title: Dantrolene reduces the threshold and gain for shivering.
abstract: Dantrolene is used for treatment of life-threatening hyperthermia, yet its thermoregulatory effects are unknown. We tested the hypothesis that dantrolene reduces the threshold (triggering core temperature) and gain (incremental increase) of shivering. Healthy volunteers were evaluated on 2 random days: control and dantrolene (approximately 2.5 mg/kg plus a continuous infusion). In Study 1, 9 men were warmed until sweating was provoked and then cooled until arteriovenous shunt constriction and shivering occurred. Sweating was quantified on the chest using a ventilated capsule. Absolute right middle fingertip blood flow was quantified using venous-occlusion volume plethysmography. A sustained increase in oxygen consumption identified the shivering threshold. In Study 2, 9 men were given cold lactated Ringer's solution i.v. to reduce core temperature approximately 2 degrees C/h. Cooling was stopped when shivering intensity no longer increased with further core cooling. The gain of shivering was the slope of oxygen consumption versus core temperature regression. In Study 1, sweating and vasoconstriction thresholds were similar on both days. In contrast, shivering threshold decreased 0.3 +/- 0.3 degrees C, P = 0.004, on the dantrolene day. In Study 2, dantrolene decreased the shivering threshold from 36.7 +/- 0.2 to 36.3 +/- 0.3 degrees C, P = 0.01 and systemic gain from 353 +/- 144 to 211 +/- 93 mL.min(-1).degrees C(-1), P = 0.02. Thus, dantrolene substantially decreased the gain of shivering, but produced little central thermoregulatory inhibition.
  
  
  CONCLUSIONS
  Dantrolene substantially decreases the gain of shivering but produces relatively little central thermoregulatory inhibition. It thus seems unlikely to prove more effective than conventional muscle relaxants for treatment of life-threatening hyperthermia.
authors.affiliation: Outcomes Research Institute, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Lin
authors.forename: Sharma
authors.initials: S
authors.lastname: Neeru
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Doufas
authors.forename: Edwin
authors.initials: E
authors.lastname: Liem
authors.forename: Yunus
authors.initials: Y
authors.lastname: Muneer Shah
authors.forename: Anupama
authors.initials: A
authors.lastname: Wadhwa
authors.forename: Rainer
authors.initials: R
authors.lastname: Lenhardt
authors.forename: Andrew
authors.initials: A
authors.lastname: Bjorksten
authors.forename: Akiko
authors.initials: A
authors.lastname: Taguchi
authors.forename: Barhara
authors.initials: B
authors.lastname: Kabon
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
authors.forename: Andrea
authors.initials: A
authors.lastname: Kurz
mesh_terms: D000293:Adolescent; D000328:Adult; D001831:Body Temperature / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D003620:Dantrolene / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010108:Oxyhemoglobins / Q000378:metabolism; D012768:Shivering / Q000187:drug effects*; D012881:Skin Temperature / Q000187:drug effects / Q000502:physiology; D013546:Sweating / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D009125:Muscle Relaxants, Central; D010108:Oxyhemoglobins; D002245:Carbon Dioxide; D003620:Dantrolene