The effect of (minus)-delta 9-trans-tetrahydrocannibinol on myocardial contractility and venous return in anesthetized dogs |
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Authors: | I Cavero M F Lokhandwala J P Buckley B S Jandhyala |
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Institution: | 1. Department of Pharmacology, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennyslvania 15261, USA;2. Division of Cardiovascular Research, College of Pharmacy, University of Houston, Houston, Texas 77004, U.S.A. |
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Abstract: | Administration of (?)-Δ9-trans-tetrahydrocannabinol (Δ9-THC, 2.5 mg/kg i.v.) to pentobarbital-anesthetized dogs in which heart rate was maintained constant by electrical pacing, decreased aortic blood pressure, cardiac output, left ventricular peak pressure and left ventricular end diastolic pressure and dP/dt. However, the contractility index (max. dP/dt)/I.P. was not altered by the compound. Furthermore, it was shown that the decrease in cardiac output due to Δ9-THC could be restored to original levels by an infusion of saline-dextran in quantities sufficient to elevate the left ventricular end diastolic pressure to pre-Δ9-THC level.In dogs in which cardiac output was maintained constant by a right heart bypass procedure Δ9-THC decreased blood pressure and total peripheral resistance and augmented intravascular blood volume. This increase in intravascular blood volume was significantly less (74%) in animals in which the splanchnic (superior, inferior and celiac) arteries were ligated prior to the administration of Δ9-THC. On the other hand, in spinal dogs Δ9-THC was devoid of any measurable cardiovascular effects.These observations clearly support the hypothesis that the diminution of cardiac output induced by Δ9-THC in animals with constant cardiac rate is primarily due to diminished venous return to the heart and not to an impaired ability of the myocardium. |
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Keywords: | Cardiac output Conctractility index Left ventricular performance Venous return Right heart bypass |
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