Thermogenesis Inhibition in Brown Adipocytes Is a Specific Property of Volatile Anesthetics

Abstract

Background This investigation examined the possibility that the inhibitory effect of halothane on nonshivering thermogenesis (heat production) in brown adipocytes is not a universal effect of all anesthetic agents but related to the type of anesthetic. Methods Brown adipocytes from hamster were isolated with a collagenase digestion method and incubated with anesthetic agents. The rate of oxygen consumption was measured with an oxygen electrode. The effect of clinically relevant (and higher) doses of anesthetics of different classes on basal and norepinephrine-induced thermogenesis (oxygen consumption) was tested. Results Two distinct groups of anesthetics could be distinguished: thermogenesis inhibitors and noninhibitors. Thermogenesis inhibitors include volatile anesthetics such as halothane (IC(50), 1.1 mm), ether (IC(50), 20 mm), and chloroform (IC(50), 2.2 mm) (nominal concentrations), but also tribromoethanol (IC(50), 0.6 mm), all inducing inhibition of norepinephrine-induced thermogenesis without affecting the EC for norepinephrine. Thermogenesis noninhibitors include the nonvolatile anesthetics pentobarbital, propofol, ketamine, and urethane, the inhalation anesthetic nitrous oxide, and, notably, also the volatile nonanesthetics (nonimmobilizers) 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane; none of these compounds had any effect on norepinephrine-induced thermogenesis at any concentration tested. Conclusions There are two distinct classes of anesthetics with regard to effects on thermogenesis, thermogenesis inhibitors and thermogenesis noninhibitors. The results are important for the interpretation of studies in thermal biology in general; specifically, they indicate that conclusions concerning regulation of nonshivering thermogenesis during anesthesia depend on the type of anesthetic used. Of clinical importance is that the volatile anesthetics are inhibitory for nonshivering thermogenesis and thus for an alternative heat production when myorelaxants prevent shivering. As the distinction between thermogenesis inhibitors and thermogenesis noninhibitors corresponds to the distinction between volatile and nonvolatile anesthetics, it may be related to the mode of action of the volatile anesthetics.