In isolated failing human hearts, baseline AVJ rhythm (29 bpm) was accelerated by isoproterenol to 69 bpm and decreased by acetylcholine to 18 bpm, with shifts in pacemaker location.
How does autonomic stimulation modulate the anatomic localization and pacemaker properties of the atrioventricular junction in failing human hearts?
In failing human hearts, the AVJ pacemaker is located in the nodal-His or His bundle regions and its location and rate are dynamically modulated by autonomic stimulation.
BACKGROUND: The structure-function relationship in the atrioventricular junction (AVJ) of various animal species has been investigated in detail; however, less is known about the human AVJ. In this study, we performed high-resolution optical mapping of the human AVJ (n = 6) to define its pacemaker properties and response to autonomic stimulation. METHODS AND RESULTS: Isolated, coronary-perfused AVJ preparations from failing human hearts (n = 6, 53 ± 6 years) were optically mapped using the near-infrared, voltage-sensitive dye, di-4-ANBDQBS, with isoproterenol (1 μmol/L) and acetylcholine (1 μmol/L). An algorithm detecting multiple components of optical action potentials was used to reconstruct multilayered intramural AVJ activation and to identify specialized slow and fast conduction pathways (SP and FP). The anatomic origin and propagation of pacemaker activity was verified by histology. Spontaneous AVJ rhythms of 29 ± 11 bpm (n = 6) originated in the nodal-His region (n = 3) and/or the proximal His bundle (n = 4). Isoproterenol accelerated the AVJ rhythm to 69 ± 12 bpm (n = 5); shifted the leading pacemaker to the transitional cell regions near the FP and SP (n = 4) and/or coronary sinus (n = 2); and triggered reentrant arrhythmias (n = 2). Acetylcholine (n = 4) decreased the AVJ rhythm to 18 ± 4 bpm; slowed FP/SP conduction leading to block between the AVJ and atrium; and shifted the pacemaker to either the transitional cell region or the nodal-His region (bifocal activation). CONCLUSIONS: We have demonstrated that the AVJ pacemaker in failing human hearts is located in the nodal-His region or His bundle regions and can be modified with autonomic stimulation. Moreover, we found that both the FP and SP are involved in anterograde and retrograde conduction.
Fedorov et al. (Tue,) conducted a other in Failing human hearts (n=6). Isoproterenol and acetylcholine vs. Baseline was evaluated on AVJ rhythm and pacemaker location. In isolated failing human hearts, baseline AVJ rhythm (29 bpm) was accelerated by isoproterenol to 69 bpm and decreased by acetylcholine to 18 bpm, with shifts in pacemaker location.