Reexamination of the role of endogenous opiates in silent myocardial ischemia.

OBJECTIVES

This study was designed to examine the role of beta-endorphin and met-enkephalin in the pathophysiology of silent myocardial ischemia, with emphasis on their role in the physiologic response to stress.

BACKGROUND

Silent myocardial ischemia is more common in patients whose perception of pain is reduced. Whether endogenous opiates can contribute to this process remains uncertain largely because of the conflicting findings of previous studies.

METHODS

Forty-three patients with coronary artery disease and ischemia on treadmill stress testing underwent electrical pain tests and exercise treadmill tests during naloxone and placebo infusion in a randomized, double-blind crossover study. Thirty-one patients developed angina during both treadmill tests (group A), and 12 had silent ischemia (group B). Plasma beta-endorphin, metenkephalin, epinephrine, norepinephrine and cortisol were measured before and after exercise in a subgroup of 17 patients.

RESULTS

Naloxone 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 in group B patients. Beta-endorphin and met-enkephalin levels during placebo infusion were not significantly different in groups A and B at baseline and after exercise, although beta-endorphin levels were significantly increased during naloxone infusion, confirming effective opiate receptor blockade. Norepinephrine and cortisol increased with exercise, but catecholamines and cortisol were similar in both groups and were unaffected by naloxone.

CONCLUSIONS

Beta-endorphin and met-enkephalin were similar in patients with painful and silent ischemia, and naloxone infusion did not influence anginal symptoms despite effective opiate receptor blockade and a reduction in somatic pain tolerance. These findings suggest that endogenous opiates do not play an important role in modulating symptoms in myocardial ischemia. The increase in beta-endorphin with exercise that coincided with an increase in plasma cortisol is most likely due to its release from the anterior pituitary gland as part of the physiologic stress response.