Basal vagal nerve activity does not predict susceptibility to dofetilide-induced torsade de pointes in anaesthetized rabbits

Autor: András Farkas, András Varró, Julius Gy. Papp, Miklós Csanády, László Rudas, Attila S. Farkas, Tamás Forster, Szabolcs Orosz, Norbert Csík, István Leprán
Rok vydání: 2006
Předmět:
Zdroj: Journal of Molecular and Cellular Cardiology. 40:984
ISSN: 0022-2828
Popis: 1643 activated human HERG channels in a heterologous expression system, whereas Na and Ca-channels were not blocked by the agent. Here we describe the effects of NS1643 on force of contraction and action potential parameters in isolated guinea pig papillary muscles. NS 1643 (10 AM) affected mainly the late phase of depolarisation: APD90 was decreased from 156 T 6 to 137 T 13 ms (mean T SEM, n = 5, P < 0.05) whereas APD20 remained unaffected compared to time-matched controls. Frequencydependency of the effect on APD90 was not observed. Resting membrane potential (-87 T 0.4 mV) and upstroke velocity (229 T 21 V/s) were not affected up to concentrations of 30 AM and 100 AM respectively. The shortening of APD with 10 AM NS1643 was accompanied by a small negative inotropic effect. Force of contraction decreased from 59 T 8 to 33 T 5 AN (n = 5) in the presence of 10 AMNS1643, for comparison in TMC from 89 T 14 to 69 T 14 AN. Activation of IKr by NS1643 effectively shortens AP in guinea pig papillary muscle. Excitability and conduction seem to be unaffected. The small negative inotropic effect could be related to the shortening of action potentials.
Databáze: OpenAIRE