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Titolo:
DIVERSE ELECTROPHYSIOLOGIC EFFECTS OF PROPAFENONE AND FLECAINIDE IN CANINE PURKINJE-FIBERS - IMPLICATIONS FOR ANTIARRHYTHMIC DRUG CLASSIFICATION
Autore:
ZAZA A; MALFATTO G; SCHWARTZ PJ;
Indirizzi:
UNIV MILAN,IST CLIN MED GEN & TERAPIA MED,VIA FRANCESCO SFORZA 35 I-20122 MILAN ITALY IRCCS,CTR AUXOLOG ITALIANO,DIPARTIMENTO FISIOL & BIOCHIM GEN MILAN ITALY UNIV PAVIA,DIPARTIMENTO MED INTERNA I-27100 PAVIA ITALY
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 269, anno: 1994,
pagine: 336 - 343
SICI:
0022-3565(1994)269:1<336:DEEOPA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTION-POTENTIAL DURATION; LIGAND-BINDING; CYCLE LENGTH; VENTRICULAR MYOCYTES; DEPENDENCE; MECHANISMS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
A. Zaza et al., "DIVERSE ELECTROPHYSIOLOGIC EFFECTS OF PROPAFENONE AND FLECAINIDE IN CANINE PURKINJE-FIBERS - IMPLICATIONS FOR ANTIARRHYTHMIC DRUG CLASSIFICATION", The Journal of pharmacology and experimental therapeutics, 269(1), 1994, pp. 336-343

Abstract

Propafenone and flecainide are assigned to class Ic of the Campbell-Vaughan Williams classification because of their effects on ventricularmuscle. The authors compared the use-dependent local anesthetic properties and the effects on repolarization of these drugs (1 and 5 mu M) in Purkinje fibers. A reduction in maximum upstroke velocity was used as an index of the local anesthetic action. The rate dependency of thedrug'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 mu M; 59 +/- 10% vs. 24 +/- 4% at 5 mu M). Use-dependent block onset and dissipation were significantly slower for flecainide than for propafenone (e.g., at 1 mu M and CL = 500 ms, time constant of block onset = 31 +/- 6 vs. 9 c 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 mu M propafenone shortened action potential duration at all rates; flecainide had biphasic effects. At 5 mu M, the effect of flecainide was similar to that of 1 mu M propafenone. Thus, in Purkinje fibers, the kinetics of use-dependent local anesthetic effects and the effects on repolarization discriminate flecainide from propafenone.

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Documento generato il 01/04/20 alle ore 23:27:38