Massive accumulation of myofibroblasts in the critical isthmus is associated with ventricular tachycardia inducibility in post-infarct swine heart

Dhanjal, Tarvinder S., Lellouche, Nicolas, Von Ruhland, Christopher, Abehsira, Guillaume, Edwards, David H., Dubois-Randé, Jean-Luc, Moschonas, Konstantinos, Teiger, Emmanuel, Williams, Alan J. and George, Christopher H. 2017. Massive accumulation of myofibroblasts in the critical isthmus is associated with ventricular tachycardia inducibility in post-infarct swine heart. Journal of the American College of Cardiology: Clinical Electrophysiology 3 (7) , pp. 703-714. 10.1016/j.jacep.2016.11.010

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Abstract

Objectives In this study the authors determined the extent of cellular infiltration and dispersion, and regional vascularization in electrophysiologically (EP) defined zones in post–myocardial infarction (MI) swine ventricle. Background The critical isthmus (CI) in post-MI re-entrant ventricular tachycardia (VT) is a target for catheter ablation. In vitro evidence suggests that myofibroblasts (MFB) within the scar border zone (BZ) may increase the susceptibility to slow conduction and VT, but whether this occurs in vivo remains unproven. Methods Six weeks after mid–left anterior descending coronary artery occlusion, EP catheter-based mapping was used to assess susceptibility to VT induction. EP data were correlated with detailed cellular profiling of ventricular zones using immunohistochemistry and spatial distribution analysis of cardiomyocytes, fibroblasts, MFB, and vascularization. Results In pigs with induced sustained monomorphic VT (mean cycle length: 353 ± 89 ms; n = 6) the area of scar that consisted of the BZ (i.e., between the normal and the low-voltage area identified by substrate mapping) was greater in VT-inducible hearts (iVT) than in noninducible hearts (non-VT) (p < 0.05). Scar in iVT hearts was characterized by MFB accumulation in the CI (>100 times that in normal myocardium and >5 times higher than that in the BZ in non-VT hearts) and by a 1.7-fold increase in blood vessel density within the dense scar region extending towards the CI. Sites of local abnormal ventricular activity potentials exhibited cellularity and vascularization that were intermediate to the CI in iVT and BZ in non-VT hearts. Conclusions The authors reported the first cellular analysis of the VT CI following an EP-based zonal analysis of iVT and non-VT hearts in pigs post-MI. The data suggested that VT susceptibility was defined by a remarkable number of MFB in the VT CI, which appeared to bridge the few remaining dispersed clusters of cardiomyocytes. These findings define the cellular substrate for the proarrhythmic slow conduction pathway.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > R Medicine (General)
ISSN:	2405-5018
Date of First Compliant Deposit:	24 May 2018
Date of Acceptance:	17 November 2016
Last Modified:	22 Oct 2023 10:49
URI:	https://orca.cardiff.ac.uk/id/eprint/111732

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