Effects of methoxamine and phenylephrine on left ventricular contractility in rabbits

Abstract

The end-systolic pressure-volume relation is employed to evaluate left ventricular contractility. In clinical studies, pharmacologic vasoconstriction is used to increase left ventricular systolic pressure to assess pressure-volume relations. However, the effect of vasoconstrictors on the ventricular contractile state is not well characterized. The effects of methoxamine and phenylephrine on systemic arterial pressure and left ventricular contractility in rabbits were studied with three protocols.In protocol 1, anesthetized rabbits (n = 10) were injected with incremental doses of methoxamine and phenylephrine intravenously. Methoxamine (4 mg) increased the mean arterial pressure by 50 ± 12% (mean + SE) (n = 5, p = 0.001). Phenylephrine (0.2 mg) increased mean arterial pressure by 82 ± 14% (n = 5, p = 0.004). In protocol 2, isolated blood-perfused hearts were injected with incremental doses of these drugs in the ascending aorta in amounts approximately equal to the concentrations injected in the intact rabbits. Methoxamine (2 mg) reduced isovolumic peak systolic left ventricular pressure by 43 ± 9% (n = 7, p = 0.003), whereas phenylephrine (0.1 mg) increased the isovolumic pressure by 24 ± 9% (n = 7, p < 0.05). These responses indicated an enhanced contractile state with phenylephrine and a reduced contractile state with methoxamine. Pretreatment with propranolol blunted the effect of phenylephrine on isovolumic pressure (n = 6, p < 0.02).In protocol 3, cross-circulation experiments allowed study of the effect of these drugs on isovolumic left ventricular pressure in the isolated heart and simultaneously on the systemic arterial pressure in the intact anesthetized rabbit (support rabbit). Methoxamine decreased isovolumic left ventricular pressure at infusion rates that increased mean arterial pressure in the support rabbit. With phenylephrine, both the left ventricular isovolumic pressure and the mean arterial pressure increased.Thus, in the isolated supported heart, phenylephrine increased left ventricular contractility at doses that produced peripheral vasoconstriction in the intact rabbit. Conversely, methoxamine reduced ventricular contractility in the isolated heart at doses that produced peripheral vasoconstriction in the intact rabbit. The isolated hearts had variable susceptibility to the depressant effect of methoxamine. These results demonstrated the allowable range for valid results and the limitations of using pharmacologic vasoconstricting agents to manipulate arterial pressure afterload when assessing left ventricular contractility in this model and possibly in humans.