title: Milrinone ameliorates cardiac mechanical dysfunction after hypothermia in an intact rat model.
abstract: BACKGROUND
  Rewarming from hypothermia is often complicated by cardiac dysfunction, characterized by substantial reduction in stroke volume. Previously we have reported that inotropic agents, working via cardiac β-receptor agonism may exert serious side effects when applied to treat cardiac contractile dysfunction during rewarming. In this study we tested whether Milrinone, a phosphodiesterase III inhibitor, is able to ameliorate such dysfunction when given during rewarming.
  
  
  METHODS
  A rat model designed for circulatory studies during experimental hypothermia with cooling to a core temperature of 15°C, stable hypothermia at this temperature for 3h and subsequent rewarming was used, with a total of 3 groups: (1) a normothermic group receiving Milrinone, (2) a hypothermic group receiving Milrinone the last hour of hypothermia and during rewarming, and (3) a hypothermic saline control group. Hemodynamic function was monitored using a conductance catheter introduced to the left ventricle.
  
  
  RESULTS
  After rewarming from 15°C, stroke volume and cardiac output returned to within baseline values in Milrinone treated animals, while these variables were significantly reduced in saline controls.
  
  
  CONCLUSIONS
  Milrinone ameliorated cardiac dysfunction during rewarming from 15°C. The present results suggest that at low core temperatures and during rewarming from such temperatures, pharmacologic efforts to support cardiovascular function is better achieved by substances preventing cyclic AMP breakdown rather than increasing its formation via β-receptor stimulation.
authors.affiliation: Department of Research and Education, Norwegian Air Ambulance Foundation, 1441 Drøbak, Norway; Anesthesia and Critical Care Research Group, Institute of Clinical Medicine, UiT, The Arctic University of Norway, 9037 Tromsø, Norway. Electronic address: erik.sveberg.dietrichs@norskluftambulanse.no.
authors.forename: Erik Sveberg
authors.initials: ES
authors.lastname: Dietrichs
authors.affiliation: Anesthesia and Critical Care Research Group, Institute of Clinical Medicine, UiT, The Arctic University of Norway, 9037 Tromsø, Norway. Electronic address: timofey.kondratiev@uit.no.
authors.forename: Timofei
authors.initials: T
authors.lastname: Kondratiev
authors.affiliation: Anesthesia and Critical Care Research Group, Institute of Clinical Medicine, UiT, The Arctic University of Norway, 9037 Tromsø, Norway; Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, 9019 Tromsø, Norway. Electronic address: torkjel.tveita@uit.no.
authors.forename: Torkjel
authors.initials: T
authors.lastname: Tveita
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007036:Hypothermia, Induced / Q000379:methods; D008297:Male; D020105:Milrinone / Q000627:therapeutic use*; D058987:Phosphodiesterase 3 Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017694:Rewarming / Q000009:adverse effects*; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D058987:Phosphodiesterase 3 Inhibitors; D020105:Milrinone
keywords: Accidental hypothermia; Cardiovascular support; Milrinone; PDE3 inhibitor; Rewarming; Rewarming shock; Therapeutic hypothermia