REEXAMINATION OF THE ROLE OF ENDOGENOUS OPIATES IN SILENT-MYOCARDIAL-ISCHEMIA

Objectives. This study was designed to examine the role of beta- endor phin and met-enkephalin in the pathophysiology of silent myocardial is chemia, with emphasis on their role in the physiologic response to str ess. Background. Silent myocardial ischemia is more common in patients whose perception of pain is reduced. Whether endogenous opiates can c ontribute to this process remains uncertain largely because of the con flicting findings of previous studies. Methods. Forty-three patients w ith coronary artery disease and ischemia on treadmill stress testing u nderwent electrical pain tests and exercise treadmill tests during nal oxone and placebo infusion in a randomized, double-blind crossover stu dy. Thirty- one patients developed angina during both treadmill tests (group A), and 12 had silent ischemia (group B). Plasma beta-endorphin , met-enkephalin, epinephrine, norepinephrine and cortisol were measur ed before and after exercise in a subgroup of 17 patients. Results. Na loxone reduced electrical pain tolerance (1.40 +/- 0.10 [mean +/- SEM] vs. 1.72 +/- 0.19 mA, p = 0.04) but did not affect the time to angina in group A (260 +/- 20 vs. 248 +/- 20 s, p = 0.72) or induce angina i n group B patients. Beta-endorphin and met-enkephalin levels during pl acebo infusion were not significantly different in groups A and B at b aseline and after exercise, although beta-endorphin levels were signif icantly increased during naloxone infusion, confirming effective opiat e receptor blockade. Norepinephrine and cortisol increased with exerci se, but catecholamines and cortisol were similar in both groups and we re unaffected by naloxone. Conclusions. Beta-endorphin and met-enkepha lin were similar in patients with painful and silent ischemia, and nal oxone infusion did not influence anginal symptoms despite effective op iate receptor blockade and a reduction in somatic pain tolerance. Thes e findings suggest that endogenous opiates do not play an important ro le in modulating symptoms in myocardial ischemia. The increase in beta -endorphin with exercise that coincided with an increase in plasma cor tisol is most likely due to its release from the anterior pituitary gl and as part of the physiologic stress response.