Biomaterial Database

Kinetics of electrophysiologic changes during oral loading of amiodarone and after withdrawal of amiodarone in the unsedated dog. 1985

I C Tuna, and A C Qi, and C Gornick, and R M Bolman, and D G Benditt

We examined the temporal kinetics of onset and offset of the cardiac electrophysiologic effects of orally administered amiodarone in chronically instrumented, unsedated adult dogs (n = 8). Right atrial (RA), atrioventricular nodal (AVN), and right ventricular (RV) effective refractory period (ERP), and AVN functional refractory period (FRP), were determined daily for 21 days during amiodarone loading (24 mg/kg/day) and for 21 days after cessation of amiodarone. Left ventricular (LV) ERP was assessed in four of eight animals. Group mean RA-ERP peaked and plateaued early during amiodarone loading (time to reach one-half observed peak change [t1/2 onset] = 1.2 +/- 0.5 days) and rapidly returned toward baseline after cessation of drug (decay time to one-half peak value [t1/2 offset] = 2.0 +/- 1.7 days). Group mean RV-ERP rose in a linear manner throughout the loading period (t1/2 onset = 9.3 +/- 2.1 days) and remained elevated after cessation of drug (t1/2 offset greater than 21.0 days). Group mean AVN-ERP and FRP exhibited temporal kinetics intermediate between those of the RA-ERP and RV-ERP, both during amiodarone loading and after cessation of the drug. Group mean LV-ERP onset kinetics (assessed in a limited number of animals, n = 4) appeared to differ from RV-ERP onset kinetics (t1/2 onset = 2.5 +/- 2.5 days), whereas LV-ERP and RV-ERP offset kinetics appeared similar (t1/2 offset greater than 21 days). In summary, our findings demonstrate that during oral loading, the temporal sequence of onset of amiodarone-induced electrophysiologic effects is site dependent. Similarly, after cessation of amiodarone, the persistence of drug-induced electrophysiologic effects is both variable and site dependent.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D012032	Refractory Period, Electrophysiological	The period of time following the triggering of an ACTION POTENTIAL when the CELL MEMBRANE has changed to an unexcitable state and is gradually restored to the resting (excitable) state. During the absolute refractory period no other stimulus can trigger a response. This is followed by the relative refractory period during which the cell gradually becomes more excitable and the stronger impulse that is required to illicit a response gradually lessens to that required during the resting state.	Period, Neurologic Refractory,Periods, Neurologic Refractory,Refractory Period, Neurologic,Tetanic Fade,Vvedenskii Inhibition,Wedensky Inhibition,Inhibition, Vvedenskii,Inhibition, Wedensky,Neurologic Refractory Period,Neurologic Refractory Periods,Neuromuscular Fade,Neuromuscular Transmission Fade,Refractory Period, Neurological,Refractory Periods, Neurologic,Electrophysiological Refractory Period,Electrophysiological Refractory Periods,Fade, Neuromuscular,Fade, Neuromuscular Transmission,Fade, Tetanic,Neurological Refractory Period,Neurological Refractory Periods,Refractory Periods, Electrophysiological,Refractory Periods, Neurological,Transmission Fade, Neuromuscular
D002304	Cardiac Pacing, Artificial	Regulation of the rate of contraction of the heart muscles by an artificial pacemaker.	Pacing, Cardiac, Artificial,Artificial Cardiac Pacing,Artificial Cardiac Pacings,Cardiac Pacings, Artificial,Pacing, Artificial Cardiac,Pacings, Artificial Cardiac
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D006329	Heart Conduction System	An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart.	Conduction System, Heart,Conduction Systems, Heart,Heart Conduction Systems,System, Heart Conduction,Systems, Heart Conduction
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000638	Amiodarone	An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.	Amiobeta,Amiodarex,Amiodarona,Amiodarone Hydrochloride,Amiohexal,Aratac,Braxan,Corbionax,Cordarex,Cordarone,Kordaron,L-3428,Ortacrone,Rytmarone,SKF 33134-A,Tachydaron,Trangorex,Hydrochloride, Amiodarone,L 3428,L3428,SKF 33134 A,SKF 33134A
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001572	Benzofurans	Compounds that contain a BENZENE ring fused to a furan ring.	Coumarones,Diphenylbenzofuran