Literature DB >> 33357775

In vivo comparison of dl-sotalol-induced electrocardiographic responses among halothane anesthesia, isoflurane anesthesia with nitrous oxide, and conscious state.

Hiroyuki Saito1, Ryuichi Kambayashi2, Mihoko Hagiwara-Nagasawa2, Yoshio Nunoi2, Ai Goto2, Hiroko Izumi-Nakaseko2, Shinichi Kawai3, Yoshinori Takei4, Akio Matsumoto5, Kiyotaka Hoshiai1, Yasuki Akie1, Atsushi Sugiyama6.   

Abstract

We compared dl-sotalol-induced electrocardiographic responses in intact dogs using a repeated-measures design among 1% halothane anesthesia, 1.5% isoflurane anesthesia with nitrous oxide (N2O), and conscious state to clarify influences of the anesthetics (n = 4). Basal PR interval was longer in halothane than either in isoflurane with N2O or in conscious state, reflecting sympathetic nerve suppression for the atrioventricular node by halothane. Both anesthetics exhibited longer basal QRS width than conscious state, suggesting their ventricular INa inhibition. Also, both anesthetics showed longer basal QT interval, QTcF and Tpeak-Tend than conscious state, indicating their ventricular IKr inhibition. Meanwhile, dl-sotalol prolonged PR interval similarly in isoflurane with N2O and in conscious state, which was less great in halothane, suggesting further sympathetic nerve suppression for the atrioventricular node might be limited in halothane. dl-Sotalol prolonged QT interval and QTcF >3 times greater in either of the anesthetics than in conscious state; moreover, dl-sotalol prolonged Tpeak-Tend similarly in both anesthetics, but hardly altered it in conscious state; indicating isoflurane with N2O as well as halothane may have reduced the repolarization reserve to increase the sensitivity of ventricle toward IKr suppression. Thus, isoflurane with nitrous oxide could be useful for in vivo IKr assay like halothane.
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Keywords:  Halothane; Isoflurane; Nitrous oxide; QT interval; dl-sotalol

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Year:  2020        PMID: 33357775     DOI: 10.1016/j.jphs.2020.10.001

Source DB:  PubMed          Journal:  J Pharmacol Sci        ISSN: 1347-8613            Impact factor:   3.337


  1 in total

Review 1.  Translational Models and Tools to Reduce Clinical Trials and Improve Regulatory Decision Making for QTc and Proarrhythmia Risk (ICH E14/S7B Updates).

Authors:  David G Strauss; Wendy W Wu; Zhihua Li; John Koerner; Christine Garnett
Journal:  Clin Pharmacol Ther       Date:  2021-01-07       Impact factor: 6.875

  1 in total

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