Shift in the pattern of autonomic atrial innervation in subjects with persistent atrial fibrillation

Background: Atrial fibrillation (AF) is a multifactorial disease of the atria.

Objective: We studied the differences in the atrial autonomic innervation pattern in subjects with AF compared with sinus rhythm (SR).

Methods: Preparation of postmortem isolated hearts of subjects with documented persistent AF (group A) and SR (group B) included: (1) histological sectioning of predefined areas and quantification of nerve density, and (2) differentiation using immunohistochemistry in adrenergic (sympathetic, tyrosine-hydroxylase antibody), cholinergic (parasympathetic, choline-acetyltransferase antibody) and mixed (adrenergic and cholinergic staining) nerves.

Results: Characteristics of subjects in group A (N = 15) and group B (N = 24) did not differ. The mean overall nerve density was similar between groups (A: 0.31 ± 0.25/mm(2); B: 0.35 ± 0.25/mm(2); P = .87). Nerve density appeared higher in the region of the pulmonary vein ostia and antrum (group A: 0.38 ± 0.21/mm(2); group B: 0.32 ± 0.19/mm(2),) compared with other locations of the right and left atrium. A total of 2,224 (group A: 685; group B: 1539) nerves were differentiated using immunohistochemistry. There was a high degree of colocalization of adrenergic and cholinergic nerves (group A: 80% mixed staining, group B: 69% mixed staining). In group A hearts there was a significantly lower density of predominantly cholinergic nerves (0.025 ± 0.052/mm(2) vs. 0.058 ± 0.099/mm(2); P = .008) and a higher density of nerves containing adrenergic components (0.24 ± 0.18/mm(2) vs. 0.18 ± 0.17/mm(2), P = .046).

Conclusion: Overall autonomic nerve density did not differ between atria with persistent AF compared with SR. On a morphological level, we detected a shift toward a lower density of cholinergic nerves and a higher density of nerves containing adrenergic components in AF subjects.