Effect of Allopurinol on Myocardial Protection in the Isolating Working Heart

Kim, Sung Koo

Abstract

BACKGROUND
Oxygen free radicals may play important role in coronary reperfusion resulting in cell death or dysfunction, and they believed that one specific mechanism for producing oxygen free radicals in myocardium is the xanthine oxidase system. Allopurinol, inhibitor of xanthine oxidase system, may limit myocardial dysfunction and injury produced by oxygen free radicals during coronary reperfusion.
METHODS
Thirty isolated rabbit hearts undertook the retrograde nonworking perfusion for 15 minutes and followed by 15 minutes of working mode. After measurement of the hemodynamic values as baseline, all heart were arrested with cold cardioplegic solution for 60 minutes. Hearts were then revived with 15 minutes period of nonworking reperfusion, followed by 30 minutes of working reperfusion. The hemodynamic values were measured again at 20 minute of working period and expressed as percent of baseline values. Oxygen content of arterial perfusate and coronary effluent were measured and leakage of creatine kinase was measured from coronary effluent for 15 minutes of nonworking reperfusion. Wet and dry weight of the heart were obtained to determine for tissue water and water content. Animals were randomized as followings ; control(n=10), allopurinol PO(n=10, 100mg/kg before 24hr.), allopurinol IV(n=10, 10mg/kg before 1 hr.)
RESULTS
1) There were no significant differences in recovery of aortic pressure and heart rate between 3 groups. But there were significant differences in percent recovery of aortic flow, coronary flow, cardiac output and stroke volume between control group and allopurinol groups. 2) The leakage of creatine kinase following ischemic arrest was significantly lower in the allopurinol groups than the control group(control : 36.8+/-6.2IU, PO:19.7+/-3.1IU, IV : 22.2+/-4.6IU, p<0.001). 3) The allopurinol groups were significantly increased in oxygen extraction and oxygen consumption compared with the control((p<0.002, p<0.004)). 4) The tissue water and water content were significantly diminished in the allopurinol groups compared with the control group(p<0.003, p<0.001). 5) The electron micrograph showed more considerable structural damages of myocardial cell in the control group than the allopurinol groups.
CONCLUSION
It is suggested from the results that allopurinol, inhibitor of xanthine oxidase, plays a inhibiting role in the production of oxygen free radicals, and improves myocardial protection during global ischemia and reperfusion in the isolating working rabbit heart model.