic pig myocardium during occlusion periods of 90 min, but there was a substantial accumulation of hypoxanthine. Similarly, there was no increase in myocardial xanthine or urate during the 30 min reperfusion following coronary artery occlusion periods of 15, 30, 60 or 90 min. Following in vitro incubation at pH 8 of myocardial homogenates or blood with either hypoxanthine or xanthine and NAD, no urate production was detectable. In contrast, significant amounts of xanthine and/or urate were produced, following addition of xanthine oxidase to the reaction mixtures. Additional in vitro experiments showed that the following pig tissues were lacking xanthine oxidase activity: left and right atrial appendage, left and right ventricle, interventricular septum, anterior descending and circumflex coronary arteries, ascending aorta, lung, and blood. Large amounts of xanthine oxidase (9.3 +/- 1.8 SEM mU/g wet weight, n = 7) were found in pig liver. In the ischemic pig heart, transmural infarction developed within 60 min of ischemia. Ventricular arrhythmias and fibrillation occurred most frequently within 45 min of ischemia and within seconds after reperfusion. These results showed that the pig heart and blood were xanthine oxidase deficient, suggesting that xanthine oxidase-derived free oxygen radicals were not involved in the cytotoxic and arrhythmogenic effects brought about by myocardial ischemia and/or reperfusion in the pig.
Max Planck Institute for Physiological and Clinical Research, Bad Nauheim, FRG.
T
T
Podzuweit
W
W
Braun
A
A
Müller
W
W
Schaper
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism*; D005609:Free Radicals; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D013552:Swine; D014969:Xanthine Oxidase / Q000378:metabolism*
D005609:Free Radicals; D014969:Xanthine Oxidase; D010100:Oxygen