The effects of metoprolol and dazmegrel, alone and in combination, on arrhythmias induced by coronary artery occlusion in conscious rats

The effects of metoprolol and the thromboxane synthetase inhibitor dazmegrel, alone and in combination, were examined in a model of coronary artery occlusion in conscious rats. In a dose (2 mg kg-1), intravenously, that resulted in a marked bradycardia (of 50-80 beats min -1) metoprolol did not influence the incidence or severity of the ventricular arrhythmias that occur in the first 20 min following occlusion, nor did it improve survival (assessed at both 20 min and 16 h). In a dose (5 mg kg-1), intravenously, that in another conscious rat model involving tissue hypoperfusion inhibited thromboxane production, dazmegrel also did not modify ischaemic arrhythmias or survival. In contrast, metoprolol and dazmegrel (2 mg kg-1 and 5 mg kg-1 i.v.) when given together prior to coronary artery occlusion, produced a significant reduction in mortality both at 20 min and 16 h (e.g. from 60-75% in the control, metoprolol alone and dazmegrel alone groups and only 25% in the combined-treatment group). This was due to a decrease in the incidence of terminal ventricular fibrillation. The results suggest that a combination of beta-adrenoceptor blocking drug with a drug that inhibits thromboxane synthesis may offer more protection against ischaemia-induced ventricular fibrillation than either drug used alone. They suggest a role for both catecholamines and thromboxane in the genesis of ischaemia-induced ventricular fibrillation.