Relevance of Inter- and Intraventricular Electrical Dispersion to Arrhythmogenesis in Normal and Ischaemic Rabbit Myocardium: A Study with Cromakalim, 5-Hydroxydecanoate and Glibenclamide

Wołk, Robert; Cobbe, Stuart M.; Kane, Kathleen A.; Hicks, Martin N.

doi:10.1097/00005344-199902000-00022

Cited by 21 publications

(9 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…), a difference which is attributed to the greater expression of I K1 , the inward rectifier K + current, in LV cells . In rabbit heart, the published data on interventricular difference in repolarization are quite inconclusive, with APD shown to be similar in both ventricular chambers, or to exhibit a greater value in either RV or LV myocytes …”

Section: Spatial Repolarization Gradientsmentioning

confidence: 99%

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Osadchii

2017

Acta Physiologica

View full text Add to dashboard Cite

In cardiac patients, life-threatening tachyarrhythmia is often precipitated by abnormal changes in ventricular repolarization and refractoriness. Repolarization abnormalities typically evolve as a consequence of impaired function of outward K currents in cardiac myocytes, which may be caused by genetic defects or result from various acquired pathophysiological conditions, including electrical remodelling in cardiac disease, ion channel modulation by clinically used pharmacological agents, and systemic electrolyte disorders seen in heart failure, such as hypokalaemia. Cardiac electrical instability attributed to abnormal repolarization relies on the complex interplay between a provocative arrhythmic trigger and vulnerable arrhythmic substrate, with a central role played by the excessive prolongation of ventricular action potential duration, impaired intracellular Ca handling, and slowed impulse conduction. This review outlines the electrical activity of ventricular myocytes in normal conditions and cardiac disease, describes classical electrophysiological mechanisms of cardiac arrhythmia, and provides an update on repolarization-related surrogates currently used to assess arrhythmic propensity, including spatial dispersion of repolarization, activation-repolarization coupling, electrical restitution, TRIaD (triangulation, reverse use dependence, instability, and dispersion), and the electromechanical window. This is followed by a discussion of the mechanisms that account for the dependence of arrhythmic vulnerability on the location of the ventricular pacing site. Finally, the review clarifies the electrophysiological basis for cardiac arrhythmia produced by hypokalaemia, and gives insight into the clinical importance and pathophysiology of drug-induced arrhythmia, with particular focus on class Ia (quinidine, procainamide) and Ic (flecainide) Na channel blockers, and class III antiarrhythmic agents that block the delayed rectifier K channel (dofetilide).

show abstract

Section: Spatial Repolarization Gradientsmentioning

confidence: 99%

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Osadchii

2017

Acta Physiologica

View full text Add to dashboard Cite

show abstract

“…It should be noted, however, that in these animals glibenclamide significantly reduced both the exercise-and reactive-hyperemia-induced increases in coronary blood flow as well as depressed ventricular function (large reductions in left ventricular dP/dt maximum) [Billman et al, 1993[Billman et al, , 1998]. In the isolated working rabbit heart, glibenclamide provoked an immediate decrease in coronary blood flow, reducing forward flow to zero [Wolk et al, 1999]. Thus, glibenclamide has potent vasoconstrictor effects because of the inhibition of ATP-sensitive potassium channels located on the coronary vascular smooth muscle.…”

Section: Atp-sensitive Potassium Channel Antagonists: Ischemia-selectmentioning

confidence: 99%

Animal models of lethal arrhythmias

Billman

2002

Drug Development Research

View full text Add to dashboard Cite

Sudden cardiac death resulting from ventricular tachyarrhythmias remains the leading cause of death in industrially developed countries, accounting for between 300,000 and 500,000 deaths each year in the United States. Yet, despite the enormity of this problem, the development of safe and effective antiarrhythmic agents remains elusive. Indeed, several class I (encainide and flecainide) and class III (dsotalol) drugs have actually been shown to increase, rather than decrease, the risk of arrhythmic death in patients recovering from myocardial infarction. The identification of effective antiarrhythmic agents is critically dependent on the use of appropriate animal models of human disease. In particular, myocardial ischemia may be an important determinant for the development of the life-threatening ventricular arrhythmias. For example, preclinical studies demonstrate that many drugs that prevent arrhythmias induced by programmed electrical stimulation fail to prevent ventricular fibrillation provoked by ischemia in the same animals. Thus, one would predict that animal models in which lethal arrhythmias are induced by myocardial ischemia would be the most effective tools for the identification of potential antiarrhythmic medications. This review first evaluates several animal models of lethal ventricular arrhythmias with particular emphasis placed on canine models. Then it closes with a brief discussion of ATP-sensitive potassium-channel antagonists as an example of antiarrhythmic drugs that may act selectively on the ischemic myocardium. Drug Dev. Res. 55:59-72, 2002.

show abstract

“…When K ATP channels open during ischaemia, resultant dispersion of refractoriness and slowing of conduction could predispose to reentrant arrhythmias; by preventing these effects, K ATP channel blockade could be anti-arrhythmic and protective. In fact, some studies have indicated that K ATP channel blockers reduce the propensity for ischaemic arrhythmias [12,13], while K ATP channel openers facilitate induction of ventricular fibrillation [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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

Reiter

et al. 2008

Diabetologia

View full text Add to dashboard Cite

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.

show abstract

Relevance of Inter- and Intraventricular Electrical Dispersion to Arrhythmogenesis in Normal and Ischaemic Rabbit Myocardium: A Study with Cromakalim, 5-Hydroxydecanoate and Glibenclamide

Cited by 21 publications

References 34 publications

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Animal models of lethal arrhythmias

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

Contact Info

Product

Resources

About