Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel.

Wilde, Arthur A.M.; Escande, Denis; Schumacher, Cees A.; Thüringer, Dominique; Mestre, Michel; Fiolet, J.W.T.; Janse, Michiel J.

doi:10.1161/01.res.67.4.835

Cited by 204 publications

(128 citation statements)

References 48 publications

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“…In conclusion, the stable K ϩ concentrations that we used to create a myocardial heterogeneity correspond to the levels of [K ϩ ] o detected during the first 10 min after coronary occlusion (58,61). This early period of acute ischemia is characterized by a maximum rate of incidence of ventricular arrhythmias (13,33), and the phenomenon described in this work can be one of the scenarios for reentry induction in phase 1a arrhythmias.…”

Section: Discussionsupporting

confidence: 51%

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Sidorov¹,

Uzelac

Wikswo

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Sidorov VY, Uzelac I, Wikswo JP. Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution. Am J Physiol Heart Circ Physiol 301: H209 -H220, 2011. First published May 2, 2011; doi:10.1152/ajpheart.01141.2010.-The heterogeneities of electrophysiological properties of cardiac tissue are the main factors that control both arrhythmia induction and maintenance. Although the local increase of extracellular potassium ([K ϩ ]o) due to coronary occlusion is a well-established metabolic response to acute ischemia, the role of local [K ϩ ]o heterogeneity in phase 1a arrhythmias has yet to be determined. In this work, we created local [K ϩ ]o heterogeneity and investigated its role in fast pacing response and arrhythmia induction. The left marginal vein of a Langendorff-perfused rabbit heart was cannulated and perfused separately with solutions containing 4, 6, 8, 10, and 12 mM of K ϩ . The fluorescence dye was utilized to map the voltage distribution. We tested stimulation rates, starting from 400 ms down to 120 ms, with steps of 5-50 ms. We found that local [K ϩ ]o heterogeneity causes action potential (AP) alternans, 2:1 conduction block, and wave breaks. The effect of [K ϩ ]o heterogeneity on electrical stability and vulnerability to arrhythmia induction was largest during regional perfusion with 10 mM of K ϩ . We detected three concurrent dynamics: normally propagating activation when excitation waves spread over tissue perfused with normal K ϩ , alternating 2:2 rhythm near the border of [K ϩ ]o heterogeneity, and 2:1 aperiodicity when propagation was within the high [K ϩ ]o area. [K ϩ ]o elevation changed the AP duration (APD) restitution and shifted the restitution curve toward longer diastolic intervals and shorter APD. We conclude that spatial heterogeneity of the APD restitution, created with regional elevation of [K ϩ ]o, can lead to AP instability, 2:1 block, and reentry induction. restitution heterogeneity; regional perfusion; optical mapping THE STATIONARY AND DYNAMIC heterogeneities of electrophysiological properties of cardiac tissue play a key role in the induction and maintenance of cardiac arrhythmias (1,10,16,59). Cardiac tissue heterogeneities increase drastically when acute regional ischemia occurs. The early stage of acute ischemia is characterized by abrupt metabolic and electrophysiological changes in the affected area (11). Among them, the more prominent are increased extracellular potassium ([K ϩ ] o ) (25, 26), decreased creatine phosphate (43, 63), elevated intracellular inorganic phosphate (63), acidosis (27, 46), catecholamine release (39), and partial depolarization of transmembrane potential (V m ) (28,36).Since an early change in V m closely relates to [K ϩ ] o accumulation (34, 60), the K ϩ imbalance is considered to be the major factor affecting excitability and is responsible for slow impulse propagation and induction of reentry (51) Although numerous studies have been devoted to investigation ...

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Section: Discussionsupporting

confidence: 51%

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Sidorov¹,

Uzelac

Wikswo

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…That ion is known to treble in concentration in the extracellular space during the preceding 10 min of ischaemia in the rat (Wilde et al, 1990).…”

Section: : Discussionmentioning

confidence: 99%

A KATP channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias

Workman

Mackenzie

Northover

2001

European Journal of Pharmacology

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Low concentrations of certain K ATP openers have been reported to exert a moderate inhibitory effect on arrhythmias during post-ischaemic early myocardial reperfusion, but the accompanying effects on the time course of changes in action potentials in intact hearts have not yet been studied.We report that, in rat isolated hearts reperfusion following 10 min of regional no-flow ischaemia was associated with both an acute, marked, but transient, shortening of ventricular repolarisation (by 63%) during reperfusion, and a high incidence (90%) of ventricular tachyarrhythmias. The K ATP opener Ro 31-6930 [2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide] delivered prior to ischaemia at a relatively low concentration (0.5 µM), significantly reduced the incidence and duration of reperfusion arrhythmias, and prevented the associated acute action potential shortening during reperfusion, each in a glibenclamide (1 µM)-sensitive manner (P<0.05, n=10-15 hearts). This was associated with a moderate, and non-arrhythmogenic, action potential shortening during ischaemia (a potentially "cardioprotective" effect). However, these data highlight the potential harm these drugs may cause, since a higher concentration of Ro 31-6930 caused marked shortening of action potentials and significant pro-arrhythmia during ischaemia. KeywordsATP-sensitive potassium channel; Reperfusion; Isolated heart; Action potential; Ventricular arrhythmias. 1: IntroductionCardiac adenosine triphosphate-sensitive K + (K ATP ) channels, first identified in the sarcolemma (Noma, 1983), and more recently in the mitochondria (Inoue et al., 1991) are thought to remain closed under physiological conditions. It is well recognised that under certain pathological conditions, such as myocardial ischaemia, however, opening of sarcolemmal K ATP channels may contribute to the shortening of action potential duration (Wilde and Janse, 1994; Wilde, 1997). We recently reported (Workman et al., 2000) that in the rat isolated heart, ischaemia in the presence (but not the absence) of pharmacological K ATP activation, caused action potential shortening of a sufficient degree to cause ventricular tachyarrhythmias.It is also recognised that K ATP activation-induced action potential shortening, under certain conditions may help to protect the myocardium from the injury caused by excessive Ca 2+ influx and ATP consumption [see (Grover and Garlid, 2000) for recent review]. Several studies have highlighted the protective effects on the myocardium of pharmacological K ATP activation. In many cases such protection was demonstrated during post-ischaemic reperfusion. For example, K ATP openers have been shown, during reperfusion, to improve recovery of contractile function (Docherty et al., 1997), to restrain the rise in the intracellular Ca 2+ concentration, [Ca 2+ ] i (Behling and Malone, 1995), to enhance the restoration of high energy phosphates (Tanonaka et al., 1999), as well as limiting the extent of myocardial infarction after reperfusion (Grover et al., 1...

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“…However, it has to be emphasized that these experiments were performed in the coronary circulation of animals, and with the use of high glibenclamide concentrations. Moreover, in such experiments glibenclamide has been shown to reduce basal coronary blood flow [37,42]. In contrast, our experiments were performed in the human forearm vascular bed with relatively low glibenclamide concentrations.…”

mentioning

confidence: 99%

“…Indeed, several reports have suggested that only the initial cellular potassium efflux after ischaemia is mediated by activation of K ATP channels [36,37]. The delayed vasodilator response to ischaemia seems predominantly to be mediated by other mechanisms, including the endothelial release of endothelium-derived nitric oxide [38] and prostaglandins [39,40].…”

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confidence: 99%

Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans

et al. 1996

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In 1983, Noma [1] was the first to describe that an outward potassium current increased significantly when guinea pig or rabbit cardiac muscle cells were subjected to hypoxia. This current was caused by the activation of potassium channels, which was independent of the intracellular Ca 2+ concentration, but dependent on the intracellular concentration of adenosine-5 ′-triphosphate ([ATP] i ). These so-called ATPsensitive potassium (K ATP ) channels were suggested to play a cardioprotective role during ischaemia. Later, K ATP channels were also found in skeletal muscle [2], smooth muscle [3] and pancreatic beta cells [4] from animals. In pancreatic beta cells the K ATP channels mediate insulin secretion [5] and are a target for sulphonylurea derivatives in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) [6]. Sulphonylurea derivatives are highly specific in blocking pancreatic and cardiovascular K ATP channels, and Diabetologia (1996Diabetologia ( ) 39: 1562Diabetologia ( -1568 Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans Summary Experimental data show that ATP-sensitive potassium (K ATP ) channels not only occur in pancreatic beta cells, but also in the cardiovascular system, where they mediate important cardioprotective mechanisms. Sulphonylurea derivatives can block the cardiovascular K ATP channels and may therefore interfere with these cardioprotective mechanisms. Therefore, it is of clinical importance to investigate whether sulphonylurea derivatives interact with vascular K ATP channels in humans. Using venous-occlusion strain-gauge plethysmography, we investigated whether ischaemia-induced reactive hyperaemia is reduced by the sulphonylurea derivative glibenclamide in 12 healthy male non-smoking volunteers. Forearm vasodilator responses to three periods of arterial occlusion (2, 5 and 13 min) during concomitant infusion of placebo into the brachial artery were compared with responses during concomitant intra-arterial infusion of glibenclamide (0.33A control study (n = 6) showed that time itself did not change the vasodilator response to ischaemia.Glibenclamide significantly increased minimal vascular resistance (from 2.1 ± 0.1 to 2.3 ± 0.2 arbitrary units, Student's t-test: p = 0.01), and reduced mean forearm blood flow (from 37.5 ± 2.0 to 35.4 ± 2.0 ml ⋅ min -1 ⋅ dl -1 after 13 min occlusion, ANOVA with repeated measures: p = 0.006) and flow debt repayment during the first reperfusion minute (ANOVA with repeated measures: p = 0.04). In contrast, total flow debt repayment was not affected. Infusion of glibenclamide into the brachial artery resulted in local concentrations in the clinically relevant range, whereas the systemic concentration remained too low to elicit hypoglycaemic effects. Our results suggest that therapeutic concentrations of glibenclamide induce a slight but significant reduction in the early and peak vasodilation during reactive hyperaemia.

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Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel.

Cited by 204 publications

References 48 publications

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

A KATP channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias

Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans

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