Autonomic control and innervation of the atrioventricular junctional pacemaker

Background: The main physiologic function of the AV junction is control of timing between atrial and ventricular excitation. However, under pathologic conditions, the AV junction may become the pacemaker of the heart. Unlike the well-characterized sinoatrial node (SAN), autonomic control of the AV junctional pacemaker has not been studied. Objective: The purpose of this study was to characterize the autonomic control and innervation of the AV junctional pacemaker. Methods: The response of rabbit AV junctional pacemaker to autonomic stimulation was investigated using optical mapping, autonomic modulation via subthreshold stimulation (n = 12), and quantitative immunohistochemistry (n = 5), and the density of parasympathetic and sympathetic innervation in optically mapped preparations was quantified. Results: Subthreshold stimulation applied adjacent to the conduction system in the triangle of Koch autonomically modulates the junctional rate, and parasympathetic and sympathetic components can be separated with atropine and the β-blocker nadolol. Subthreshold stimulation increased the rate maximally to 2.1 ± 0.4 times when applied with atropine. Unlike the SAN pacemaker, which shifts significantly in response to autonomic stimulation, the AV junctional pacemaker remains stationary (most often in the inferior nodal extension), moving in only 5% of subthreshold stimulation trials. Staining with tyrosine hydroxylase and choline acetyltransferase revealed heterogeneous innervation within the AV junction. Conclusion: AV junctional rhythm can be autonomically modulated with subthreshold stimulation to produce junctional rates of 145 ± 16 bpm (cycle length 412 ± 29 ms), similar to sinus rates in rabbit. Unlike the SAN, the anatomic location of the AV junctional pacemaker is stable during autonomic modulation.