Effect of Thimerosal on Arrhythmia Induced by Coronary Ligation The Involvement of ATP-dependent Potassium Channels

Abstract

SUMMARYThiol-modifying agents induce the release of nitric oxide (NO) from endothelial epithelium and the release of reactive oxygen free radicals in the vascular system. Moreover, thiol groups are essential for the functioning of the ATP dependent potassium channel (K-ATP). The effects of thiol-modifying agents and their molecular mechanisms on arrhythmia have not been widely studied. In this study, we investigated the effect of the hydrophilic SH-group-oxidizing substance thimerosal on the arrhythmia induced by reperfusion/ischemia after coronary artery ligation in rats. We studied the possible involvement of the K-ATP and NOS on the effect of thimerosal. Thimerosal pretreatment (3, 30 mg/kg dose iv. 10 minutes before coronary occlusion) significantly decreased the length of total arrhythmia, ventricular tachycardia, and the arrhythmia score. This effect of thimerosal was reversed by the K-ATP opener pinacidil but not by the K-ATP blocker glibenclamide. The inhibition of iNOS by L-NAME did not alter the antiarrhythmic effect of thimerosal. These data clearly suggest that the antiarrhythmic effect of thimerosal is dependent upon the blockage of K-ATP. ( 1) The activity of some K + channels is drastically altered by the oxidation of critical SH-groups of the channel protein. An interesting example is the loss of rapid inactivation of the voltage-gated K + channel RCK4 (Kv1.4) produced by oxidation of a thiol group; this residue is located near the intracellular inactivation (ball) domain of the channel.2) ATP-sensitive K + channels (K-ATP channels) in skeletal muscle, 3,4) heart 5) and pancreatic β-cells or insulin-secreting cellFrom the

Comparison of thiopental and ketamine+xylazine anesthesia inischemia/reperfusion-induced arrhythmias in rats

“…It has been shown that ATP dependent potassium (K ATP ) channel blockage confers protection against I/Rinduced arrhythmias (23,24). Ketamine inhibits the K ATP channel activity in a concentration-dependent manner in the rat heart (41).…”

“…Both thiopental and ketamine+xylazine (K+X) have been used in studies involving experimental cardiology (16)(17)(18)(19)(20)(21)(22)(23)(24). However, there are only a few studies addressing the influence of anesthetics on I/R-induced arrhythmias (7)(8)(9)(10), whilst there has been no comparison between these two commonly used anesthetics (thiopental and K+X) in an in vivo I/R arrhythmia model.…”

Both Mitochondrial KATP Channel Opening and Sarcolemmal KATP Channel Blockage Confer Protection Against Ischemia/Reperfusion-Induced Arrhythmia in Anesthetized Male Rats

“…The blockage of the K ATP channels by drugs has been reported to be antiarrhythmic 5 and proarrhythmic. 6 K ATP channel openers have also been described as both antiarrhythmic 7 and proarrhythmic agents. 8 Studies researching the effect of the selective K ATP channel modulators are limited.…”

The Effects of Zileuton and Montelukast in Reperfusion-Induced Arrhythmias in Anesthetized Rats

“…Fundamental surgical procedures used in the study were described before by Bozdogan et al 20 Briefly, animals were anaesthetized with thiopental sodium (85 mg/kg IP in a volume of 2 mL/kg) (Abbott, İstanbul, Turkey) and tracheotomy was used for artificial respiration. The left carotid artery was cannulated with polyethylene tubing (0.58 mm × 0.96 mm; Harvard Apparatus, Boston, Massachusetts) to record the arterial blood pressure with a blood pressure transducer (SS 13 L; Biopac Systems, Goleta, California).…”

“…The left coronary artery was retightened, and the heart was first perfused through the aorta with 10 mL isotonic sodium chloride solution, followed by 2 mL 96% ethanol for the demarcation of the occluded and nonoccluded myocardium 20 . The nonperfused area that remained red colored (ischemic risk zone) was cut along the epicardially visible border zone from the well-perfused area that seemed white in color (nonischemic myocardium mass).…”