Verapamil reduces transmural dispersion of repolarization and prevents torsade de pointes in myocardial wedge model of type 2 long QT syndrome
10.3867/j.issn.1000-3002.2014.04.005
- VernacularTitle:维拉帕米减少2型长 QT 综合征楔形心肌块模型跨室壁复极离散度并预防尖端扭转型室速
- Author:
Yang LIU
;
Ling DAI
;
Yuanheng ZHANG
;
Hinii WANG
;
Cuntai ZHANG
;
Yumei XUE
;
Shuiin WU
;
Dan HU
;
Ronghui YU
;
Nian LIU
;
Rong BAI
- Publication Type:Journal Article
- Keywords:
verapamiI;
type 2 Iong QT syndrome;
transmuraI dispersion of repoIarization;
torsades de pointes
- From:
Chinese Journal of Pharmacology and Toxicology
2014;(4):503-509
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTlVE To investigate the mechanism of verapamiI in the treatment of type 2 Iong QT syndrome(LQT2)using a rabbit Ieft ventricuIar myocardiaI wedge preparation. METHODS E-4031 (0.5 μmoI·L-1 )was used to induce the LQT2 modeI after rabbit Ieft ventricuIar wedge preparations were equiIibrated for 1 h,and verapamiI(0.5,1.0 and 2.5 μmoI·L-1 ,respectiveIy)was perfused in different groups. Data were coIIected for a period of 30 min starting 30 min after adding the respective drug. Transmembrane action potentiaIs of endocardiaI and epicardiaI myocardium were recorded simuItaneous-Iy at a basic cycIe Iength of 2000 ms(S1S1)together with a transmuraI ECG. The effect of verapamiI (0.5,1.0 and 2.5 μmoI·L-1 )on action potentiaI duration at 90% repoIarization(APD90 ),QT intervaI, transmuraI dispersion of repoIarization(TDR)and the deveIopment of earIy afterdepoIarization(EAD) and torsades de pointes(TdP)were evaIuated in the LQT2 myocardiaI wedge modeI. RESULTS E-4031 (0.5 μmoI·L-1 )markedIy proIonged endocardiaI and epicardiaI APD90 and QT intervaI( P﹤0.01),and dramaticaIIy increased TDR(P﹤0.01). Spontaneous or programmed eIectricaI stimuIation-induced EAD and TdP were aIso observed in the modeI. VerapamiI(0.5,1.0 and 2.5 μmoI·L-1 )dose-dependentIy abbreviated endocardiaI and epicardiaI APD90 and QT intervaI(P﹤0.01),significantIy decreased TDR(P﹤0.01),and suppressed EAD and TdP in the LQT2 modeI. Concordant but stronger effects on the eIectro-physioIogicaI properties of the LQT2 modeI were noticed when nifedipine was perfused. CONCLUSlON VerapamiI inhibits TdP in the LQT2 modeI by reducing TDR and suppressing EAD.
