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


METHODS
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.


METHODS
Seven mongrel dogs of either sex, weighing 14-24 kg, were studied under sodium pentobarbitone anaesthesia.


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 intracardiac 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.
Mortensen
E
E
Department of Medical Physiology, University of Tromsø, Norway.
Tande
P M
PM
Kløw
N E
NE
Platou
E S
ES
Refsum
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001340:Autonomic Nerve Block; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D013997:Time Factors; D016276:Ventricular Function / Q000502:physiology
D002316:Cardiotonic Agents; D010879:Piperazines; C046261:DPI 201-106