title: Presyncope during progressive hypovolaemia simulated by lower body negative pressure is not prevented by high-dose naloxone.
abstract: BACKGROUND
  The haemodynamic response to progressive hypovolaemia, whether simulated by lower body negative pressure (LBNP) or head-up tilt, or induced by haemorrhage or haemodialysis, has a typical biphasic pattern: a first, sympathoexcitatory, phase of vasoconstriction, tachycardia, and stable blood pressure, and a second, sympathoinhibitory, phase of vasodilatation, bradycardia, and hypotension. The opioid system is involved in this response, since animal studies showed that opioid antagonism by naloxone can attenuate hypovolaemic hypotension. In humans, this finding could not be confirmed. We hypothesized that this could result from inadequate dosing.
  
  
  METHODS
  Six healthy subjects underwent LBNP at -45 mmHg until presyncope before and after administration of naloxone 2 mg/kg. During the study, blood pressure, heart rate, vascular resistance, cardiac output, and plasma beta-endorphin were measured.
  
  
  RESULTS
  LBNP caused an immediate increase in vasoconstriction and heart rate, resulting in stable blood pressure. After 12 +/- 3.5 min, vasodilatory hypotension followed, accompanied by a modest increase in plasma beta-endorphin. Naloxone did not alter the first or the second phase of the circulatory response, and tolerance to LBNP even tended to decrease (hypotension after 7.5 +/- 2.0 min, NS). Pre-LBNP plasma beta-endorphin as well as hypotensive levels were increased after naloxone.
  
  
  CONCLUSIONS
  Our results suggest that naloxone, in a sufficient dose to interfere with the opioid system, does not influence the circulatory response to simulated hypovolaemia in humans is not influenced by naloxone. Given the mechanistic resemblance of LBNP hypotension to dialysis-induced hypotension, we propose that high-dose naloxone is not useful to treat the latter form of hypotension.
authors.affiliation: Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Ligtenberg
authors.forename: P J
authors.initials: PJ
authors.lastname: Blankestijn
authors.forename: H A
authors.initials: HA
authors.lastname: Koomans
mesh_terms: D000328:Adult; D001810:Blood Volume / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008150:Lower Body Negative Pressure; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009433:Neural Inhibition / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013575:Syncope / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone