Arrhythmogenic effects of catecholamines are decreased in heart failure induced by rapid pacing in dogs.
Increased circulating catecholamines are considered to be arrhythmogenic in heart failure. It is unclear whether increased circulating catecholamines contribute directly to ventricular arrhythmias or are only markers of the severity of heart failure. The present study determined the sensitivity of the failing heart to the arrhythmogenic effect of exogenous norepinephrine in a rapid pacing-induced model of heart failure in dogs (240 beats for 4 wk, n = 14). A similarly operated, non-paced group served as controls (n = 9). Cardiac sensitivity to the arrhythmogenic effect of catecholamines was determined by measuring the minimal dose of exogenous norepinephrine that induced ventricular tachycardia (arrhythmogenic threshold dose, ATD). ATD significantly increased after development of heart failure in heart-failure group (1.62 +/- 0.32 microgram/kg at baseline vs. 16.65 +/- 3.48 micrograms/kg at restudy, P < 0.01), whereas no significant change was noted in the control group (1.08 +/- 0.36 microgram/kg at baseline vs. 2.53 +/- 0.36 micrograms/kg at restudy, P > 0.10). Action potential duration was unchanged by superfusion with 10(-7) M isoproterenol in both ventricular muscles (230.2 +/- 6.1 vs. 229.7 +/- 5.3 ms, P = NS) and Purkinje fibers (273.2 +/- 6.5 vs. 283.8 +/- 4.2 ms, P = NS) from the failing hearts, although isoproterenol induced a shortening in the control group (204.8 +/- 0.9 vs. 181.3 +/- 1.6 ms in ventricular muscles, P < 0.01; 313.8 +/- 6.5 vs. 279.5 +/- 5.7 ms in Purkinje fibers, P < 0.01). We conclude that the failing heart has a decreased sensitivity to the arrhythmogenic effect of catecholamines.
Li
H G
HG
Department of Physiology, University of Western Ontario, London, Canada.
Jones
D L
DL
Yee
R
R
Klein
G J
GJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D013997:Time Factors
D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine