Failure of allopurinol and a spin trapping agent N-t-butyl-alpha-phenyl nitrone to modify significantly ischaemia and reperfusion-induced arrhythmias

Br J Pharmacol. 1987 May;91(1):49-59. doi: 10.1111/j.1476-5381.1987.tb08982.x.

Abstract

The possible role of free radicals in the genesis of occlusion and reperfusion-induced arrhythmias was studied by determining the effects of the xanthine oxidase inhibitor allopurinol (400 mg p.o. 24 h before experimentation +25 mg kg-1 i.v.) and the free radical scavenger N-t-butyl-alpha-phenyl nitrone (PBN; 50 mg kg-1 i.v.) on these arrhythmias in chloralose anaesthetized greyhounds. Neither of the drugs had any major effects on haemodynamic variables, although allopurinol caused a significant increase in heart rate. The mean number of extrasystoles observed during ischaemia in dogs given allopurinol or PBN was not significantly different from those seen in controls. Further, the incidence of ventricular fibrillation during either occlusion or reperfusion was unchanged by either drug and there was thus no improvement in survival. These results suggest that, in this model of myocardial ischaemia and reperfusion, free radicals may not play a major role in the genesis of life-threatening arrhythmias.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / pharmacology*
  • Animals
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / physiopathology*
  • Arrhythmias, Cardiac / prevention & control
  • Blood Gas Analysis
  • Coronary Circulation / drug effects
  • Coronary Disease / complications
  • Coronary Disease / physiopathology*
  • Cyclic N-Oxides
  • Dogs
  • Female
  • Free Radicals
  • Hemodynamics / drug effects
  • Hydrogen-Ion Concentration
  • Lactates / blood
  • Male
  • Nitrogen Oxides / pharmacology*

Substances

  • Cyclic N-Oxides
  • Free Radicals
  • Lactates
  • Nitrogen Oxides
  • phenyl-N-tert-butylnitrone
  • Allopurinol