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

Gonca, Ersöz; Bozdoğan, Ömer

doi:10.1177/1074248410372925

Cited by 17 publications

(22 citation statements)

References 35 publications

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“…Additionally, reperfusion injury may cause the release of metabolites, which may affect resting membrane potential, intracellular Ca 2+ concentrations and ion channel function [44,45]. In the present study, we observed that GA decreases the incidence of I/R injury-induced arrhythmia.…”

Section: Discussionsupporting

confidence: 63%

Glycyrrhetinic Acid Protects the Heart from Ischemia/Reperfusion Injury by Attenuating the Susceptibility and Incidence of Fatal Ventricular Arrhythmia During the Reperfusion Period in the Rat Hearts

Yang

Jin

et al. 2015

Cell Physiol Biochem

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Background/Aims: Licorice has been used to treat many diseases, including palpitations, in both Eastern and Western societies for thousands of years. It has been reported that glycyrrhetinic acid (GA), an aglycone saponin extracted from licorice root, exerts protective effects on the cardiovascular system, limits infarct sizes and protects against the development of arrhythmia. However, the mechanisms underlying the effects of glycyrrhetinic acid on the cardiovascular system remain poorly understood. This study aimed to determine the mechanisms underlying the protective effects of GA against lethal cardiac arrhythmias induced via ischemia-reperfusion in rat hearts, and to examine its electropharmacological properties. Materials and Methods: Anesthetized rats were divided into control (CTL), GA5, GA10, and GA20 groups. GA was administered intravenously 15 min before the occlusion of the left anterior descending coronary artery, at dosages of 5, 10 and 20 mg/kg, respectively. Single ventricular myocytes were isolated using enzymolysis. The whole-cell patch clamp technique was utilized to record Ica, L, Ito and action potentials (APs). Results: During reperfusion, the incidence of ventricular fibrillation (VF) was decreased in each of the groups compared with the CTL group (p<0.05). The ventricular tachycardia (VT)/VF score was significantly decreased in the GA20 group. Action potential durations (APDs) were prolonged by GA; both L-type calcium current (Ica-L) and transient outward potassium current (Ito) were blocked in a concentration-dependent manner by GA. Conclusion: These results suggest that GA attenuates both the susceptibility to and the incidence of fatal ventricular arrhythmia during reperfusion in rat hearts via the prolongation of the APD and the inhibition of both Ica-L and Ito. GA appears to be a promising antiarrhythmic agent in the setting of ischemia/reperfusion.

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Section: Discussionsupporting

confidence: 63%

Glycyrrhetinic Acid Protects the Heart from Ischemia/Reperfusion Injury by Attenuating the Susceptibility and Incidence of Fatal Ventricular Arrhythmia During the Reperfusion Period in the Rat Hearts

Yang

Jin

et al. 2015

Cell Physiol Biochem

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Gonca¹

2015

Turk J Med Sci

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Background/aim: To investigate the influence of thiopental (85 mg/kg, intraperitoneally (ip)), and ketamine+xylazine (ketamine 75 mg/kg and xylazine 8 mg/kg, ip) anesthesia on the incidence and duration of ischemia/reperfusion-induced arrhythmias.Materials and methods: Myocardial ischemia was induced by a 6-min ligation of the left anterior descending coronary artery, followed by a 6-min reperfusion. Measurements were taken of the incidence and duration of ventricular arrhythmias, the mean arterial blood pressure and heart rate, and the pressure rate-product (as an index of myocardial oxygen consumption). Results:The arrhythmia score and the incidence of ventricular fibrillation and tachycardia were significantly decreased in the ketamine+xylazine-anesthetized rats compared with the thiopental-anesthetized group (arrhythmia score: 2.0 ± 2.1 versus 3.7 ± 1.2, P < 0.05). The heart rate was significantly lower in the ketamine+xylazine group during the entire experiment, whilst the pressure-rate product was also significantly lower in the ketamine+xylazine group at different time points of the ischemia and reperfusion periods. Conclusion:Ketamine+xylazine anesthesia has a strong antiarrhythmic effect and an apparent depressive action on the heart rate and the myocardial oxygen consumption index. Therefore, ketamine+xylazine anesthesia is not appropriate for the evaluation of possible antiarrhythmic agents. Thiopental anesthesia is preferable to ketamine+xylazine anesthesia in the in vivo ischemia-reperfusion arrhythmia model.

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“…Previous studies have shown that ATP-sensitive K + channels (K ATP ) play an important role in protecting the heart from ischemic-reperfusion injury [4,5]. The neuroprotective effects of K ATP channels are involved in the mechanisms of many agents that have been shown to be capable of protecting the brain [6].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of 17β-estradiol associate with KATP in rat brain

Zhang

Xia

et al. 2012

NeuroReport

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Previous studies have indicated that estrogen protects the brain from ischemic damage and regulates K(ATP) channel activity; the present study was designed to address the involvement of K(ATP) channels in the neuroprotective effects of estrogen in focal cerebral ischemia: in experiment 1, K(ATP) mRNA and protein in the cortices of rats were compared among groups of ovariectomized rats (Ovx-1), Sham-operated rats (Sham-1), and ovariectomized rats administered 17β-estradiol (Estr-1). In experiment 2, neurobehavioral scores and infarct volume of rats were evaluated after middle cerebral artery occlusion in ovariectomized rats (Ovx-2), Sham-operated rats (Sham-2), ovariectomized female rats administered 17β-estradiol (Estr-2), and ovariectomized rats administered both 17β-estradiol and stereotactic injections of glibenclamide (Estr+G). Our results showed that the Kir6.2 and SUR1 mRNA and protein levels in the brain cortices of female ovariectomized rats were lower than those in Sham rats. However, the expression levels of Kir6.2 and SUR1 in brain cortices of ovariectomized rats recovered after supplementation with 17β-estradiol. The protective effects of 17β-estradiol were abolished by glibenclamide, a K(ATP) channel blocker. This indicates that estradiol significantly upregulates the expression of K(ATP) channel subunits and channel activity in the brain cortices of ovariectomized rats. This regulation is associated with the neuroprotective effects of estradiol.

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

Cited by 17 publications

References 35 publications

Glycyrrhetinic Acid Protects the Heart from Ischemia/Reperfusion Injury by Attenuating the Susceptibility and Incidence of Fatal Ventricular Arrhythmia During the Reperfusion Period in the Rat Hearts

Glycyrrhetinic Acid Protects the Heart from Ischemia/Reperfusion Injury by Attenuating the Susceptibility and Incidence of Fatal Ventricular Arrhythmia During the Reperfusion Period in the Rat Hearts

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

Neuroprotective effects of 17β-estradiol associate with KATP in rat brain

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