Thermogenesis in brown adipocytes is inhibited by volatile anesthetic agents. A factor contributing to hypothermia in infants?

Abstract

Background: In infants, nonshivering thermogenesis from brown adipose tissue provides an important source of heat for thermoregulation. Infants are known to have a high susceptibility to hypothermia during anesthesia. To investigate whether this could be due to an inhibition of nonshivering thermogenesis by anesthetics, the effect of preincubation with volatile anesthetics on the norepinephrine-induced heat production of brown adipocytes was investigated.

Methods: Brown adipocytes from hamsters were isolated with a collagenase digestion method and preincubated with volatile anesthetics. The cells were stimulated with norepinephrine, and heat production, measured as oxygen consumption, was monitored polarographically.

Results: Norepinephrine addition led to a 20-fold increase in the rate of oxygen consumption (thermogenesis). However, preincubation of cells with 3% halothane reduced the response to norepinephrine by more than 70%. The potency of norepinephrine (the median effective concentration) was not affected by halothane. Full effect of halothane was reached quickly, and after halothane withdrawal, the thermogenic response recovered, although rather slowly. Halothane, isoflurane, and enflurane were approximately equipotent inhibitors of thermogenesis, with concentrations of approximately 0.7% resulting in 50% inhibition. The inhibitory effect of 1% halothane was unaffected by the presence of 74% nitrous oxide, but nitrous oxide alone also reduced thermogenesis.

Conclusions: Volatile anesthetics severely attenuated the thermogenic response to norepinephrine of isolated brown-fat cells. It is inferred that brown-adipose-tissue heat production is reduced during (and probably also some time after) anesthesia. Because infants are dependent on brown-fat-derived nonshivering thermogenesis for thermal balance, the inhibition by volatile anesthetic agents of brown-adipocyte heat production may at least partly explain the susceptibility of infants to hypothermia during and after anesthesia.