Effects of ambasilide in isolated perfused guinea pig heart: use dependence.
There has been increased interest in class III antiarrhythmic drugs for con-version of atrial fibrillation to sinus rhythm. Ambasilide, a class III antiarrhythmic, has been shown to block multiple cardiac channels in a variety of animals including humans. Although the electrophysiological effects of ambasilide are characterized on the cellular level, its effects on an organ level have yet to be investigated. We investigated escalating doses of ambasilide in isolated, per-fused guinea pig hearts. Ambasilide prolonged the RR, PQ, QRS, QT, and QTc (F) in a concentration-dependent manner in either normal sinus rhythm or with reduced heart rate (atriectomy). dP/dtmin was increased (became less negative) in the presence of increasing concentrations of ambasilide, whereas the vehicle produced less negative lusitropy. Ambasilide demonstrated use dependence by prolonging QTc (F) less at slower heart rates. Ambasilide also inhibited isoproterenol-induced tachycardia, suggesting it exerts beta-adrenergic blocking properties. In conclusion, this study suggests that ambasilide has multichannel blocking properties including beta-adrenergic antagonism.
Kijtawornrat
Anusak
A
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA. kijtawornrat.1@osu.edu
Hamlin
Robert L
RL
Hamlin
David M
DM
D062365:Aminobenzoates / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D010477:Perfusion
D062365:Aminobenzoates; D019086:Bridged Bicyclo Compounds, Heterocyclic; C075113:ambasilide