SUPPRESSION OF REPERFUSION-INDUCED ARRHYTHMIAS WITH COMBINED ADMINISTRATION OF 5-HT2 AND THROMBOXANE A(2) ANTAGONISTS

1 The effects of the 5-HT2 antagonist, ICI 170,809 and the thromboxane A(2) antagonist, ICI 192,605, given alone and in combination (n = 12 per group), were examined in anaesthetized rats. Haemodynamics and arr hythmias induced by permanent coronary artery occlusion or by reperfus ion after 5 min of ischaemia were monitored. 2 In a study on reperfusi on-induced arrhythmias, the only significant effect of ICI 170,809 (1 mg kg(-1), i.v.) was a reduction in the number of ventricular prematur e beats (VPBs). ICI 192,605 (1 mg kg(-1) min(-1), i.v.) did not alter reperfusion-induced arrhythmias. However, in combination, when compare d with controls, these drugs caused significant reductions in the inci dence of ventricular tachycardia (VT), 100% to 58%; ventricular fibril lation (VF), 92% to 33%; and the mortality due to sustained VF, 67% to 17%. There was also a significant reduction in the number of VPBs fol lowing reperfusion. 3 In a second study with lower doses of drugs, ICI 170,809 (0.3 mg kg(-1)) and ICI 192,605 (0.3 mg kg(-1) min(-1)) had n o significant effects on reperfusion-induced arrhythmias either alone or in combination. 4 A third study examined the effects of the higher doses of the drugs on ischaemia-induced arrhythmias. Neither drug alon e, nor in combination, altered the incidence of ischaemia-induced VT, VF, the mortality, or the number of VPBs. 5 These results indicate tha t, in contrast to the administration of either drug alone, combined ad ministration of a 5-HT2 antagonist and a thromboxane A(2) antagonist c aused marked suppression of reperfusion-induced but not ischaemia-indu ced arrhythmias.