增加异氟醚麻醉时间，降低其最小肺泡有效浓度在7日龄小鼠而非60日龄小鼠的实验研究

背景在研究小鼠神经毒性的试验中，我们发现，7日龄小鼠的异氟醚最小肺泡有效浓度（minimumalveolaranestheticconcentration，MAC）随着麻醉时间的延长而降低，这种现象并没有发生在60日龄小鼠中。7日龄小鼠麻醉后15分钟，MAC为3．5％，而4小时为1．3％。为此我们研究是否药代学或药动学因素对MAC的降低有影响。方法在7日龄小鼠中，我们以MAC作为持续麻醉时间的参数，测量肺泡和脑异氟醚分压。在60曰龄小鼠中，我们以MAC作为持续麻醉时间的参数，测量肺泡异氟醚分压。最后，我们给予1mg＆g的纳洛酮和延迟尾部钳夹刺激对7日龄小鼠以确定MAC的影响。结果在7日龄小鼠麻醉后的1—4小时中，肺泡和脑的MAC值降低。肺泡MAC降低56％，而脑MAC降低33％，在4小时时，肺泡MAC值接近脑MAC值（分压无明显不同）。给予1mg／kg的纳洛酮并在3小时后开始尾部钳夹刺激，两者均不能逆转MAC的降低。60日龄小鼠肺泡异氟醚的MAC，在1—4小时麻醉过程中保持稳定。结论7日龄小鼠麻醉1—4小时后异氟醚MAC降低，但是这种现象并没有出现在60日龄小鼠。药效学和药动学因素共同导致了7日龄小鼠MAC的降低。内源性阿片肽与脱敏作用均不能调节药动学过程。

BACKGROUND： 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. METHODS： 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. RESULTS： 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 damping 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. CONCLUSIONS： 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.