| Autor: |
Satoshi Kawakami, Ryuichi Kambayashi, Kazuhiro Takada, Megumi Aimoto, Yoshinobu Nagasawa, Akira Takahara |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Journal of Pharmacological Sciences, Vol 150, Iss 2, Pp 67-73 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1016/j.jphs.2022.07.003 |
| Popis: |
We analyzed role of cardiac α1-adrenoreceptors for the torsadogenic action of IKr blocker nifekalant in isoflurane-anesthetized atrioventricular block rabbits. Bradycardia was induced by atrioventricular node ablation, and the ventricle was electrically driven at a constant rate of 60 beats/min throughout the experiments to prevent rate-dependent modification by the IKr blocker in ventricular repolarization phase. Nifekalant (3 mg/kg per 10 min, n = 5) prolonged the duration of monophasic action potential (MAP90) by +178 ± 43 ms, increased the short-term variability of repolarization (STV) to 4.2 ± 1.2 ms, and induced torsade de pointes (TdP) in 1 animal. In the presence of methoxamine (n = 5), nifekalant prolonged the MAP90 by +328 ± 32 ms, increased the STV to 8.0 ± 1.0 ms, and induced TdP in 2 animals. In the presence of prazosin and methoxamine (n = 5), nifekalant prolonged the MAP90 by +267 ± 22 ms, increased the STV to 9.2 ± 3.6 ms, and induced no TdP. These results suggest that cardiac α1-adrenoreceptor activation by methoxamine essentially sensitizes the rabbit heart to nifekalant-induced QT interval prolongation, leading to the onset of TdP. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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