DISTURBED CONNEXIN43 GAP JUNCTION DISTRIBUTION CORRELATES WITH THE LOCATION OF REENTRANT CIRCUITS IN THE EPICARDIAL BORDER ZONE OF HEALING CANINE INFARCTS THAT CAUSE VENTRICULAR-TACHYCARDIA

Background Slow, nonuniform conduction caused by ahnormal gap-junction al coupling of infarct-related myocardium is thought to be a component of the arrhythmogenic substrate. The hypothesis that changes in gap-j unctional distribution in the epicardial border zone (EBZ) of healing canine infarcts define the locations of reentrant ventricular tachycar dia (VT) circuits was tested by correlating activation maps df the sur viving subepicardial myocardial layer with immunolocalization of the p rincipal gap-junctional protein, connexin43 (Cx43). Methods and Result s The EBZ overlying 4-day-old anterior infarcts in three dogs with ind ucible VT and three noninducible dogs was mapped with a high-resolutio n electrode array and systematically examined by standard histology an d confocal immunolocalization of Cx43. The thickness of the EBZ was si gnificantly less in the hearts with (538 +/- 257 mu m) than without (8 40 +/- 132 mu m; P<.05) VT. At the interface with the underlying necro tic cells, the EBZ myocardium showed a marked disruption of gap-juncti onal distribution, with Cx-43 labeling abnormally arrayed longitudinal ly along the lateral surfaces of the cells. In the BZ of all hearts, t he disrupted Cx43 labeling extended part of the way to the epicardial surface, with the most superficial epicardial myocytes having the norm al transversely orientated pat tern. Only in the hearts with inducible VT did the disorganization extend through the full thickness of the s urviving layer at sites correlating with the location of the central c ommon pathways of the figure-of-8 reentrant VT circuits. Conclusions A ltered gag-junctional distribution is part of the early remodeling of myocardium after infarction, and by defining the location of the commo n central pathway of the reentrant VT circuits, it may be a determinan t of VT susceptibility.