Proarrhythmic effects of the agents which delay repolarization in isoflurane anesthetized dogs

• Published in: Journal of Pharmacological Sciences Vol. 94; no. suppl.3; p. 265
• Main Authors: Kiyoshi Tadano, Takanobu Mochidome, Teruaki Iyama, Megumu Okada, Takahiro Fukuroda, Takeshi Tani, Masato Chiba, Yasuyuki Ishii, Masaru Nishikibe
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 2004
• ISSN: 1347-8613; 1347-8648

The drugs which delay repolarization produce QT prolongation and torsades de pointes (TdP). We examined how the prolongation of QT interval and incidence of TdP are affected by time period of drugs. MK499 and astemizole were used in this study. Each drug was administered intravenously over a period of 10 or 30-min to dogs under isoflurane anesthesia. In 30-min infusion, MK499 caused prolongation of QT interval by 30% at 10 μg/kg and was liable to he initiated TdP after a dosage of 30 μg/kg. In dogs given over 10-min. prolongation of QT interval was 25% at 10 μg/kg and TdP was hard to be developed at 30 kg/kg. When astemizole was administered at 0.3 mg/kg over 30-min, there was a prolongation of QT interval by 25%. TdP were induced in all 5 dogs at 1 mg/kg. In five dogs given at same dosages over 10-min, only one animal developed TdP, despite of similar prolongation of QT interval. The plasma concentration just after 10-min infusion of each drug was rather higher than that after 30-min infusion. The sensitivity to detect TdP of these drugs seems to be higher in longer period of infusion.