Stratmann Greg, Sall Jeffrey W, Eger Edmond I, Laster Michael J, Bell Joseph S, May Laura D V, Eilers Helge, Krause Martin, Heusen Frank v d, Gonzalez Heidi E
Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143, USA.
Anesth Analg. 2009 Sep;109(3):801-6. doi: 10.1213/ane.0b013e3181aff364.
While studying neurotoxicity in rats, we observed that the anesthetic minimum alveolar anesthetic concentration (MAC) of isoflurane decreases with increasing duration of anesthesia in 7-day-old but not in 60-day-old rats. After 15 min of anesthesia in 7-day-old rats, MAC was 3.5% compared with 1.3% at 4 h. We investigated whether kinetic or dynamic factors mediated this decrease.
In 7-day-old rats, we measured inspired and cerebral partial pressures of isoflurane at MAC as a function of duration of anesthesia. In 60-day-old rats, we measured inspired partial pressures of isoflurane at MAC as a function of duration of anesthesia. Finally, we determined the effect of administering 1 mg/kg naloxone and of delaying the initiation of the MAC determination (pinching the tail) on MAC in 7-day-old rats.
In 7-day-old rats, both inspired and cerebral measures of MAC decreased from 1 to 4 h. The inspired MAC decreased 56%, whereas the cerebral MAC decreased 33%. At 4 h, the inspired MAC approximated the cerebral MAC (i.e., the partial pressures did not differ appreciably). Neither administration of 1 mg/kg naloxone nor delaying tail clamping until 3 h reversed the decrease in MAC. In 60-day-old rats, inspired MAC of isoflurane was stable from 1 to 4 h of anesthesia.
MAC of isoflurane decreases over 1-4 h of anesthesia in 7-day-old but not in 60-day-old rats. Both pharmacodynamic and a pharmacokinetic components contribute to the decrease in MAC in 7-day-old rats. Neither endorphins nor sensory desensitization mediate the pharmacodynamic component.
在研究大鼠神经毒性时，我们观察到，异氟烷的麻醉最低肺泡浓度（MAC）在7日龄大鼠中随麻醉时间延长而降低，而在60日龄大鼠中则不然。7日龄大鼠麻醉15分钟后，MAC为3.5%，而4小时时为1.3%。我们研究了是动力学因素还是动态因素介导了这种降低。
在7日龄大鼠中，我们测量了MAC时异氟烷的吸入分压和脑分压随麻醉时间的变化。在60日龄大鼠中，我们测量了MAC时异氟烷的吸入分压随麻醉时间的变化。最后，我们确定了给7日龄大鼠注射1mg/kg纳洛酮以及延迟MAC测定起始时间（夹尾）对MAC的影响。
在7日龄大鼠中，MAC的吸入和脑测量值在1至4小时内均降低。吸入MAC降低了56%，而脑MAC降低了33%。在4小时时，吸入MAC接近脑MAC（即分压差异不明显）。注射1mg/kg纳洛酮或延迟夹尾至3小时均未逆转MAC的降低。在60日龄大鼠中，异氟烷的吸入MAC在麻醉1至4小时内保持稳定。
异氟烷的MAC在7日龄大鼠麻醉1至4小时内降低，而在60日龄大鼠中则不然。药效学和药代动力学成分均导致7日龄大鼠MAC降低。内啡肽和感觉脱敏均未介导药效学成分。
