title: Slowing Na+ channel inactivation prolongs QT interval and aggravates adrenaline-induced arrhythmias.
abstract: We investigated the effects of prolonged repolarization induced by slowed inactivation of Na+ channel on adrenaline-induced arrhythmias in halothane anesthetized, closed-chest dogs. We used sea anemone toxins (ATX-II and Anthopleurin-A) to prolong ventricular repolarization and examined their effects on adrenaline arrhythmias. Sea anemone toxins prolonged the QTc- and JTc-intervals (P<0.01), but did not affect the PQ interval, QRS duration, heart rate and mean blood pressure. Although sea anemone toxins did not induce any arrhythmias by themselves, under the treatment with these toxins, arrhythmias were induced by non-arrhythmia-inducing doses of adrenaline in four dogs out of seven and the control arrhythmias induced by adrenaline were aggravated. These results indicate that, similar to the inhibition of K+ channels by class III drugs, which we have already reported, slowing Na+ channel inactivation with QTc prolongation also aggravates adrenaline-induced arrhythmias.
authors: Department of Pharmacology, Yamanashi Medical University, Nakakoma-gun, Japan. miyamoto@res.yamanashi-med.ac.jp
authors: S
authors: S
authors: Miyamoto
authors: B M
authors: BM
authors: Zhu
authors: N N
authors: NN
authors: Aye
authors: K
authors: K
authors: Hashimoto
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D003064:Cnidarian Venoms / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D026941:Sodium Channel Blockers; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D003064:Cnidarian Venoms; D026941:Sodium Channel Blockers; D014662:Vasoconstrictor Agents; D004837:Epinephrine