Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome

Abstract

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· (NHCHCHSO)2· HO, 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% (APD) and 90% repolarization (APD), 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 (I), perfusion of TMCC (0.01-1 mmol/L) dose-dependently inhibited the IKs current with an IC value of 201.1 μmol/L. The present study provides evidence that TMCC can extend the repolarization period and inhibit the repolarizing current, I, thereby representing a therapeutic candidate for ventricular arrhythmia in SQT2.

Energy drinks: a narrative review of their physiological and pathological effects

“…Taurine is a sulfur‐containing amino acid implicated in several biological and physiological functions in the human body, among which are important cardiovascular effects and influence on platelet aggregation, as well as neuromodulation of the central nervous system 52,53 . However, it may prolong the QT interval in a dose‐dependent manner, as animal studies suggest 54 …”

“…52,53 However, it may prolong the QT interval in a dose-dependent manner, as animal studies suggest. 54 In a randomised controlled trial comparing highvolume of Edks versus caffeinated control drinks, the participants consumed 946 mL (32 oz) of Edks or a caffeinated control beverage, both containing 320 mg of caffeine, separated by a 6-day washout period. 55 The change in the QT interval adjusted from baseline for the Edks group was significantly higher than in the 2-h caffeine group compared to the caffeinated control group (0.44 AE 18.4 ms vs −10.4 AE 14.8 ms respectively; P = 0.02).…”

The Acute Effects Of ATP-Sensitive Potassium Channel Opener (Pinacidil) And Blocker (Glimepride) On the Ischemia or Reperfusion-Induced Arrhythmias

“…Pinacidil was shown to decrease EAD with abnormal automaticity generated in the Purkinje cell (26). Pinacidil decreases the action potential and duration of QT interval (27,28) and increases the recovery of action potentials in ischemic cells (29). The heterogeneity in action potentials occurring in ischemic and non-ischemic cells is a major cause of arrhythmia.…”

Impacts of gene variants on drug effects-the foundation of genotype-guided pharmacologic therapy for long QT syndrome and short QT syndrome

“… 38 Additionally, the effective use of taurine-magnesium coordination compound (TMCC) in treating SQTS2 has been reported. 49 On SQTS3, several drugs have been tested, mainly in experimental settings. These include quinidine, 50 chloroquine, 5 , 51 , 52 gambogic acid (GA), 53 amiodarone, 54 disopyramide, E−4031 55 , 56 and a traditional Chinese medicine known as styrax.…”