Arrhythmias induced by myocardial ischaemia-reperfusion are sensitive to ionotropic excitatory amino acid receptor antagonists

We have investigated the effects of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801), a non-competitive N-methyl-D-aspartate (NMDA) ionotropic excitatory amino acid receptor antagonist, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA ionotropic excitatory amino acid receptor antagonist, ketamine and memantine, NMDA receptor channel blockers, on ventricular arrhythmias induced by myocardial ischaemia and myocardial ischaemia-reperfusion. Coronary artery occlusion caused 100 +/- 2% ventricular tachycardia, in saline treated group, and 60 +/- 3% ventricular fibrillation. 66 +/- 6% of the animals recovered from ventricular fibrillation, while in 34 +/- 4% of animals the ventricular fibrillation caused mortality. The incidence of ventricular tachycardia, ventricular fibrillation and mortality was not modified by treatment of rats with MK801 (0.3 mg/kg i.v.), CNQX (1 mg/kg i.v.), ketamine (10 mg/kg) and memantine (1.5 mg/kg), injected 5 min prior to occlusion. Reperfusion caused severe arrhythmias which started within 5 +/- 2, a. For instance, in the saline treated group, the incidence of ventricular tachycardia was 100 +/- 5%, while ventricular fibrillation occurred in 87 +/- 3% of the animals and lasted 90 +/- 12 s. The mortality was 62 +/- 6%. The incidence of ventricular tachycardia, ventricular fibrillation and mortality induced by reperfusion was greatly (P < 0.01) reduced in animals treated with MK801 (0.3 mg/kg; i.v.), CNQX (1 mg/kg i.v.), ketamine (10 mg/kg) and memantine (1.5 mg/kg), injected 5 min prior to occlusion. Therefore, reperfusion-induced arrhythmias, but not ischaemia-induced arrhythmias, are sensitive to NMDA/non-NMDA ionotropic excitatory amino acid receptor antagonists. (C) 1999 Elsevier Science B.V. All rights reserved.