Effects of aspirin and indomethacin on ventricular arrhythmias- comparative study

The effects of aspirin and indomethacin on the ventricular arrhythmias produced by ligation [ischaemia] and unligation [reperfusion] of the circumflex branch of the left coronary vessel were evaluated in fifty male rabbits weighing 1.5 - 2 kg. Pretreatment of animals with aspirin [50 mg/kg i/v] suppressed all arrhythmias during ischaemia. Low dose of aspirin [12.5 mg/kg i/v] produced no mortality. Indomethacin [2.5 mg/kg] was unable to control ischaemia and reperfusion-induced ventricular arrhythamis. However, higher doses of indomethacin [50 mg/kg] suppessed ischaemia-induced arrhythamias to some extent but the mortality rate was increased [37%]. Fragment of ventricular fibrillation was zero during ischaemia after treatment with aspirin and indomethacin but reperfusion-induced ventricular fibrillation was not controlled by any of these drugs. Aspirin [12.5 mg/kg, 50 mg/kg] and indomethacin [2.5 mg/kg] significantly suppressed ischaemia - induced tachyarrhythmias while reperfusion induced tachyarrhythmias were suppressed only by aspirin. There was no significant effect on the mean arterial pressure after these drug treatments

effects of nonsteroidal anti-inflammatory drugs [NSAIDs] on the spontaneously beating isolated auricles of the rabbit heart

The effects of NSAIDs [aspirin and indomethacin] on the isolated auricles of the rabbit heart were studied by observing the effects of these drugs on automaticity, excitability and contractility of the auricles. Aspirin [25, 50, 100 uM] produced concentration dependent depression in the automaticity of the SA node while indomethacin [10 uM, 25 uM] has stimulant effects and 50 uM produced depressant action. Only low concentration of indomethacin [10 uM] produced significant effect. Aspirin [25, 50, 100 uM] and indomethacin [50 uM] have significant depressant effects on the excitability of the auricles. Aspirin [100 uM] has supporessant effects [p<0.05] on the normal contractility while the adrenaline stimulated contractility is not suppressed by aspirin and indomethacin significantly. The results obtained in this study with aspirin and indomethacin on chronotropicity and inotropicity of the rabbit atria have been discussed in the light of experimental work done by the workers regarding conventional antiarrhythmic drugs

Combined effects of aspirin and propranolol on the tachyarrhythmias

We have observed the effects of aspirin and propranolol on the adrenaline-stimulated activity of the isolated auricles of the rabbit heart as well as on the ischaemia-induced and reperfusion-induced activity of the pentobarbitone-anesthetized rabbit heart. Aspirin [25-100 uM] has suppressant effects on the adrenaline-stimulated tachyarrhythmias of the isolated auricles. Aspirin [12.5 mg/kg] also suppresses ischaemia-induced and reperfusion induced tachycardia. These effects of aspirin are similar to propranolol [5x10[-8] M - 3x10[-6] M for isolated auricles and 0.02 mg/kg for pentobarbitone-anesthetized rabbits]. Aspirin-propranolol combination showed no significant effects on the isolated auricles of the rabbit heart while ischaemia-induced and reperfusion induced tachyarrhythmias are significantly suppressed. Therefore, we conclude that aspirin and propranolol alone have marked suppressant effects on the adrenaline-stimulated activity of isolated auricles while aspirin-propranolol combination has no such effect. On the other hand, low dose of aspirin and propranolol have significant suppressant effects on the ischaemia-induced and reperfusion-induced tachyarrhythmias and the combination of aspirin and propranolol showed potentiation in this type of tachyarrhythmias