Vol. 276, Issue 3, H953-H960, March 1999
Modulation of AV nodal and Hisian conduction by changes in
extracellular space
Keith G.
Lurie1,
Atsushi
Sugiyama2,
Scott
McKnite1,
Paul
Coffeen1,
Keitaro
Hashimoto2, and
Shigeru
Motomura3
1 Cardiac Arrhythmia Center,
University of Minnesota, Minneapolis, Minnesota
55455; 2 Department of
Pharmacology, Yamanashi Medical Center, 409-38 Yamanashi;
and 3 Department of
Pharmacology, Hirosaki Medical Center, 036 Hirosaki, Japan
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.
heart; cardiac conduction system; osmolality; adenosine; acetylcholine; heart block; mannitol; atrioventricular
