Mechanically induced ventricular extrasystoles in the isolated perfused guinea-pig heart. A model to study cardiac arrhythmia and to differentiate antiarrhythmic drugs.

Pressure pulses applied to an isolated perfused guinea-pig heart via underwater hydrodynamic pressure waves during early diastole induce ventricular extrasystoles (VES). Intensity of pulse pressure and number of VES in relation to number of stimuli show a narrow and reproducible relation following a sigmoid function. Thus we were able to establish a pressure dose-response function between hydrodynamic peak pressure and percentage of VES-responses to mechanical stimulation. In overriding the natural heart rate a ventricular rhythm can be maintained for several hours. In the hypoxic or anoxic heart repetitive automatism can be induced by pulse pressure stimulus. In severe ischemia ventricular fibrillation may occur. In this model differentiation between various classes of antiarrhythmic drugs seems possible in setting up pressure dose-response curves for different concentrations of these drugs. The inhibition of VES is limited to class I antiarrhythmic drugs (quinidine, lidocaine) while specific Ca-antagonists (class IV) are ineffective, thus showing that induction of VES is mediated by a Na channel-dependent process. Preliminary data show that these results can be extended to in situ experiments using an external mechanical stimulator.