Tetsutaro Hase1, Toshikazu Hashimoto2, Hitoshi Saito3, Yosuke Uchida3, Rui Kato4, Kenkichi Tsuruga3, Koichi Takita3, Yuji Morimoto3. 1. Department of Anesthesiology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. hasetarou0035@eis.hokudai.ac.jp. 2. Heiseikai Hospital, North 1 West 16, 1-1, Chuo-ku, Sapporo, Hokkaido, 060-0001, Japan. 3. Department of Anesthesiology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. 4. National Hospital Organization Tokyo Medical Center, Higashigaoka 2-5-1 Meguro-ku, Tokyo, 152-8902, Japan.
Abstract
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Entities:
Keywords:
Area postrema; Isoflurane; Ondansetron; c-Fos
Authors: Christian C Apfel; Kari Korttila; Mona Abdalla; Heinz Kerger; Alparslan Turan; Ina Vedder; Carmen Zernak; Klaus Danner; Ritva Jokela; Stuart J Pocock; Stefan Trenkler; Markus Kredel; Andreas Biedler; Daniel I Sessler; Norbert Roewer Journal: N Engl J Med Date: 2004-06-10 Impact factor: 91.245
Authors: C C Apfel; P Kranke; M H Katz; C Goepfert; T Papenfuss; S Rauch; R Heineck; C A Greim; N Roewer Journal: Br J Anaesth Date: 2002-05 Impact factor: 9.166