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 beta-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 beta-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 beta-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 beta-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 beta-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.
Pérez-Paredes
M
M
Cardiology Unit, University Hospital Morales Meseguer, Murcia, Spain. mpparedes@doymanet.es
Picó-Aracil
F
F
Fuentes-Jiménez
T
T
Sánchez-Villanueva
J G
JG
Expósito-Ordoñez
E
E
Gonzálvez-Ortega
M
M
González-Caballero
E
E
Nicolás-Garcia
F
F
Nuño de la Rosa
J A
JA
Ruiz-Ros
J A
JA
Ruipérez-Abizanda
J A
JA
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018847:Opioid Peptides / Q000502:physiology*; D019462:Syncope, Vasovagal / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D018667:Tilt-Table Test; D001615:beta-Endorphin / Q000097:blood / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D009270:Naloxone; D001615:beta-Endorphin; D007545:Isoproterenol