Molecular Mechanisms of the Inhibitory Effects of Propofol and Thiamylal on Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channels

Kawano, Takashi; Oshita, Shuzo; Takahashi, Akira; Tsutsumi, Yasuo M.; Tomiyama, Yoshinobu; Kitahata, Hiroshi; Kuroda, Yasuhiro; Nakaya, Yutaka

doi:10.1097/00000542-200402000-00024

Cited by 43 publications

(26 citation statements)

References 35 publications

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“…For example, differences between the prior porcine study with HMR 1883 [13] and the present study include the duration of coronary occlusion (20 vs 90 min), the use of autonomic blockade in the present study and the type of anaesthesia (pentobarbital versus α-chloralose). Barbiturate anaesthetics may independently block mitochondrial [45] and sarcolemmal [46] K ATP channels. In the prior porcine study [13], it should also be noted that while HMR 1883 reduced ventricular fibrillation during ischaemia, 5 of 12 treated pigs developed ventricular fibrillation during the first few minutes of reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Thiazolidinedione drugs block cardiac KATP channels and may increase propensity for ischaemic ventricular fibrillation in pigs

Reiter

et al. 2008

Diabetologia

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Aims/hypothesis Opening of ATP-sensitive potassium (K ATP ) channels during myocardial ischaemia shortens action potential duration and is believed to be an adaptive, energy-sparing response. Thiazolidinedione drugs block K ATP channels in non-cardiac cells in vitro. This study determined whether thiazolidinedione drugs block cardiac K ATP channels in vivo. Methods Experiments in 68 anaesthetised pigs determined: (1) effects of inert vehicle, troglitazone (10 mg/kg i.v.) or rosiglitazone (0.1 or 1.0 mg/kg i.v.) on epicardial monophasic action potential (MAP) during 90 min low-flow ischaemia; (2) effects of troglitazone, rosiglitazone or pioglitazone (1 mg/kg i.v.) on response of MAP to intracoronary infusion of a K ATP channel opener, levcromakalim; and (3) effects of inert vehicle, rosiglitazone (1 mg/kg i.v.) or the sarcolemmal K ATP blocker HMR-1098 on time to onset of ventricular fibrillation following complete coronary occlusion. Results With vehicle, epicardial MAP shortened by 44±9 ms during ischaemia. This effect was attenuated to 12±8 ms with troglitazone and 6±6 ms with rosiglitazone (p<0.01 for both vs vehicle), suggesting K ATP blockade. Intracoronary levcromakalim shortened MAP by 38±10 ms, an effect attenuated to 12±8, 13±4 and 9±5 ms during co-treatment with troglitazone, rosiglitazone or pioglitazone (p<0.05 for each), confirming K ATP blockade. During coronary occlusion, median time to ventricular fibrillation was 29 min in pigs treated with vehicle and 6 min in pigs treated with rosiglitazone or HMR-1098 (p<0.05 for both vs vehicle), indicating that K ATP blockade promotes ischaemic ventricular fibrillation in this model. Conclusions/interpretation Thiazolidinedione drugs block cardiac K ATP channels at clinically relevant doses and promote onset of ventricular fibrillation during severe ischaemia.

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Section: Discussionmentioning

confidence: 99%

Thiazolidinedione drugs block cardiac KATP channels and may increase propensity for ischaemic ventricular fibrillation in pigs

Reiter

et al. 2008

Diabetologia

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“…Kalkan et al 24 reported that the activation of K ATP channels seemed to be one of the mechanisms by which propofol induced beneficial effect on contractility of myocardium in hypercholesterolemic rabbit hearts. Kawano et al 25 reported that Values are mean ± SD (n = 6 per group). CoNT = control; P-25 = 25 µM propofol group; P-50 = 50 µM propofol; P-CoNT = control with pacing; P-P25 = 25 µM propofol with pacing; P-P50 = 50 µM propofol with pacing; 5-HD = 5-hydroxydecanoic acid; HMr = HMr1098.…”

Section: Discussionmentioning

confidence: 99%

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Kamada

Kanaya

Hirata

et al. 2008

Can J Anesth/J Can Anesth

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reports of original investigations 595 CAN J ANESTH 55: 9 www.cja-jca.org September, 2008 Purpose: Propofol exerts cardioprotective effects, but the involved mechanisms remain obscure. The present study examines the cardioprotective effects of propofol and its role in cardiac function, including its effect on K ATP channel opening and the inhibition of GSK-3β activity in ischemia-reperfused hearts.Methods: Ischemia-reperfusion (I/R) was produced in isolated guinea pig hearts by stopping coronary perfusion for 25 min, followed by reperfusion. The hearts were incubated for ten minutes, with or without propofol (25 or 50 µM), or for five minutes with 500 µM 5-hydroxydecanoate (a mitochondrial K ATP channel blocker) or 30 µM HMR1098 (sarcolemmal K ATP channel blocker), followed by five minutes with 50 µM propofol before ischemia. Action potentials on the anterior epicardial surface of the ventricle were monitored using a high-resolution charge-coupled device camera system, and at five minutes after reperfusion, GSK-3β phosphorylation at the serine residue, Ser9, was examined.Results: After 35 min of reperfusion, propofol (25 and 50 µM) blunted the adverse effects of I/R and reduced infarct size (P < 0.05). In addition, prior incubation with 5-hydroxydecanoate or HMR1098 had no effect on functional recovery improved by 50 µM propofol. At five minutes after reperfusion, propofol (25 and 50 µM) shortened the duration of the action potential and increased the levels of phospho-GSK-3β (P < 0.05). Conclusions:Propofol enhanced mechanical cardiac recovery and reduced infarct size. The data further suggest that GSK-3β play an important role in propofol cardioprotective actions during coronary reperfusion, but mitochondrial K ATP channels do not. Objectif : Le propofol exerce des effets cardioprotecteurs, mais les mécanismes sous-jacents demeurent obscurs. Cette étude examine les effets cardioprotecteurs du propofol et son rôle dans la fonction cardiaque, notamment son effet sur l'ouverture du canal K ATP et l'inhibition de l'activité du GSK-3β dans des coeurs ischémiques puis reperfusés. Méthode : L'ischémie reperfusion (I/R) a été provoquée dans des coeurs isolés de cobayes en interrompant la per fusion

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“…Electrophysiological experiments have shown that isoflurane may activate K ATP channels at a moderately acidic intracellular pH of 6.8 [16] or facilitate the opening of channels via the activation of protein kinase C [17]. In contrast, our previous patch-clamp experiments indicated that high supraclinical concentrations of propofol directly inhibited the cardiac K ATP -channel activity [18,19]. Ketamine also inhibits recombinant cardiac K ATPchannel activity in a concentration-dependent manner [20].…”

Section: Cardiac K Atp Channel (Sarcolemmal Channel)mentioning

confidence: 80%

Functional roles of ATP-sensitive potassium channel as related to anesthesia

Kawano

2011

J Anesth

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Molecular Mechanisms of the Inhibitory Effects of Propofol and Thiamylal on Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channels

Cited by 43 publications

References 35 publications

Thiazolidinedione drugs block cardiac KATP channels and may increase propensity for ischaemic ventricular fibrillation in pigs

Thiazolidinedione drugs block cardiac KATP channels and may increase propensity for ischaemic ventricular fibrillation in pigs

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Functional roles of ATP-sensitive potassium channel as related to anesthesia

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