Halothane Sensitizes the Guinea-Pig Heart to Pharmacological IKr Blockade: Comparison With Urethane Anesthesia
Potential utility of halothane-anesthetized guinea pigs for detecting drug-induced repolarization delay was analyzed in comparison with urethane-anesthesia (n = 4 for both groups). Basal QT interval was significantly greater under halothane-anesthesia than urethane-anesthesia (192 ± 7 vs 132 ± 5 ms,...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319321152 |
| _version_ | 1811287229589356544 |
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| author | Yasue Sakaguchi Atsushi Sugiyama Shuji Takao Yasuki Akie Akira Takahara Keitaro Hashimoto |
| author_facet | Yasue Sakaguchi Atsushi Sugiyama Shuji Takao Yasuki Akie Akira Takahara Keitaro Hashimoto |
| author_sort | Yasue Sakaguchi |
| collection | DOAJ |
| description | Potential utility of halothane-anesthetized guinea pigs for detecting drug-induced repolarization delay was analyzed in comparison with urethane-anesthesia (n = 4 for both groups). Basal QT interval was significantly greater under halothane-anesthesia than urethane-anesthesia (192 ± 7 vs 132 ± 5 ms, respectively), whereas the reverse was true for the heart rate (190 ± 7 vs 248 ± 11 beats/min, respectively). The typical IKr-blocker dl-sotalol (0.1 to 3mg/kg, i.v.) induced dose-related bradycardia and QT interval prolongation under each anesthesia. The extent of maximum prolongation in the QT interval was greater under halothane-anesthesia than urethane-anesthesia (+101 ± 15 vs +49 ± 3 ms, respectively), whereas that of peak change in the heart rate was smaller under the former than the latter (−49 ± 8 vs −63 ± 5 beats/min, respectively). Pretreatment of the animals under urethane-anesthesia with the selective IKs blocker chromanol 293B (n = 6) increased the extent of the dl-sotalol-induced QT interval prolongation to +57 ± 8 ms, which was only 0.56 times of that under the halothane-anesthesia, whereas the pretreatment increased the peak change in the heart rate to −76 ± 12 ms. These results indicate that the halothane-anesthesia may effectively sensitize the guinea-pig heart to pharmacological IKr blockade. Keywords:: QT interval prolongation, sotalol, halothane, urethane |
| first_indexed | 2024-04-13T03:15:04Z |
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| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-13T03:15:04Z |
| publishDate | 2005-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-2dcf8eda598f49a2bf83bdff938a70022022-12-22T03:04:57ZengElsevierJournal of Pharmacological Sciences1347-86132005-01-01992185190Halothane Sensitizes the Guinea-Pig Heart to Pharmacological IKr Blockade: Comparison With Urethane AnesthesiaYasue Sakaguchi0Atsushi Sugiyama1Shuji Takao2Yasuki Akie3Akira Takahara4Keitaro Hashimoto5Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan; Fuji Biomedix Co., Ltd., Kobuchisawa-cho, Kitakoma-gun, Yamanashi 408-0044, JapanDepartment of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan; Corresponding author. FAX: +81-55-273-6739 E-mail: atsushis@yamanashi.ac.jpFuji Biomedix Co., Ltd., Kobuchisawa-cho, Kitakoma-gun, Yamanashi 408-0044, JapanFuji Biomedix Co., Ltd., Kobuchisawa-cho, Kitakoma-gun, Yamanashi 408-0044, JapanDepartment of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, JapanDepartment of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, JapanPotential utility of halothane-anesthetized guinea pigs for detecting drug-induced repolarization delay was analyzed in comparison with urethane-anesthesia (n = 4 for both groups). Basal QT interval was significantly greater under halothane-anesthesia than urethane-anesthesia (192 ± 7 vs 132 ± 5 ms, respectively), whereas the reverse was true for the heart rate (190 ± 7 vs 248 ± 11 beats/min, respectively). The typical IKr-blocker dl-sotalol (0.1 to 3mg/kg, i.v.) induced dose-related bradycardia and QT interval prolongation under each anesthesia. The extent of maximum prolongation in the QT interval was greater under halothane-anesthesia than urethane-anesthesia (+101 ± 15 vs +49 ± 3 ms, respectively), whereas that of peak change in the heart rate was smaller under the former than the latter (−49 ± 8 vs −63 ± 5 beats/min, respectively). Pretreatment of the animals under urethane-anesthesia with the selective IKs blocker chromanol 293B (n = 6) increased the extent of the dl-sotalol-induced QT interval prolongation to +57 ± 8 ms, which was only 0.56 times of that under the halothane-anesthesia, whereas the pretreatment increased the peak change in the heart rate to −76 ± 12 ms. These results indicate that the halothane-anesthesia may effectively sensitize the guinea-pig heart to pharmacological IKr blockade. Keywords:: QT interval prolongation, sotalol, halothane, urethanehttp://www.sciencedirect.com/science/article/pii/S1347861319321152 |
| spellingShingle | Yasue Sakaguchi Atsushi Sugiyama Shuji Takao Yasuki Akie Akira Takahara Keitaro Hashimoto Halothane Sensitizes the Guinea-Pig Heart to Pharmacological IKr Blockade: Comparison With Urethane Anesthesia Journal of Pharmacological Sciences |
| title | Halothane Sensitizes the Guinea-Pig Heart to Pharmacological IKr Blockade: Comparison With Urethane Anesthesia |
| title_full | Halothane Sensitizes the Guinea-Pig Heart to Pharmacological IKr Blockade: Comparison With Urethane Anesthesia |
| title_fullStr | Halothane Sensitizes the Guinea-Pig Heart to Pharmacological IKr Blockade: Comparison With Urethane Anesthesia |
| title_full_unstemmed | Halothane Sensitizes the Guinea-Pig Heart to Pharmacological IKr Blockade: Comparison With Urethane Anesthesia |
| title_short | Halothane Sensitizes the Guinea-Pig Heart to Pharmacological IKr Blockade: Comparison With Urethane Anesthesia |
| title_sort | halothane sensitizes the guinea pig heart to pharmacological ikr blockade comparison with urethane anesthesia |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319321152 |
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