Atrioventricular conduction disturbances during hypoxia. Possible role of adenosine in rabbit and guinea pig heart.
Adenosine and related compounds can produce atrioventricular (A-V) conduction block. Similar conduction disturbances are observed in myocardial hypoxia. To investigate the possibility that adenosine might be causally involved in hypoxic conduction disturbances, we measured A-V conduction times, subdivided into atrial-to-His bundle (A-H) and His bundle-to-ventricular (H-V) intervals, with extracellular electrodes in isolated rabbit and guinea pig hearts perfused with modified Krebs-Henseleit solution. Adenosine produced dose-dependent prolongation of A-V conduction time in both species, although guinea pig hearts responded to lower doses (10(-7) M) and showed a steeper dose-response relationship than rabbit hearts. Higher adenosine doses produced second-degree heart block in both species. Conduction delay was confined to the A-H interval, implicating action on A-V node cells. Further investigation of guinea pig hearts revealed a specific antagonism towards adenosine's effects by 10(-5) M aminophylline. Conduction disturbances produced by acetylcholine or MnCl2 were unaffected by aminophylline as were adenosine's effects by atropine. Perfusion with hypoxic perfusate caused A-V conduction delays and second-degree block in guinea pigs hearts. This effect was dramatically attenuated by aminophylline. We conclude that endogenously released adenosine may cause at least some of the A-V conduction disturbances associated with acute myocardial hypoxia. Furthermore, methylxanthines may prove to be of therapeutic value in combatting such disturbances in a clinical setting.
D000241:Adenosine / Q000494:pharmacology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001283:Atrioventricular Node / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D006327:Heart Block / Q000209:etiology; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D011817:Rabbits; D013997:Time Factors
D000628:Aminophylline; D000241:Adenosine