Differential Effects of a Segment of Slow Conduction on Reentrant Ventricular Tachycardia in the Rabbit Heart

Haberl, K.; Allessie, Maurits A.

doi:10.1161/01.cir.99.7.949

Cited by 6 publications

(6 citation statements)

References 58 publications

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“…Heptanol is a lipophilic agent known to reversibly inhibit gap junctions and it has been used frequently as an uncoupler to investigate the role of cellular coupling in the induction of re‐entrant arrhythmias 16–18 . It has been shown that heptanol limits myocardial infarct size when infused before ischaemia 19 or during reperfusion 20 .…”

Section: Introductionmentioning

confidence: 99%

Delayed Uncoupling Contributes to the Protective Effect of Heptanol Against Ischaemia in the Rat Isolated Heart

Chen

Mao

Fan

et al. 2005

Clin Exp Pharma Physio

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1. It is known that infusion of the gap junction uncoupler heptanol, before ischaemia or during reperfusion, limits myocardial infarct size. However, whether this cardiac effect is linked to the effect of heptanol on communication across gap junctions has not been elucidated. The aims of the present study were to examine the effect of heptanol on infarct size, arrhythmias and myocardial tissue resistance and to assess whether changes in electrical coupling correlate with cardiac protection. 2. Rat isolated, perfused hearts were subjected to a 24 min infusion of heptanol (0.05, 0.1, 0.5 or 1.0 mmol/L) followed by 20 min regional ischaemia and 60 min reperfusion, or by 70 min global no-flow ischaemia. The effective refractory period, action potential and conduction velocity were measured in papillary muscles from the right ventricle. Heptanol markedly decreased arrhythmia scores during ischaemia and reperfusion, as well as reducing infarct size to a degree similar to that induced by ischaemic preconditioning. In the prolonged ischaemia model, heptanol delayed the onset of uncoupling, increased time to plateau and decreased the maximal rate of uncoupling during ischaemia. Ischaemic preconditioning had similar effects on these parameters. In papillary muscle, heptanol reduced the conduction velocity of the action potential in a dose-dependent manner, but had no significant effect on resting potential, action potential amplitude, action potential duration, maximal upstroke of depolarization or effective refractory period. 3. These results demonstrate that treatment with the gap junction uncoupler heptanol confers cardioprotection against ischaemia and this effect is related to delayed electrical uncoupling during prolonged ischaemia.

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Section: Introductionmentioning

confidence: 99%

Delayed Uncoupling Contributes to the Protective Effect of Heptanol Against Ischaemia in the Rat Isolated Heart

Chen

Mao

Fan

et al. 2005

Clin Exp Pharma Physio

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“…In both normal dog hearts [6] and the canine model of healed myocardial infarction [7] selective intracoronary infusion of heptanol increases the susceptibility to arrhythmias, consistent with altered cellular coupling being an important risk factor for arrhythmogenesis [37]. Furthermore, in perfused rabbit heart epicardial preparations the arrhythmias produced by heptanol are likely to be re-entrant ventricular tachycardias (VT) [14]. Whilst heptanol is relatively selective in its actions on gap junctions (e.g.…”

Section: Introductionmentioning

confidence: 99%

The effect of heptanol on the electrical and contractile function of the isolated, perfused rabbit heart

Keevil

Huang

Chau

et al. 2000

Pflugers Arch - Eur J Physiol

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Changes in cardiac gap junction expression, such as those following myocardial infarction and produced in connexin knockout mice, are associated with a predisposition to arrhythmias. The present experiments investigated the effects of heptanol, a reversible gap junction inhibitor, on isolated Langendorff-perfused rabbit hearts. The introduction and withdrawal of heptanol inhibited both pressure generation and electrical conduction. These effects were completely reversible. Possible mechanisms for these findings were investigated through measurement of the concentration dependence of heptanol's effects upon conduction velocity and repolarization duration. Low concentrations of heptanol (less than 0.3 mM) caused small but significant increases in the delay between the stimulus (delivered to the basal septum) artefact and local activation of the left ventricle, as measured from bipolar electrogram (BEG) recordings. There was a steep increase in the latency between stimulus and left-ventricular activation at concentrations of heptanol above 0.3 mM. These findings are explicable by earlier reports of heptanol actions on gap junctions in vitro and modelling studies of the effects of reduced gap junction conductance on conduction velocity. Heptanol decreased repolarization duration, measured from the activation recovery interval (ARI) of BEGs, and monophasic action potential duration at 70% repolarization (MAPD70). Heptanol also reduced left-ventricular developed pressure (LVDP), and the maximum rates of contraction and relaxation of the left ventricle; these effects were concentration dependent and reversible. However, changes in ARIs, LVDP and the maximum rates of change of pressure lacked the steep response to 0.3-1.0 mM heptanol shown by the latency. These other effects are therefore likely to be mediated by cellular targets other than gap junctions. Perfusion of hearts with heptanol was also associated with a high incidence of arrhythmias. During premature stimulation protocols arrhythmias could be induced in hearts perfused with 0.1-0.3 mM heptanol but not at higher concentrations. This suggests that there is a critical range of slowed conduction that permits the development of re-entrant arrhythmias in the normal heart, although the effects of heptanol on repolarization duration may also contribute to its pro-arrhythmic activity.

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“…Similar to patients with ischemic cardiomyopathy, patients in whom no sites with IPs were identified during mapping of VT had a high probability of recurrent VT 3 . Major complications associated with the failure to eliminate inducible VTs by ablation have been described previously in patients with nonischemic cardiomyopathy 9–11 . It is possible that systematic epicardial mapping in all patients would have revealed IPs in some of the patients who did not have endocardial IPs.…”

Section: Discussionmentioning

confidence: 88%

Isolated Potentials and Pace‐Mapping as Guides for Ablation of Ventricular Tachycardia in Various Types of Nonischemic Cardiomyopathy

Kühne

Abrams

Sarrazin

et al. 2010

Cardiovasc electrophysiol

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Differential Effects of a Segment of Slow Conduction on Reentrant Ventricular Tachycardia in the Rabbit Heart

Cited by 6 publications

References 58 publications

Delayed Uncoupling Contributes to the Protective Effect of Heptanol Against Ischaemia in the Rat Isolated Heart

Delayed Uncoupling Contributes to the Protective Effect of Heptanol Against Ischaemia in the Rat Isolated Heart

The effect of heptanol on the electrical and contractile function of the isolated, perfused rabbit heart

Isolated Potentials and Pace‐Mapping as Guides for Ablation of Ventricular Tachycardia in Various Types of Nonischemic Cardiomyopathy

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