title: Midazolam in rabbits terminates dysrhythmias caused by intracerebroventricular ropivacaine.
abstract: The current study was designed to investigate the mechanisms by which ropivacaine may act within the central nervous system (CNS) to produce cardiotoxicity. Eighty New Zealand rabbits were divided into four groups randomly. In Group 1, 20 rabbits received intracerebroventricular (icv) saline, and then received icv ropivacaine 30 min later. In Group 2, 20 rabbits received icv ropivacaine. Whenever dysrhythmias continued for more than 5 min, 0.1 ml saline was administered into the left cerebral ventricle. Ten minutes later, 0.1 ml midazolam was given into the left lateral ventricle. In Group 3, 20 rabbits received icv ropivacaine, and once the dysrhythmias developed, the inspired isoflurane concentration was increased from 0.75% to 1.50%. In Group 4, 20 animals received an intravenous (iv) phenylephrine infusion until dysrhythmias occurred. In Group 1, the rabbits did not develop dysrhythmias in response to icv saline, whereas dysrhythmias did develop in these animals after icv ropivacaine. In Group 2, icv saline had no effect on the dysrhythmias; however, icv midazolam terminated cardiac dysrhythmias. In Group 3, an increase in the concentration of the inspired isoflurane had no effect on dysrhythmias. In Group 4, icv midazolam had no effect on dysrhythmias in response to iv phenylephrine. Ropivacaine administered directly into the CNS is capable of producing cardiac dysrhythmias; midazolam terminated dysrhythmias presumably by potentiation of γ-aminobutyric acid (GABA) receptor activity. Our results suggest that ropivacaine produces some of its cardiotoxicity not only by the direct cardiotoxicity of the drug, but also by the CNS effects of ropivacaine.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. yaomin_zhu@126.com
authors.forename: Yao-Min
authors.initials: YM
authors.lastname: Zhu
authors.forename: Zu-Yi
authors.initials: ZY
authors.lastname: Yuan
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhou
authors.forename: Gui-Xia
authors.initials: GX
authors.lastname: Jing
mesh_terms: D000577:Amides / Q000009:adverse effects*; D000779:Anesthetics, Local / Q000009:adverse effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D001794:Blood Pressure; D002490:Central Nervous System / Q000187:drug effects; D018757:GABA Modulators / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D011817:Rabbits; D000077212:Ropivacaine; D013997:Time Factors
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D018757:GABA Modulators; D000077212:Ropivacaine; D008874:Midazolam