Ohlson K B, Mohell N, Cannon B, Lindahl S G, Nedergaard J
Wenner-Gren Institute, Arrhenius Laboratories, Stockholm University, Sweden.
Anesthesiology. 1994 Jul;81(1):176-83. doi: 10.1097/00000542-199407000-00024.
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.
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.
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.
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.
在婴儿中，棕色脂肪组织的非寒战产热为体温调节提供了重要的热量来源。已知婴儿在麻醉期间对体温过低高度敏感。为了研究这是否可能是由于麻醉剂抑制了非寒战产热，研究了挥发性麻醉剂预孵育对去甲肾上腺素诱导的棕色脂肪细胞产热的影响。
采用胶原酶消化法分离仓鼠的棕色脂肪细胞，并与挥发性麻醉剂进行预孵育。用去甲肾上腺素刺激细胞，并通过极谱法监测以耗氧量衡量的产热情况。
添加去甲肾上腺素导致耗氧率（产热）增加20倍。然而，用3%氟烷预孵育细胞可使对去甲肾上腺素的反应降低70%以上。去甲肾上腺素的效价（半数有效浓度）不受氟烷影响。氟烷的全部作用迅速达到，撤去氟烷后，产热反应虽恢复缓慢，但仍能恢复。氟烷、异氟烷和恩氟烷对产热的抑制作用大致相当，浓度约为0.7%时可导致50%的抑制。1%氟烷的抑制作用不受74%氧化亚氮存在的影响，但单独使用氧化亚氮也会降低产热。
挥发性麻醉剂严重减弱了分离的棕色脂肪细胞对去甲肾上腺素的产热反应。据推测，在麻醉期间（可能还有麻醉后的一段时间内）棕色脂肪组织的产热会减少。由于婴儿依赖棕色脂肪来源的非寒战产热来维持热平衡，挥发性麻醉剂对棕色脂肪细胞产热的抑制作用可能至少部分解释了婴儿在麻醉期间及麻醉后对体温过低的易感性。
