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

Atrial fibrillation (AF) is a multifactorial disease of the atria. We studied the differences in the atrial autonomic innervation pattern in subjects with AF compared with sinus rhythm (SR). 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. 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). 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