The electrophysiology of rabbit hearts with left ventricular hypertrophy under normal and ischaemic conditions

Hicks, Martin N.; McIntosh, M.A.; Kane, Kathleen A.; Rankin, Andrew C.; Cobbe, Stuart M.

doi:10.1016/s0008-6363(95)00065-8

Cited by 12 publications

(3 citation statements)

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“… 44 In the present study, ischaemic ERP shortening in HCM always occurred concomitantly with enhanced APD shortening (see Supplementary material online , Figure S10 ). Indeed, both enhanced ischaemic ERP 45 , 46 and APD 21 , 45–47 shortening, and APD dispersion, 48 have been reported in various hypertrophied animal models. Interestingly, one study instead reported enhanced ischaemic ERP prolongation in hypertrophied rats.…”

Section: Discussionmentioning

confidence: 98%

Mechanisms of ischaemia-induced arrhythmias in hypertrophic cardiomyopathy: a large-scale computational study

Coleman,

Doste,

Ashkir

et al. 2024

Cardiovascular Research

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Aims Lethal arrhythmias in hypertrophic cardiomyopathy (HCM) are widely attributed to myocardial ischaemia and fibrosis. How these factors modulate arrhythmic risk remains largely unknown, especially as invasive mapping protocols are not routinely used in these patients. By leveraging multiscale digital-twin technologies, we aim to investigate ischaemic mechanisms of increased arrhythmic risk in HCM. Methods and Results Computational models of human HCM cardiomyocytes, tissue and ventricles were used to simulate outcomes of phase 1A acute myocardial ischaemia. Cellular response predictions were validated with patch-clamp studies of human HCM cardiomyocytes (n=12 cells, N=5 patients). Ventricular simulations were informed by typical distributions of subendocardial/transmural ischaemia as analysed in perfusion scans (N=28 patients). S1-S2 pacing protocols were used to quantify arrhythmic risk for scenarios in which regions of septal obstructive hypertrophy were affected by (i) ischaemia, (ii) ischaemia and impaired repolarisation, and (iii) ischaemia, impaired repolarisation, and diffuse fibrosis. HCM cardiomyocytes exhibited enhanced action potential and abnormal effective refractory period shortening to ischaemic insults. Analysis of c.a. 75,000 re-entry induction cases revealed that the abnormal HCM cellular response enabled establishment of arrhythmia at milder ischaemia than otherwise possible in healthy myocardium, due to larger refractoriness gradients that promoted conduction block. Arrhythmias were more easily sustained in transmural than subendocardial ischaemia. Mechanisms of ischaemia-fibrosis interaction were strongly electrophysiology dependent. Fibrosis enabled asymmetric re-entry patterns and break-up into sustained ventricular tachycardia. Conclusions HCM ventricles exhibited an increased risk to non-sustained and sustained re-entry, largely dominated by an impaired cellular response and deleterious interactions with the diffuse fibrotic substrate.

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Section: Discussionmentioning

confidence: 98%

Mechanisms of ischaemia-induced arrhythmias in hypertrophic cardiomyopathy: a large-scale computational study

Coleman,

Doste,

Ashkir

et al. 2024

Cardiovascular Research

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“…The results related to the depolarization phase of AP are not consistent. On one hand, no differences in resting membrane potential, the action potential upstroke velocity, or amplitude are documented [47,48]; on the other hand, significant changes are reported [39,49,50]. Also, there is not a consistent pattern in conduction velocity changes of hypertrophied cardiomyocytes [51,52].…”

Section: Left Ventricular Hypertrophymentioning

confidence: 97%

Missing Link Between Molecular Aspects of Ventricular Arrhythmias and QRS Complex Morphology in Left Ventricular Hypertrophy

Bachárová

2019

IJMS

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The aim of this opinion paper is to point out the knowledge gap between evidence on the molecular level and clinical diagnostic possibilities in left ventricular hypertrophy (LVH) regarding the prediction of ventricular arrhythmias and monitoring the effect of therapy. LVH is defined as an increase in left ventricular size and is associated with increased occurrence of ventricular arrhythmia. Hypertrophic rebuilding of myocardium comprises interrelated processes on molecular, subcellular, cellular, tissue, and organ levels affecting electrogenesis, creating a substrate for triggering and maintaining arrhythmias. The knowledge of these processes serves as a basis for developing targeted therapy to prevent and treat arrhythmias. In the clinical practice, the method for recording electrical phenomena of the heart is electrocardiography. The recognized clinical electrocardiogram (ECG) predictors of ventricular arrhythmias are related to alterations in electrical impulse propagation, such as QRS complex duration, QT interval, early repolarization, late potentials, and fragmented QRS, and they are not specific for LVH. However, the simulation studies have shown that the QRS complex patterns documented in patients with LVH are also conditioned remarkably by the alterations in impulse propagation. These QRS complex patterns in LVH could be potentially recognized for predicting ventricular arrhythmia and for monitoring the effect of therapy.

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“…After 30 minutes of ischemia, ERP is approximately 40% longer than APD 90 . 7 Therefore, the fact that the slope of the APD restitution curve becomes flatter after development of ischemia does not necessarily mean the ERP restitution curve, which is more closely related to conduction block, undergoes the same change in slope.…”

Section: Editorial Commentmentioning

confidence: 99%

Types of Ventricular Fibrillation:

Ideker

Rogers

Huang³

2004

Cardiovasc electrophysiol

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Editorial CommentVentricular fibrillation (VF) has been considered to be caused by totally disorganized electrical activity, 1 but evidence accumulating for over half a century suggests different degrees and types of organization exist during VF. As VF continues, it progresses through different stages. Wiggers divided this time course into four stages based on high-speed cinematography 1,2 while Huang et al. divided it into five stages based on electrical activation mapping. 3 In addition to changes in VF over time, the Cedar Sinai-UCLA group has reported two distinct types of VF. [4][5][6] In type I VF, the activation rate is rapid, reentry is uncommon and short lived, and activation wavefronts follow constantly changing pathways with little repetition. Although the conduction velocity (CV) restitution curve is flat and the action potential duration (APD) restitution curve determined by pacing is steep, the authors believe this steep APD restitution curve is responsible for conduction block during type I VF. In type II VF, the activation rate is slower and many of the activation fronts are large and follow similar pathways. Whereas the APD restitution slope is flat, excitability is reduced and the CV restitution curve is broad. The authors believe this broad CV restitution is responsible for conduction block in type II VF.The same authors state that type I VF is consistent with VF Maintenance by wandering wavelets, whereas type II VF is consistent with VF maintenance by a mother rotor. 5 They also reported that the two types of VF can occur at different times in the same heart, either through reducing excitability by giving a high dose of the drug D600, which causes type II VF in a heart that exhibited type I VF before the drug, 4 or through changes in VF over time with the first two of Wiggers' stages representing type I VF and the later stages type II VF. 5 In this issue of the Journal, the same group reports that both types of VF can coexist simultaneously in different regions of the same heart. 6 They performed optical mapping in isolated, perfused rabbit hearts in which a region of ischemia was created by coronary occlusion. The ischemic zone was identified by shortening of the APD, whereas the APD was normal or lengthened in the nonischemic zone. These investigators found that type I VF was present in the nonischemic zone, whereas type II VF was present simultaneously in the ischemic zone. They reported that, after occlusion, the slope of the APD restitution curve decreased in the ischemic region consistent with type II VF, whereas the slope increased in the nonischemic region, consistent with type I VF. They also found that the incidence of conduction block was increased in all portions of the mapped myocardium after occlusion, i.e., in the ischemic zone, in the nonischemic zone, and in the border zone encompassing the boundary between these two zones. Based on these findings, the authors concluded that changes in both the ischemic and the nonischemic zones are proarrhythmic and that these two zones play ...

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The electrophysiology of rabbit hearts with left ventricular hypertrophy under normal and ischaemic conditions

Cited by 12 publications

References 0 publications

Mechanisms of ischaemia-induced arrhythmias in hypertrophic cardiomyopathy: a large-scale computational study

Mechanisms of ischaemia-induced arrhythmias in hypertrophic cardiomyopathy: a large-scale computational study

Missing Link Between Molecular Aspects of Ventricular Arrhythmias and QRS Complex Morphology in Left Ventricular Hypertrophy

Types of Ventricular Fibrillation:

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