A novel, minimally invasive, segmental myocardial infarction with a clear healed infarct borderzone in rabbits

Abstract

G. A novel, minimally invasive, segmental myocardial infarction with a clear healed infarct borderzone in rabbits. Am J Physiol Heart Circ Physiol 302: H2321-H2330, 2012. First published March 23, 2012 doi:10.1152/ajpheart.00031.2012.-Ventricular arrhythmias in the setting of a healed myocardial infarction have been studied to a much lesser degree than acute and subacute infarction, due to the pericardial scarring, which results from the traditional open-chest techniques used for myocardial infarction (MI) induction. We sought to develop a segmental MI with low perioperative mortality in the rabbit that allows optimal visualization and therefore improved study of the infarction borderzone. Rabbits underwent MI using endovascular coil occlusion of the first obtuse marginal artery. Three weeks postprocedure, we evaluated our model by echocardiography and electrophysiology studies, optical mapping of isolated hearts, and histological studies. Seventeen rabbits underwent the protocol (12 MI and 5 sham) with a 92% survival to completion of the study (11 MI and 5 sham). MI rabbits demonstrated wall motion abnormalities on echocardiography while shams did not. At electrophysiological study, two MI rabbits had inducible ventricular tachycardia and one had inducible ventricular fibrillation. Isolated hearts demonstrated no pericardial scarring with a smooth, easily identifiable infarct borderzone. Optical mapping of the borderzone region showed successful mapping of peri-infarct reentry formation, with ventricular fibrillation inducible in 11 of 11 MI hearts and 1 of 5 sham hearts. We demonstrate successful high resolution mapping in the borderzone, showing delayed conduction in this region corresponding to late deflections in the QRS on ECG. We report the successful development of a minimally invasive MI via targeted coil delivery to the obtuse marginal artery with an exceptionally high rate of procedural survival and an arrhythmogenic phenotype. This model mimics human post-MI on echocardiography, gross pathology, histology, and electrophysiology.arrhythmia; optical mapping; ventricular tachycardia SUDDEN CARDIAC DEATH (SCD) remains a major public health issue constituting an estimated 20% of deaths in industrialized countries (31,40,49). In autopsy series, nearly 50% of SCD victims have had healed myocardial infarction (MI; Refs. 24, 69). The majority of sudden deaths after MI occur due to ventricular tachyarrhythmias (26). Post-MI ventricular arrhythmias have been studied extensively in animal models. The animal studies suggest the epicardial borderzone as a key player in the formation of reentrant ventricular tachyarrhythmias due to changes in tissue structure, ion channels, and gap junctions that slow conduction and generate anisotropy (6,21,22,35,47,65,67). While these studies have greatly enhanced our understanding of post-MI arrhythmias, our understanding of the arrhythmia mechanisms in healed infarct remains limited because most of studies used 5 days postinfarction, not a fully healed post-MI heart. In additio...

The Structure-function remodeling in rabbit hearts of myocardial infarction

“…In general, rabbits had a dominant LCx arterial tree, but a thin and small LAD artery (Ziv et al. 2012), as shown in Figure 1. Given the anatomy of coronary arterial trees, the distal LCx ligation was a standard method to induce myocardial infraction at the apical portion of rabbit LV (Mahaffey et al.…”

“…2002; Ziv et al. 2012). The postmyocardial infarction (post‐MI) rabbit model develops a region of complete akinesis only near the apical region of LV and hence limits the study of HF resulting from myocardial infarction on the anterior and lateral walls of the LV.…”

A novel method of standardized myocardial infarction in aged rabbits

“…In bifurcated, trifurcated, and quadrifurcated rabbits, there was a single vessel that supplies this region, encompassing 30% of the LV. We targeted this region via an endovascular coil embolization technique in 31 young and 61 aged rabbits using the target locations defined in Table 2 (24). Eighty-one percent (25/31) of young and 72% (44/61) of the aged rabbits survived the procedure [P ϭ not significant (NS)].…”

“…MI and coil placement. Our minimally invasive endovascular site-specific infarct methodology has been previously described (24). In brief, a neck incision was performed to isolate the right carotid, and a 4-Fr guide catheter was advanced to the ostia of the desired coronary artery.…”

“…Current infarction models rely on ligation or occlusion of the same artery in each surgical case, regardless of coronary anatomy (5,7,12,24). In rabbits, the most commonly ligated vessels are the left anterior descending (LAD) and left circumflex (LCX) (13,14,16).…”