Analysis of the Positive Inotropic Effect of Ibopamine in the Blood-Perfused Canine Papillary Muscle

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Abstract
The positive inotropic effect of ibopamine, an orally active dopamine analogue, was examined in an isolated canine papillary muscle perfused with blood of a donor dog through the anterior septal artery (ASA). Administered intraduodenally (25 mg/kg) in the donor dog, ibopamine increased the left ventricular dP/dtmax as well as the contractile force of the isolated papillary muscle. Injected into the ASA (10 μg) it had only a slight positive inotropic effect, which was greatly enhanced by preincubation of the drug in plasma. Addition of physostigmine to the plasma prevented this enhancement. Propranolol (0.2 mg/kg i.v.) shifted the dose-response curves for the positive inotropic effect of plasma-dissolved (PD) ibopamine (0.3–10 μg), norepinephrine (NE; 1–100 ng), and deoxyepinephrine (Epinine; 0.3–10 μg) to the right. At 3 μg/min cocaine enhanced the response to NE, but enhanced only slightly the responses to Epinine and PD ibopamine; at 10 μg/ml it enhanced the response to NE, but depressed slightly the responses to Epinine and PD ibopamine. The positive inotropic effect of intraduodenally administered ibopamine may be caused by active metabolite(s), possibly epinine, from its hydrolysis by ester-ases, and may be mediated by both direct and indirect stimulation of β-adrenoceptors in the canine heart.

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