title: Changes in cardiovascular effects of dopamine in response to graded hypothermia in vivo.
abstract: OBJECTIVE
  Inotropic drugs are frequently administered in hypothermic patients to support an assumed inadequate circulation, but their pharmacologic properties at reduced temperatures are largely unknown. Thus we estimated dopamine pharmacokinetics as well as left ventricular function and global hemodynamics after dopamine infusions at various core temperatures in a pig model of surface cooling and rewarming.
  
  
  METHODS
  Prospective, randomized, open, placebo-controlled experimental study.
  
  
  METHODS
  University-affiliated animal research laboratory.
  
  
  METHODS
  Sixteen healthy, anesthetized juvenile (2-3 months) castrated male pigs.
  
  
  METHODS
  After normothermic infusions of dopamine at different doses (4, 8, and 16 μg/kg/min), effects of dopamine (n = 8) or saline (n = 8) were tested at 25 °C and during rewarming (30-34 °C).
  
  
  RESULTS
  Dopamine half-time was 5.4 ± 0.7 min at normothermia, increased to 11.6 ± 0.8 min at 25 °C, but returned to control during rewarming at 34-35 °C. Dopamine infusion at 25 °C elevated dopamine plasma concentration four-fold compared to the same infusion rate at normothermia, leading to increased systemic vascular resistance index not seen at normothermia. Also, in contrast to the dopamine-mediated increase in cardiac index observed at normothermia, high-dose dopamine at 25 °C left cardiac index unchanged despite a concomitant increase in heart rate, since stroke index decreased by 43%. During rewarming, cardiovascular effects of dopamine at moderate hypothermia (30-34 °C) were principally similar to responses during normothermia.
  
  
  CONCLUSIONS
  Pharmacodynamic effects and pharmacokinetics of dopamine are maintained during the rewarming phase at moderate hypothermia. However, at 25 °C dopamine pharmacokinetics were seriously altered and dopamine failed to increase cardiac index since stroke index was reduced with incrementing dosages. Properties of the low-flow, high-viscosity circulatory state, combined with altered pharmacokinetics of dopamine, may explain lack of beneficial--and potentially harmful--effects from dopamine administration at 25 °C.
authors.affiliation: Departments of Anesthesiology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. ole.magnus.filseth@unn.no
authors.forename: Ole Magnus
authors.initials: OM
authors.lastname: Filseth
authors.forename: Ole-Jakob
authors.initials: OJ
authors.lastname: How
authors.forename: Timofei
authors.initials: T
authors.lastname: Kondratiev
authors.forename: Tor Magne
authors.initials: TM
authors.lastname: Gamst
authors.forename: Georg
authors.initials: G
authors.lastname: Sager
authors.forename: Torkjel
authors.initials: T
authors.lastname: Tveita
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects*; D002496:Central Venous Pressure / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007035:Hypothermia / Q000188:drug therapy / Q000503:physiopathology; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods; D008297:Male; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D004298:Dopamine