Myocardial responses to alpha-adrenoceptor stimulation with methoxamine hydrochloride in lambs

This study was undertaken to evaluate the effects of methoxamine on left ventricular performance, coronary blood flow (CBF), and myocardial oxygen consumption (MVO2) in lambs. Measurement of maximum rate of rise of left ventricular pressure (LV dP/dtmax), left ventricular end-diastolic pressure (LVEDP), CBF, and MVO2 were made in nine lambs using a hemodynamically controlled preparation. The lambs were given atropine sulfate (1 mg), tetraethylammonium chloride (100 mg), and practolol (4 mg/kg) to provide parasympathetic, ganglionic, and beta-adrenergic blockades. Aortic pressure and blood flow and heart rate were held constant in each lamb. Dose-related increases in LV dP/dtmax and decreases in LVEDP were observed after progressively larger doses of methoxamine ranging from 0.4 to 6.0 mg/kg were given. These positive inotropic responses were eliminated by giving phentolamine (2 mg/kg). CBF, myocardial O2 extraction, and MVO2 did not change significantly. A positive inotropic action of methoxamine was also demonstrated in five additional animals by obtaining ventricular function curves. Initially the mean stroke volume at LVEDP 10 cmH2O (SV10) was 4.11 +/- 0.16 (SE) ml. This value increased to 5.09 +/- 0.28 ml after methoxamine (P less than 0.01). After phentolamine, SV 10 fell to 4.37 +/- 0.08 ml (P less than 0.05). These observations support the hypothesis that alpha-adrenergic receptors are present and mediate a substantial positive inotropic action on neonatal lamb myocardium.