title: Circadian rhythm of heart rate in the rabbit: prolongation of action potential duration by sustained beta adrenoceptor blockade is not due to associated bradycardia.
abstract: Six litters of six young rabbits were injected intraperitoneally, two per litter, with saline, alinidine, or nadolol once or twice daily for two weeks. In four litters successful radiotransmissions of electrocardiograms were recorded once hourly for four days before and during treatment. Alinidine and nadolol produced an overall mean bradycardia in comparison with saline treated animals, the effect of alinidine exceeding that of nadolol. At 48-70 hours after the end of treatment the hearts were used for in vitro electrophysiological study. Nadolol, but not alinidine, induced a prolongation of action potential duration compared with that of saline treated littermates in both atrial and ventricular muscle. An incidental observation was that heart rate in the rabbit followed a circadian rhythm, heart rates being slower in the morning and faster in late afternoon and evening. The circadian rhythm was attenuated but not abolished by alinidine and nadolol. These results suggest that if prolongation of action potential duration by sustained beta blockade in patients after myocardial infarction contributes to protection against sudden death (by a class III antiarrhythmic action) then alinidine would not be expected to provide a comparable prophylaxis.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001919:Bradycardia / Q000503:physiopathology; D002940:Circadian Rhythm; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D009248:Nadolol / Q000494:pharmacology; D011817:Rabbits
chemical_list: D000319:Adrenergic beta-Antagonists; D009248:Nadolol; C022192:alinidine; D003000:Clonidine