We have investigated the possibility that
xanthine oxidase-linked
free radical production has a role in the genesis of arrhythmias during
ischemia and reperfusion. In this study, rats were treated with
allopurinol (20 mg/kg, orally, 24 hours before study, plus 20 mg/kg, iv, 15 minutes prior to study). Using an anesthetized open-chest preparation with either coronary artery occlusion for 30 minutes, or 5 minutes followed by 10 minutes reperfusion, we monitored and compared the rhythm disturbances in experimental vs. placebo-treated rats (n = 18 in each group).
Allopurinol treatment reduced the incidence of
ventricular tachycardia during
ischemia from 88% to 50% (P less than 0.05) and the number of premature ventricular complexes from 471 +/- 120 to 116 +/- 46 (P less than 0.02), but the treatment had no effect upon the incidence or duration of
ventricular fibrillation or upon mortality. In contrast, far more dramatic protection was observed during reperfusion after 5 minutes of
ischemia.
Allopurinol treatment reduced the incidence of
ventricular fibrillation from 67% to 11% (P less than 0.01), reduced the mean duration of fibrillation from 230 +/- 70 to 14 +/- 1 seconds (P less than 0.05), and reduced mortality by half (10/18 to 4/18), although this did not reach a level of statistical significance. In addition, the mean duration of
tachycardia was reduced from 83 +/- 26 to 38 +/- 8 seconds (P less than 0.05).
Allopurinol pretreatment thus affords some protection against
ischemia-induced arrhythmias, but a higher degree of protection against reperfusion-induced arrhythmias.
Allopurinol inhibits
xanthine oxidase activity, and, in turn, this inhibits
superoxide radical production.(ABSTRACT TRUNCATED AT 250 WORDS)