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Direct Effects of Ketamine on Isolated Canine Cerebral and Mesenteric Arteries

Received from the Department of Anesthesiology, Yamaguchi University School of Medicine and Shimonoseki Kosei Hospital, and the Department of Pharmacology, Shiga University of Medical Sciences, Japan.

Abstract

The effects of ketamine on isolated canine cerebral (middle cerebral and basilar) and mesenteric arteries were studied. In arteries contracted with KCl, ketamine in concentrations above 5 x 10 ^–6M (cerebral arteries) or 2 x 10 ^–5M (mesenteric arteries) caused significant relaxation in a dose-dependent manner. The relaxation was not significantly influenced by aminophylline, aspirin, atropine, or propranolol. In concentrations above 5 x 10^–6M ketamine attenuated the contractile response to high concentrations of KCl in the middle cerebral arteries, and in concentrations above 5 x 10^–5M it attenuated the contractile response to high concentrations of KCl in the basilar and mesenteric arteries. The attenuation was greater in cerebral than in mesenteric arteries. The contractile response of cerebral arteries to high concentrations of serotonin was also attenuated by ketamine in concentrations above 5 x 10^–5M. Ketamine attenuated KCl-induced contraction of cerebral arteries more than it attenuated serotonin-induced contraction. When basilar arteries were exposed to Ca²⁺-free media and depolarized by KCl, the addition of Ca²⁺ caused biphasic (transient and sustained) contractions, while in the mesenteric arteries the addition of Ca²⁺ produced sustained contractions. Ketamine at 5 x 10^–5 and 5 x 10^–4M attenuated both transient and sustained contractions in basilar arteries, while in mesenteric arteries 5 x 10^–4M ketamine attenuated only sustained contractions. In both instances, ketamine-induced attenuation was partially reversed by excess Ca²⁺. It is concluded that ketamine has a direct dilating effect on both cerebral and mesenteric arteries, but the effect is more pronounced in cerebral than in mesenteric arteries. The direct action of ketamine on those arteries may be due in part to interference with transmembrane influx of Ca²⁺.

Key Words: ANESTHETICS, Intravenous: ketamine • ARTERIES: cerebral • IONS: calcium

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999