The relationship between plasma beta-endorphin, opioid receptor activity, and silent myocardial ischemia

Objective To investigate the role of the opioid system in the pathophysiology of silent ischemia through opiate antagonism with naloxone, and to determine the reproducibility of resting and postexercise beta-endorphin levels in predominantly asymptomatic patients with coronary artery disease. Design Randomized, double-blind, placebo-controlled crossover trial. Setting A University hospital referral center. Patients Ten patients with prior evidence of silent exercise-induced ischemia were studied. Intervention An infusion of saline placebo or naloxone at two dose regimens of 0.015 mg/kg or 0.15 mg/kg before supine exercise testing during three separate occasions for each patient. Outcome measures Plasma beta-endorphin was measured at rest, immediately after exercise, and 5 min poststress. Timing and severity of angina and exercise hemodynamics were also determined. Results Seven of 10 patients reported no angina, whereas the other three experienced angina with placebo and after administration of naloxone at both doses. The severity and duration of angina was consistently noted to decrease in these patients after naloxone administration, especially after low-dose naloxone relative to placebo. There were no apparent correlations between beta-endorphin levels and the characteristics of angina in these three patients, nor between beta-endorphin and hemodynamic responses in all patients in the study. Conclusions (a) naloxone failed to precipitate angina in this population of patients with silent ischemia; (b) naloxone appears to exert an analgesic effect at low doses; and (c) a variability of 5 pM at rest and 13 pM after exercise might be expected in predominantly asymptomatic patients due to random variation, which is comparable with results found in normal subjects.