Positive inotropy linked with class III antiarrhythmic action: electrophysiological effects of the cardiotonic agent DPI 201-106 in the dog heart in vivo

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Abstract
Study objective – The aim was to investigate whether the positive inotrope DPI 201-106 prolongs ventricular monophasic action potential duration and refractoriness in vivo without affecting conduction, thus possessing class III antiarrhythmic characteristics in vivo. Design – Electrophysiological and haemodynamic effects of DPI 201-106 (0.5, 1.0, and 2.0 mg·kg−1 intravenously) were studied at spontaneous heart rate and at three different paced cycle lengths (353, 300, and 261 ms). The following were recorded: monophasic action potentials from right ventricular endocardium; intracardiac conduction times by His bundle electrocardiography; refractoriness by programmed electrical stimulation; and left ventricular (LV) pressures. Subjects – Seven mongrel dogs of either sex, weighing 14-24 kg, were studied under sodium pentobarbitone anaesthesia. Measurements and main results – DPI 201-106 prolonged ventricular monophasic action potential duration and refractoriness dose dependently and most effectively at long cycle lengths, with no effect on intracardiic conduction times. DPI 201-106 increased LV dP/dtmax, while LV systolic and end diastolic pressures were unchanged both during spontaneous and paced heart rate. DPI 201-106 decreased spontaneous heart rate. Conclusions – Prolonged monophasic action potential duration and increased refractoriness, with no effect on conduction, indicate class III antiarrhythmic action of DPI 201-106 in vivo.