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ANESTHETIC PHARMACOLOGY

The Effects of Enflurane, Isoflurane, and Intravenous Anesthetics on Rat Diaphragmatic Function and Fatigability

Department of Anaesthesia & Perioperative Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

Address correspondence and reprint requests to Dr. Katsuya Mikawa, Department of Anaesthesia & Perioperative Medicine, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kusunoki-cho 7, Chuo-ku, Kobe 650-0017, Japan. Address e-mail to katz{at}post.med.kobe-u.ac.jp

We examined the effect of isoflurane, enflurane, midazolam, ketamine, propofol, and thiopental on diaphragmatic functions under unfatigued and fatigued conditions in 228 rat isolated muscle strips. Diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to one of the anesthetics at clinically relevant plasma concentrations, and at 10 and 100 times this concentration, or at 1, 2, and 3 minimum alveolar anesthetic concentration (MAC). Isoflurane, midazolam, ketamine, propofol, and thiopental did not induce a direct inotropic or lusitropic effect under unfatigued and fatigued conditions. Enflurane did not change contraction or relaxation in fresh isolated diaphragm, but enflurane at 2–3 MAC enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. These effects were greater at 3 MAC than at 2 MAC. Our findings suggest that the reduction of diaphragm function previously reported in in vivo experiments using propofol, midazolam, and isoflurane is not related to a direct effect on intrinsic diaphragmatic contractility. Our results also indicate that large concentrations of enflurane may impair the diaphragmatic function at sites other than excitation-contraction coupling.

IMPLICATIONS: Enflurane did not change contraction or relaxation in fresh isolated rat diaphragm, but enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. Isoflurane, midazolam, ketamine, propofol, and thiopental had no direct effects on diaphragmatic functions under unfatigued and fatigued conditions. Isoflurane and these IV anesthetics may be advantageous over enflurane to anesthetize and/or sedate patients who are predisposed to diaphragmatic fatigue.

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