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Acta Pharmacol Sin ; 39(3): 382-392, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29072257

RESUMO

Short QT syndrome (SQTS) is a genetic arrhythmogenic disease that can cause malignant arrhythmia and sudden cardiac death. The current therapies for SQTS have application restrictions. We previously found that Mg· (NH2CH2CH2SO3)2· H2O, a taurine-magnesium coordination compound (TMCC) exerted anti-arrhythmic effects with low toxicity. In this study we established 3 different models to assess the potential anti-arrhythmic effects of TMCC on type 2 short QT syndrome (SQT2). In Langendorff guinea pig-perfused hearts, perfusion of pinacidil (20 µmol/L) significantly shortened the QT interval and QTpeak and increased rTp-Te (P<0.05 vs control). Subsequently, perfusion of TMCC (1-4 mmol/L) dose-dependently increased the QT interval and QTpeak (P<0.01 vs pinacidil). TMCC perfusion also reversed the rTp-Te value to the normal range. In guinea pig ventricular myocytes, perfusion of trapidil (1 mmol/L) significantly shortened the action potential duration at 50% (APD50) and 90% repolarization (APD90), which was significantly reversed by TMCC (0.01-1 mmol/L, P<0.05 vs trapidil). In HEK293 cells that stably expressed the outward delayed rectifier potassium channels (IKs), perfusion of TMCC (0.01-1 mmol/L) dose-dependently inhibited the IKs current with an IC50 value of 201.1 µmol/L. The present study provides evidence that TMCC can extend the repolarization period and inhibit the repolarizing current, IKs, thereby representing a therapeutic candidate for ventricular arrhythmia in SQT2.


Assuntos
Arritmias Cardíacas/prevenção & controle , Complexos de Coordenação/farmacologia , Sistema de Condução Cardíaco/anormalidades , Cardiopatias Congênitas/prevenção & controle , Magnésio/farmacologia , Taurina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/induzido quimicamente , Células Cultivadas , Cobaias , Cardiopatias Congênitas/induzido quimicamente , Humanos , Magnésio/química , Modelos Teóricos , Miócitos Cardíacos/fisiologia , Pinacidil/antagonistas & inibidores , Pinacidil/farmacologia , Taurina/química , Trapidil/antagonistas & inibidores , Trapidil/farmacologia
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