Cardiac and respiratory effects of adenosine in man
Adenosine is a nucleoside with varied pharmacological effects but its actions in man are sparsely documented. Cardiac and respiratory effects of adenosine in man were examined. Adenosine was found to increase coronary flow in patients without significant coronary atheroma. Adenosine restored sinus rhythm in some patients with supraventricular tachycardia. In those in whom sinus rhythm was not restored the underlying rhythm was atrial flutter. In patients with complete heart block adenosine decreased ventricular rate in a dose-related fashion. In subjects in sinus rhythm adenosine produced a transient dose-related bradycardia which was followed by a more sustained increase in sinus rate. These latter effects were compared but were found not to differ in young and elderly subjects. A dose-related respiratory stimulant effect of adenosine, which had not previously been widely appreciated, was observed. The possible relevance of this observation to the ventilatory response to hypoxia is discussed. Adenosine-induced respiratory stimulation was found not to differ in young and elderly subjects. Dipyridamole, an inhibitor of adenosine transport, potentiated adenosine-induced respiratory stimulation and bradycardia but not the subsequent tachycardia. Aminophylline, a competitive adenosine antagonist at cell-surface receptors, abolished adenosine-induced bradycardia but did not alter the tachycardia or respiratory stimulation. Adenosine-induced bradycardia in man may be explained by an action of adenosine on cell-surface receptors at one site, whereas such an explanation does not accord with the observations on tachycardia and respiratory stimulation. Adenosine administered proximal to the carotid circulation in man stimulated respiration, but infusion distal to those vessels had no such effect. These observations are consistent with the hypothesis that adenosine stimulates respiration in man by an action on the carotid body. Possible physiological, pathophysiological and therapeutic implications of these observations are discussed.