Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous evidence in animal models suggests that the gap junction (GJ) adjacent nanodomain – perinexus – is a site capable of independent intercellular communication via ephaptic transmission. Perinexal expansion is associated with slowed conduction and increased ventricular arrhythmias in animal models, but has not been studied in human tissue. The purpose of this study was to characterize the perinexus in humans and determine if perinexal expansion associates with AF.Methods: Atrial appendages from 39 patients (pts) undergoing cardiac surgery were fixed for immunofluorescence and transmission electron microscopy (TEM). Intercalated disk distribution of the cardiac sodium channel Nav1.5, its β1 subunit, and connexin43 (C×43) was determined by confocal immunofluorescence. Perinexal width (Wp) from TEM was manually segmented by two blinded observers using ImageJ software.Results: Nav1.5, β1, and C×43 are co-adjacent within intercalated disks of human atria, consistent with perinexal protein distributions in ventricular tissue of other species. TEM revealed that the GJ adjacent intermembrane separation in an individual perinexus does not change at distances greater than 30 nm from the GJ edge. Importantly, Wp is significantly wider in patients with a history of AF than in patients with no history of AF by approximately 3 nm, and Wp correlates with age (R = 0.7, p < 0.05).Conclusion: Human atrial myocytes have voltage-gated sodium channels in a dynamic intercellular cleft adjacent to GJs that is consistent with previous descriptions of the perinexus. Further, perinexal width is greater in patients with AF undergoing cardiac surgery than in those without.

Atherosclerotic lesions commonly develop at arterial branch sites, which are also the sites of high arterial Intramural stress produced by Intralumlnal pressure. We Investigated the effect of reduced Intramural stress on the development of atherosclerotic lesions. We exposed the origin of the left renal artery In five rabbits and the aortic bifurcation in another five, lowered the mean arterial pressure to 35 to 45 mm Hg, and poured a dental acrylic liquid around the branch to form a rigid cast When the rabbits recovered and the arterial pressure Increased to normal, the casts prevented the arteries from expanding, thereby maintaining a low Intramural stress. These rabbits plus two unoperated, two sham-operated, two with silicons rubber casts placed at similar pressures, and four with casts placed at 95 mm Hg pressure were given a 2% cholesterol-enriched diet for 7 to 11 weeks, and then their arteries were examined. In all rabbits, atherosclerotic lesions developed at the origins of the Intercostal, cellac, superior mesenterlc, and both renal arteries, and at the aortic bifurcation, with these notable exceptions: no lesions developed at the origins of casted renal arteries or at the casted aortic bifurcations when the cast was placed at a low pressure. Measurements of the diameter and thickness of the aorta In the left renal branch and aortic bifurcation areas, with and without the casts, indicated that there was no significant narrowing of the aortic lumen or thinning of the aorta due to the cast In conclusion, the Inhibition of the development of atherosclerotic lesions appears to be associated with the reduction of arterial Intramural stress. (Arteriosclerosis 8:410-420, July/August 1988)

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