Single and combined myocardial pharmacodynamics of xamoterol, isoprenaline and g-strophanthin in the isolated rabbit heart.

The myocardial effects of g-strophanthin and the partial beta 1-adrenoceptor agonist xamoterol were compared to the effects of isoprenaline in the isolated spontaneously beating rabbit heart. Xamoterol and g-strophanthin both produced a distinct maximum increase in contractility as shown by the increase in isotonic contraction rate from 100 to 142% (pD2 7.51) and 151% (pD2 6.54), respectively, which was however less pronounced than the increase to 200% (pD2 7.81) caused by isoprenaline. The maximum chronotropic effect of xamoterol was moderate with a frequency increase from 100 to 128% (pD2 7.40) as was the increase in oxygen consumption to 130% (pD2 7.16), and no arrhythmias were seen. The positive inotropic range of g-strophanthin was very narrow (about 60-600 nM) and cardiac toxicity just overlapped and rapidly increased over this range. Xamoterol at a fixed concentration of 28 nM caused a rightwards shift of the isoprenaline concentration-response curves demonstrating the competitive beta 1-adrenoceptor blocking effect of the drug. G-strophanthin at a concentration of 268 nM acted additively with xamoterol with regard to maximum contractility and without causing any further increase in myocardial oxygen consumption except at the highest concentrations but there was a slightly increased nodal rhythm at xamoterol concentrations higher than about 20 nM.