Hemodynamic and myocardial effects of (-)-delta9-trans-tetrahydrocannabinol in anesthetized dogs |
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Authors: | I Cavero J P Buckley B S Jandhyala |
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Institution: | Department of Pharmacology, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pa. 15261, U.S.A. |
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Abstract: | (?)-Δ9-trans-tetrahydrocannabinol (Δ9-THC) (39 μg–2.5 mg/kg, i.v.) decreased blood pressure, heart rate, cardiac output and right ventricular contractile force in a dose-related manner in intact dogs under pentobarbital anesthesia. The Δ9-THC-induced hypotension appeared to result mainly from a consistent and reproducible attenuation of cardiac output since no marked alteration in total peripheral resistance occured. In these animals the decrease in cardiac output appeared to be related to the bradycardia since there was no change in stroke volume following Δ9-THC. However, when the change in heart rate was prevented by atrial pacing or cardiac denervation, a less but significant reduction in cardiac output was induced by Δ9-THC. Under these experimental conditions Δ9-THC also significantly attenuated stroke volume. In contrast, Δ9-THC did not induce any significant changes in cardiac output, blood pressure, and heart rate of dogs pretreated with a ganglionic blocker.Δ9-THC appeared to be devoid of any measurable direct effect on the myocardium since the compound neither significantly altered right ventricular contractile force of the denervated or ganglionic blocker-pretreated hearts nor interfered with the positive inotropic responses to i.v. calcium and isoproterenol.In the major vessel occlusion preparation administration of Δ9-THC was followed by a reduction in venous tone. Furthermore, measurements of blood and plasma volume excluded an effect of Δ9-THC in these parameters.From these findings it is suggested that the reduction in cardiac output induced by Δ9-THC is the result of the action of this compound on cardiac rate as well as venous return; no evidence could be documented for a direct effect of this compound on the myocardium. |
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Keywords: | Hypotension Cardiac output Myocardial contractile force Bradycardia Venous return |
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