Modulation of AV nodal and Hisian conduction by changes in extracellular space

Previous studies have demonstrated that the extracellular space (ECS) component of the atrioventricular (AV) node and His bundle region is larger than the ECS in adjacent contractile myocardium. The potential physiological significance of this observation was examined in a canine blood-perfused AV nodal preparation. Mannitol, an ECS osmotic expander, was infused directly into either the AV node or His bundle region. This resulted in a significant dose-dependent increase in the AV nodal or His-ventricular conduction time and in the AV nodal effective refractory period. Mannitol infusion eventually resulted in Wenckebach block (n = 6), which reversed with mannitol washout. The ratio of AV nodal to left ventricular ECS in tissue frozen immediately on the development of heart block (n = 8) was significantly higher in the region of block (4.53 +/- 0.61) compared with that in control preparations (2.23 +/- 0.35, n = 6, P < 0.01) and donor dog hearts (2.45 +/- 0.18, n = 11, P < 0.01) not exposed to mannitol. With lower mannitol rates (10% of total blood flow), AV nodal conduction times increased by 5-10% and the AV node became supersensitive to adenosine, acetylcholine, and carbachol, but not to norepinephrine. We conclude that mannitol-induced changes in AV node and His bundle ECS markedly alter conduction system electrophysiology and the sensitivity of conductive tissues to purinergic and cholinergic agonists.