Role of endogenous opioids in syncope induced by head-up tilt test and its relationship with isoproterenol-dependent and isoproterenol-independent neurally-mediated syncope

This study was designed to evaluate the role of endogenous opioids in neurally-mediated syncope. Head-up tilt test was performed on 35 patients with syncope of unknown origin. Plasma β-endorphin was measured (1) at baseline, (2) at the end of tilt test or at time of syncope, (3) 15 min before isoproterenol-test, (4) at the end of the isoproterenol-test or at time of syncope. Subjects with a positive tilt testing showed a larger rise in plasma β-endorphin concentrations at time of syncope (baseline 13.7±8.0 vs. syncope 41.4±26.4 pmol l−1; P<0.01). On the contrary, patients with a positive isoproterenol-test showed no rise in plasma β-endorphin levels (baseline 7.9±3.6 vs. syncope 7.4±2.7 pmol l−1; P=ns). Patients with a passive negative tilt test (baseline 6.7±2.8 vs. end of test 7.0±3.3 pmol l−1; P=ns) and negative isoproterenol tilt test (baseline 7.4±3.8 vs. end of test 8.1±3.4 pmol l−1; P=ns) showed no changes in β-endorphin concentrations. To further examine the efficacy of i.v. naloxone to prevent syncope, 10 patients were randomized to naloxone (0.02 mg/kg) or placebo. Second head-up tilt testing was negative in 1/5 patients with naloxone and in 2/5 patients with placebo. We conclude that, (1) endogenous opioids seem to be involved in vasovagal syncope induced by baseline head-up tilt test, (2) changes in plasma β-endorphin concentrations show significant differences between patients who have isoproterenol-dependent and isoproterenol-independent syncope, this finding might occur in the setting of different pathophysiologic mechanisms, and (3) intravenous naloxone at a dose of 0.02 mg/kg was not superior to placebo in order to prevent positive responses to baseline tilt test.