Biomaterial Database

Diverse electrophysiologic effects of propafenone and flecainide in canine Purkinje fibers: implications for antiarrhythmic drug classification. 1994

A Zaza, and G Malfatto, and P J Schwartz

Dipartimento di Fisiologia e Biochimica Generali, Universitá degli Studi di Milano, Italy.

Propafenone and flecainide are assigned to class Ic of the Campbell-Vaughan Williams classification because of their effects on ventricular muscle. The authors compared the use-dependent local anesthetic properties and the effects on repolarization of these drugs (1 and 5 microM) in Purkinje fibers. A reduction in maximum upstroke velocity was used as an index of the local anesthetic action. The rate dependency of the drug's effects on repolarization was evaluated by analyzing the relationship between action potential duration during steady-state stimulation and cycle length (CL). Tonic block was higher for propafenone (n = 10) than for flecainide (n = 7) at both concentrations tested (19 +/- 3% vs. 4 +/- 1% at 1 microM; 59 +/- 10% vs. 24 +/- 4% at 5 microM). Use-dependent block onset and dissipation were significantly slower for flecainide than for propafenone (e.g., at 1 microM and CL = 500 ms, time constant of block onset = 31 +/- 6 vs. 9 +/- 1 beats; time constant of recovery from block = 7.7 +/- 0.2 vs. 2.8 +/- 0.2 sec; P < .05). Steady-state block measured at each CL was compared with that predicted by a theoretical model of use dependency. Predictions approximated the experimentally results only for flecainide. At 1 microM, propafenone shortened action potential duration at all rates; flecainide had biphasic effects. At 5 microM, the effect of flecainide was similar to that of 1 microM propafenone. Thus, in Purkinje fibers, the kinetics of use-dependent local anesthetic effects and the effects on repolarization discriminate flecainide from propafenone.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011405	Propafenone	An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.	Apo-Propafenone,Arythmol,Baxarytmon,Cuxafenon,Fenoprain,Jutanorm,Nistaken,Norfenon,Pintoform,Prolecofen,Propafenon AL,Propafenon Hexal,Propafenon Minden,Propafenone Hydrochloride,Propafenone Hydrochloride, (R)-Isomer,Propafenone Hydrochloride, (S)-Isomer,Propafenone, (+-)-Isomer,Propafenone, (R)-Isomer,Propafenone, (S)-Isomer,Propamerck,Rythmol,Rytmo-Puren,Rytmogenat,Rytmonorm,SA-79,Hydrochloride, Propafenone,SA 79,SA79
D011690	Purkinje Fibers	Modified cardiac muscle fibers composing the terminal portion of the heart conduction system.	Purkinje Fiber,Fiber, Purkinje,Fibers, Purkinje
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
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005260	Female		Females
D005424	Flecainide	A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.	Flecainide Acetate,Apocard,Flecadura,Flecainid-Isis,Flecainide Monoacetate,Flecainide Monoacetate, (+-)-Isomer,Flecainide Monoacetate, (R)-Isomer,Flecainide Monoacetate, (S)-Isomer,Flecainide, (R)-Isomer,Flecainide, (S)-Isomer,Flecainide, 5-HO-N-(6-oxo)-Derivative,Flecainide, 5-HO-N-(6-oxo)-Derivative, (+-)-Isomer,Flecatab,Flécaïne,R818,Tambocor,Flecainid Isis
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential