Adenosine causes bradycardia in pacing-induced cardiac failure.
BACKGROUND
In normal, conscious dogs, systemic injection of adenosine causes arterial hypotension and a baroreceptor reflex tachycardia mediated in part by withdrawal of vagal tone from the sinoatrial node. After vagal section or muscarinic receptor blockade, however, adenosine injection causes bradycardia via a direct sinoatrial node inhibition. Because cardiac failure is marked by a loss of vagal tone, we hypothesized that adenosine injection in dogs with failing hearts would reduce heart rate.


RESULTS
Mongrel dogs were instrumented with indwelling catheters, manometers, and ventricular pacing electrodes. After the dogs had recovered from the surgery, the ventricles were paced continuously at 210 beats per minute for 3 weeks, followed by pacing at 240 beats per minute for an additional week. This regimen caused mild ventricular and more striking atrial hypertrophy and a gradual onset of physiological and clinical signs of congestive heart failure. Adenosine injections that caused large tachycardias before the pacing regimen began caused progressively smaller increments in heart rate during the first 2 weeks of pacing. After 3 and 4 weeks, adenosine injections caused overt reductions in heart rate despite the concomitant arterial depressor response.


CONCLUSIONS
We conclude that the loss of vagal tone associated with the development of cardiac failure unmasks the direct negative chronotropic effect of exogenous adenosine on the sinoatrial node.
Belloni
F L
FL
Department of Physiology, New York Medical College, Valhalla 10595.
Wang
J
J
Hintze
T H
TH
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002304:Cardiac Pacing, Artificial; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D003864:Depression, Chemical; D004285:Dogs; D006321:Heart / Q000294:innervation; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000503:physiopathology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D012849:Sinoatrial Node / Q000187:drug effects*
D000241:Adenosine