Endogenous opioids and epinephrine in nitroglycerin provocation tilt test in patients with neurally mediated syncope

Endogenous opioids and catecholamines are involved in autonomic activity. Nitroglycerin provocation tilt is a useful modality for evaluating neurally mediated syncope. Endogenous opioids and epinephrine might play an important role in nitroglycerin provocation tilt. To investigate whether or not opioids and catecholamines are involved in the pathogenesis of nitroglycerin provocation tilt, we measured the temporal changes of the plasma levels of beta endorphin, norepinephrine, and epinephrine in 64 patients with syncope of unknown etiology, and compared the findings with those of 16 patients who underwent isoproterenol provocation tilt (1-3 microg/min) test with a positive response. We performed a 20 minute control tilt (80 degrees) followed by a nitroglycerin provocation tilt of 20 minutes with the intravenous infusion of nitroglycerin. Nitroglycerin infusion was started at 250 microg/h, and was increased by 250 microg/h every 3 minutes up to 1500 microg/h during the tilt test. Beta-endorphin, norepinephrine, and epinephrine were measured in peripheral venous blood in the supine position 2, 10, and 20 minutes after the start of the tilt test, and also at the onset of syncope. Twenty-six patients had a positive response to the control tilt (group 1), and 22 patients had a positive response to nitroglycerin provocation tilt (group 2). The remaining 16 patients had a negative response to both control tilt and nitroglycerin provocation tilt (group 3), compared with isoproterenol provocation tilt patients (group 4). Beta-endorphin and epinephrine only significantly increased in groups 1 and 2 (beta-endorphin; from 7.3 +/- 3.3 pg/mL to 19.9 +/- 17.7 pg/mL, in group 1, P < 0.05; from 7.3 +/- 2.9 to 16.5 +/- 10.7 pg/mL, in group 2, P < 0.05; epinephrine; from 42 +/- 58 pg/mL to 157 +/- 161 pg/mL, in group 1, P < 0.05: from 33 +/- 25 to 202 +/- 252 pg/mL, in group 2, P < 0.05), but not in groups 3 and 4. Beta-endorphin and epinephrine might participate in the pathophysiology in conventional tilt-induced as well as nitroglycerin provocation tilt-induced syncope in patients with neurally mediated syncope.