Adenosine-provoked angina pectoris-like pain--time characteristics, influence of autonomic blockade and naloxone

Abstract

In a study to characterize the time characteristics and the influence of blockade of beta, cholinergic and opioid receptors on the chest pain induced by adenosine, this agent was given as a bolus into a peripheral vein of six healthy volunteers (4 men) 24–45 years of age. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (1/3, 2/3, and a full maximum tolerable dose) and three doses of placebo were given as single blind doses in randomized order. Thereafter metoprolol (10 mg to males, 8 mg to females), followed by 1 mg atropine and then 0.4 mg naloxone were given intravenously. After each agent the test procedure was repeated. Heart rate and atrio-ventricular blocks were recorded by electrocardiography and respiration by dynamic spirometry. One minute after each dose of adenosine, the chest pain was scored. The maximum tolerable dose of adenosine was 80–15.9 mg. All subjects experienced angina pectoris-like pain. Following injection, onset of respiratory stimulation, AV-block and chest pain occurred after 14±4.0, 19±5.4 and 21±6.4 s, the differences being highly significant. Maximal respiratory stimulation occurred after 18±4.6, not statistically different from the onset of AV-block which in its turn occurred earlier (P<0.005) than the time for maximal central chest pain. 29±7.8 seconds. Metoprolol induced a 20% slowing of heart rate. After atropine there was a 30% faster heart rate. No significant differences were observed in respect of the onset and duration of AV-block and pain or degree of pain after the different interventions as compared to the control state. In conclusion, adenosine-induced angina pectoris-like pain occurs with a time profile different to that of respiratory stimulation and AV-block but with an onset very shortly after the AV-block. The three different interventions did not cause any change in the adendosine effects. The results suggest that the angina pectoris-like pain is provoked at myocardial adenosine receptors and that excitation and propagation of the nerve impulse is not affected by autonomic blockade or blockade of opioid receptors.