Marchant B, Umachandran V, Wilkinson P, Medbak S, Kopelman P G, Timmis A D
Department of Cardiology, London Chest Hospital, England, United Kingdom.
J Am Coll Cardiol. 1994 Mar 1;23(3):645-51. doi: 10.1016/0735-1097(94)90749-8.
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.
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.
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.
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.
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.
本研究旨在探讨β-内啡肽和甲硫氨酸脑啡肽在无症状性心肌缺血病理生理学中的作用，重点关注它们在应激生理反应中的作用。
在疼痛感知降低的患者中，无症状性心肌缺血更为常见。内源性阿片类物质是否参与这一过程仍不确定，这主要是因为先前研究结果相互矛盾。
在一项随机、双盲交叉研究中，43例经跑步机运动试验证实有冠状动脉疾病和缺血的患者，在输注纳洛酮和安慰剂期间接受电疼痛试验和运动跑步机试验。31例患者在两次跑步机试验中均出现心绞痛（A组），12例有无症状性缺血（B组）。在17例患者的亚组中，于运动前后测量血浆β-内啡肽、甲硫氨酸脑啡肽、肾上腺素、去甲肾上腺素和皮质醇。
纳洛酮降低了电疼痛耐受性（1.40±0.10[均值±标准误]对1.72±0.19 mA，p = 0.04），但不影响A组心绞痛发作时间（260±20对248±20 s，p = 0.72），也未在B组患者中诱发心绞痛。在基线和运动后，安慰剂输注期间A组和B组的β-内啡肽和甲硫氨酸脑啡肽水平无显著差异，尽管在纳洛酮输注期间β-内啡肽水平显著升高，证实了有效的阿片受体阻断。去甲肾上腺素和皮质醇随运动增加，但两组中的儿茶酚胺和皮质醇相似，且不受纳洛酮影响。
有疼痛性缺血和无症状性缺血的患者中β-内啡肽和甲硫氨酸脑啡肽相似，尽管阿片受体被有效阻断且躯体疼痛耐受性降低，但纳洛酮输注并未影响心绞痛症状。这些发现表明内源性阿片类物质在调节心肌缺血症状中不发挥重要作用。运动时β-内啡肽增加，同时血浆皮质醇增加，这很可能是由于其作为生理应激反应的一部分从前垂体释放。
