Mild hypothermia attenuates circulatory and pulmonary dysfunction during experimental endotoxemia

TY - JOUR

T1 - Mild hypothermia attenuates circulatory and pulmonary dysfunction during experimental endotoxemia

AU - Schwarzl, Michael

AU - Seiler, Sebastian

AU - Wallner, Markus

AU - von Lewinski, Dirk

AU - Huber, Stefan

AU - Maechler, Heinrich

AU - Steendijk, Paul

AU - Zelzer, Sieglinde

AU - Truschnig-Wilders, Martie

AU - Obermayer-Pietsch, Barbara

AU - Lueger, Andreas

AU - Pieske, Burkert M

AU - Post, Heiner

PY - 2013/12

Y1 - 2013/12

N2 - OBJECTIVE: We tested whether mild hypothermia impacts on circulatory and respiratory dysfunction during experimental endotoxemia.DESIGN: Randomized controlled prospective experimental study.SETTING: Large animal facility, Medical University of Graz, Austria.SUBJECTS: Thirteen anesthetized and mechanically ventilated pigs.INTERVENTIONS: 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.MEASUREMENTS AND MAIN 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.CONCLUSION: 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.

AB - OBJECTIVE: We tested whether mild hypothermia impacts on circulatory and respiratory dysfunction during experimental endotoxemia.DESIGN: Randomized controlled prospective experimental study.SETTING: Large animal facility, Medical University of Graz, Austria.SUBJECTS: Thirteen anesthetized and mechanically ventilated pigs.INTERVENTIONS: 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.MEASUREMENTS AND MAIN 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.CONCLUSION: 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.

KW - Animals

KW - Cardiac Output

KW - Cardiotonic Agents/pharmacology

KW - Cytokines/blood

KW - Endotoxemia/blood

KW - Heart Rate

KW - Heart Ventricles/physiopathology

KW - Hypothermia, Induced

KW - Isoproterenol/pharmacology

KW - Lipopolysaccharides

KW - Myocardial Contraction/drug effects

KW - Norepinephrine/blood

KW - Oxygen/blood

KW - Random Allocation

KW - Swine

KW - Vascular Resistance

U2 - 10.1097/CCM.0b013e31829791da

DO - 10.1097/CCM.0b013e31829791da

M3 - SCORING: Journal article

C2 - 23963130

VL - 41

SP - e401-10

JO - CRIT CARE MED

JF - CRIT CARE MED

SN - 0090-3493

IS - 12

ER -