title: Mild hypothermia attenuates circulatory and pulmonary dysfunction during experimental endotoxemia.
abstract: OBJECTIVE
  We tested whether mild hypothermia impacts on circulatory and respiratory dysfunction during experimental endotoxemia.
  
  
  METHODS
  Randomized controlled prospective experimental study.
  
  
  METHODS
  Large animal facility, Medical University of Graz, Austria.
  
  
  METHODS
  Thirteen anesthetized and mechanically ventilated pigs.
  
  
  METHODS
  Lipopolysaccharide was administered for 4 hours. With the beginning of lipopolysaccharide infusion, animals were assigned to either normothermia (38°C, n = 7) or mild hypothermia (33°C, n = 6, intravascular cooling) and followed for 8 hours in total.
  
  
  RESULTS
  At the end of the protocol, cardiac output was lower in mild hypothermia than in normothermia (4.5 ± 0.4 L/min vs 6.6 ± 0.4 L/min, p < 0.05), but systemic vascular resistance (885 ± 77 dyn·s/cm vs 531 ± 29 dyn·s/cm, p < 0.05) and (Equation is included in full-text article.)(77% ± 6% vs 54% ± 3%, p < 0.05) were higher. Indices of left ventricular contractility in vivo were not different between groups. The high-frequency band in spectral analysis of heart rate variability indicated a better preserved vagal autonomic modulation of sinuatrial node activity in mild hypothermia versus normothermia (87 ± 5 vs 47 ± 5, normalized units, p < 0.05). Plasma norepinephrine levels were elevated compared with baseline in normothermia (2.13 ± 0.27 log pg/mL vs 0.27 ± 0.17 log pg/mL, p < 0.05) but not in mild hypothermia (1.02 ± 0.31 vs 0.55 ± 0.26, p = not significant). At 38°C in vitro, left ventricular muscle strips isolated from the mild hypothermia group had a higher force response to isoproterenol. SaO2 (100% ± 0% vs 92% ± 3%, p < 0.05) and the oxygenation index (PO2/FIO2, 386 ± 52 mm Hg vs 132 ± 32 mm Hg, p < 0.05) were substantially higher in mild hypothermia versus normothermia. Plasma cytokine levels were not consistently different between groups (interleukin 10) or higher (tumor necrosis factor-α and interleukin 6 and 8) during mild hypothermia versus normothermia.
  
  
  CONCLUSIONS
  The induction of mild hypothermia attenuates cardiac and respiratory dysfunction and counteracts sympathetic activation during experimental endotoxemia. This was not associated with lower plasma cytokine levels, indicating a reduction of cytokine responsiveness by mild hypothermia.
authors: 1Department of Cardiology, Medical University of Graz, Graz, Austria. 2Department of Cardiothoracic Surgery, Medical University of Graz, Graz, Austria. 3Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 4Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 5Department of Endocrinology and Nuclear Medicine, Medical University of Graz, Graz, Austria. 6Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Michael
authors: M
authors: Schwarzl
authors: Sebastian
authors: S
authors: Seiler
authors: Markus
authors: M
authors: Wallner
authors: Dirk
authors: D
authors: von Lewinski
authors: Stefan
authors: S
authors: Huber
authors: Heinrich
authors: H
authors: Maechler
authors: Paul
authors: P
authors: Steendijk
authors: Sieglinde
authors: S
authors: Zelzer
authors: Martie
authors: M
authors: Truschnig-Wilders
authors: Barbara
authors: B
authors: Obermayer-Pietsch
authors: Andreas
authors: A
authors: Lueger
authors: Burkert M
authors: BM
authors: Pieske
authors: Heiner
authors: H
authors: Post
mesh_terms: D000818:Animals; D002302:Cardiac Output; D002316:Cardiotonic Agents / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy*; D006339:Heart Rate; D006352:Heart Ventricles / Q000503:physiopathology; D007036:Hypothermia, Induced; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000097:blood; D011897:Random Allocation; D013552:Swine; D014655:Vascular Resistance
chemical_list: D002316:Cardiotonic Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D007545:Isoproterenol; D010100:Oxygen; D009638:Norepinephrine