title: Inotropic Effects of Experimental Hyperthermia and Hypothermia on Left Ventricular Function in Pigs-Comparison With Dobutamine.
abstract: OBJECTIVE
  The results from the recent Targeted Temperature Management trial raised the question whether cooling or merely the avoidance of fever mediates better neurologic outcome in resuscitated patients. As temperature per se is a major determinant of cardiac function, we characterized the effects of hyperthermia (40.5°C), normothermia (38.0°C), and mild hypothermia (33.0°C) on left ventricular contractile function in healthy pigs and compared them with dobutamine infusion.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  Large animal facility, Medical University of Graz, Graz, Austria.
  
  
  METHODS
  Nine anesthetized and mechanically ventilated closed-chest Landrace pigs (67 ± 2 kg).
  
  
  METHODS
  Core body temperature was controlled using an intravascular device. At each temperature step, IV dobutamine was titrated to double maximum left ventricular dP/dt (1.8 ± 0.1 µg/kg/min at normothermia). Left ventricular pressure-volume relationships were assessed during short aortic occlusions. Left ventricular contractility was assessed by the calculated left ventricular end-systolic volume at an end-systolic left ventricular pressure of 100 mm Hg.
  
  
  RESULTS
  Heart rate (98 ± 4 vs 89 ± 4 vs 65 ± 2 beats/min; all p < 0.05) and cardiac output (6.7 ± 0.3 vs 6.1 ± 0.3 vs 4.4 ± 0.2 L/min) decreased with cooling from hyperthermia to normothermia and mild hypothermia, whereas left ventricular contractility increased (left ventricular end-systolic volume at a pressure of 100 mm Hg: 74 ± 5 mL at hyperthermia, 52 ± 4 mL at normothermia, and 41 ± 3 mL at mild hypothermia; all p < 0.05). The effect of cooling on left ventricular end-systolic volume at a pressure of 100 mm Hg (hyperthermia to normothermia: -28% ± 3% and normothermia to mild hypothermia: -20% ± 5%) was of comparable effect size as dobutamine at a given temperature (hyperthermia: -28% ± 4%, normothermia: -27% ± 6%, and mild hypothermia: -27% ± 9%).
  
  
  CONCLUSIONS
  Cooling from hyperthermia to normothermia and from normothermia to mild hypothermia increased left ventricular contractility to a similar degree as a significant dose of dobutamine in the normal porcine heart. These data indicate that cooling can reduce the need for positive inotropes and that lower rather than higher temperatures are appropriate for the resuscitated failing heart.
authors.affiliation: 1Department of Cardiology, Medical University of Graz, Graz, Austria.2Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany.3Department of Cardiothoracic Surgery, Medical University of Graz, Graz, Austria.4Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.5Department of Cardiology, Charité Berlin Campus Virchow, Berlin, Germany.
authors.forename: Alessio
authors.initials: A
authors.lastname: Alogna
authors.forename: Martin
authors.initials: M
authors.lastname: Manninger
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarzl
authors.forename: Birgit
authors.initials: B
authors.lastname: Zirngast
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Jochen
authors.initials: J
authors.lastname: Verderber
authors.forename: David
authors.initials: D
authors.lastname: Zweiker
authors.forename: Heinrich
authors.initials: H
authors.lastname: Maechler
authors.forename: Burkert M
authors.initials: BM
authors.lastname: Pieske
authors.forename: Heiner
authors.initials: H
authors.lastname: Post
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D002302:Cardiac Output; D004280:Dobutamine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006979:Hyperthermia, Induced / Q000379:methods; D007036:Hypothermia, Induced / Q000379:methods; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D013318:Stroke Volume; D034421:Sus scrofa; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
chemical_list: D004280:Dobutamine