ALLOPURINOL IMPROVES MYOCARDIAL REPERFUSION INJURY IN A XANTHINE OXIDASE-FREE MODEL

The ability of allopurinol to protect against reperfusion injury in th e heart has usually been attributed to its xanthine oxidase (XO)-inhib iting properties. Human myocardium however, has exhibited low levels o f XO activity. To investigate the effects of allopurinol in an XO-free model and determine whether pretreatment is necessary, 12 domestic pi gs (15 kg to 20 kg) underwent occlusion of the left circumflex for 8 m inutes followed by reperfusion for 4 hours. One group received allopur inol infusion (5 mg/kg IV) at occlusion over 45 minutes and a control group (n = 6) received a saline infusion (same volume). Left ventricul ar and aortic pressure, electrocardiograms, and regional wall motion ( sonomlcrometry) were monitored throughout the process. Regional blood flow (microspheres) were obtained before, during, and 5, 10, and 30 mi nutes after Ischemia. Occlusion decreased transmural flow at the midpa pillary level by 75% (0.28 versus 1.10 mL/minute/g). The allopurinol-t reated group exhibited a mild, generalized hyperemia at 5 minutes (isc hemic zone: 1.44 versus 1.10 mL/min/g, which returned to control level s at 10 and 30 minutes. In contrast, the control group was associated with only 80% restoration of resting blood flow at 5 minutes (0.84 ver sus 1.10 mL/min/g), which stabilized at 63% of control levels at 10 an d 30 minutes, When evaluated for the propensity of arrhythmias using a n arbitrary arrhythmia score, the allopurinol group demonstrated no my ocardial ectopy when compared with the focal ectopy routinely encounte red in the control group at all time intervals. Since pigs have no det ectable levels of XO activity allopurinol must exert its protectant ef fect during myocardial reperfusion by an alternative mechanism. Becaus e protection was evident without pretreatment, beneficial effects may not necessarily be the result of allopurinol degradation products; the refore, pretreatment with allopurinol may not be necessary. These resu lts are clinically important when considering the use of allopurinol i n an emergent coronary angioplasty or coronary artery bypass grafting.