Inotropic, chronotropic and dromotropic effects of prenalterol, a new cardiostimulant drug

Prenalterol (H 133/22) is an adrenergic beta-receptor stimulator which unlike isoproterenol is both orally active and has a long duration of action. The inotropic, chronotropic and dromotropic effects of prenalterol were investigated in pentobarbital anaesthetized dogs. Prenalterol was found to increase left ventricular maximum dP/dt in a dose-dependent manner up to a dose level of 50 micrograms/kg. Additional doses resulted in only small further increases in cardiac contractility. Electrophysiological studies were done to compare the effects of prenalterol and isoproterenol on sinus node and ventricular pacemaker function. Complete AV block was produced by electrocauterization of the His bundle. Prenalterol accelerated both ventricular and sinus node pacemakers at doses up to 50 micrograms/kg. The increase in ventricular rate was greater than the increase in sinus rate following supramaximal inotropic doses of prenalterol yet no ventricular extrasystoles were ever observed. Similar acceleration of the ventricular and sinus node pacemakers were observed by infusion of isoproterenol. Prenalterol and isoproterenol accelerated AV nodal conduction and ventricular conduction but had little effect upon His-Purkinje conduction. Sinus node reset time was abbreviated as was the functional and effective refractory periods of the atrium and AV nodes.