Department of Anesthesiology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Heiseikai Hospital, North 1 West 16, 1-1, Chuo-ku, Sapporo, Hokkaido, 060-0001, Japan.
J Anesth. 2019 Aug;33(4):562-566. doi: 10.1007/s00540-019-02662-0. Epub 2019 Jul 17.
Volatile anesthetics are speculated to cause postoperative nausea and vomiting via stimulation of the chemoreceptor trigger zone (CTZ). However, the precise mechanism underlying the emetic action of these drugs is not well understood. In this study, we assessed whether isoflurane induced the expression of c-Fos, a neuronal activation marker, in the area postrema (AP), the locus of the CTZ, in rats, which do not have vomiting action.
Male rats were exposed to 1.3% isoflurane for 0-240 min, or to various concentrations of isoflurane (0, 1.3%, or 2.6%) for 120 min. Finally, the rats were exposed to 1.3% isoflurane for 120 min after ondansetron administration. After the treatments, immunohistochemistry of the rat AP was performed using c-Fos antibody staining.
One-way analysis of variance showed that isoflurane exposure significantly increased c-Fos expression in the AP; however, the rats pretreated with 4 mg/kg ondansetron showed significantly decreased c-Fos expression. Moreover, we evaluated the effect of the anesthetic on inducing pica in the rats, and found that kaolin intake was not influenced by isoflurane exposure.
Overall, these results suggest that isoflurane activates AP neurons and may be involved in the emetic mechanism of isoflurane. This study further suggests the feasibility of using rats as a model for studying emetic mechanisms of drugs, despite their lack of vomit action.
挥发性麻醉剂通过刺激化学感受器触发区(CTZ)被推测会引起术后恶心和呕吐。然而,这些药物致吐作用的确切机制尚不清楚。在这项研究中,我们评估了异氟醚是否会引起大鼠的后极(AP)即 CTZ 区域中神经元激活标志物 c-Fos 的表达,因为大鼠没有呕吐作用。
雄性大鼠暴露于 1.3%异氟醚 0-240 分钟,或暴露于不同浓度的异氟醚(0、1.3%或 2.6%)120 分钟。最后,在给予昂丹司琼后,大鼠暴露于 1.3%异氟醚 120 分钟。治疗后,通过 c-Fos 抗体染色对大鼠 AP 进行免疫组织化学染色。
单因素方差分析显示,异氟醚暴露显著增加了 AP 中的 c-Fos 表达;然而,预先给予 4mg/kg 昂丹司琼的大鼠显示 c-Fos 表达显著降低。此外,我们评估了麻醉剂对诱导大鼠嗜食癖的影响,发现异氟醚暴露并不影响高岭土的摄取。
总的来说,这些结果表明异氟醚激活了 AP 神经元,可能参与了异氟醚的致吐机制。这项研究进一步表明,尽管大鼠没有呕吐作用,但可以使用大鼠作为研究药物致吐机制的模型。