Effects of calcium, calcium entry blockers and calmodulin inhibitors on atrioventricular conduction disturbances induced by hypoxia.
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.
Anno
T
T
Kodama
I
I
Shibata
S
S
Toyama
J
J
Yamada
K
K
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002746:Chlorpromazine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium; D002746:Chlorpromazine