Effects of
hypoxia on atrioventricular conduction were investigated in the Langendorff-perfused isolated heart of the rabbit with various extracellular
calcium concentrations ([Ca2+]) as well as in the presence of
verapamil,
nifedipine, N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7) and
chlorpromazine. The prolongation of the atrio-His (AH) interval by
hypoxia for 7 min was greater with increasing [Ca2+]o ranging from 1.2 to 5.2 mM. At [Ca2+]o of over 3.2 mM under hypoxic conditions, AH block of the Wenckebach type was observed in some cases.
Verapamil (5 X 10(-8) M) and
nifedipine (5 X 10(-8) M) caused a significant prolongation of AH intervals before
hypoxia. However, the intensity of AH prolongation due to
hypoxia was significantly attenuated in the presence of the
calcium entry blocker, and AH block was not induced even at 3.2 mM [Ca2+]o.
W-7 (5 X 10(-6) M) and
chlorpromazine (10(-6) M) did not affect the AH intervals before
hypoxia. The
hypoxia-induced prolongation of the AH interval or AH block was prevented in the presence of these drugs.
W-5, a
chlorine-deficient derivative of
W-7, showed no protection against
hypoxia-induced AV nodal conduction disturbances. These findings suggest that
hypoxia-induced AV nodal conduction disturbance is explained, at least in part, by the electrical uncoupling of nodal cells, probably due to the
calcium overload. This conduction disturbance is protected by
calcium entry blockers or by
calmodulin inhibitors, but the mode of protective action is not the same for these different categories of drugs.