OBJECTIVES: Accidental hypothermia increases mortality and morbidity after hemorrhage, but controversial data are available on the effects of therapeutic hypothermia. Therefore, we tested the hypothesis whether moderate pretreatment hypothermia would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation. DESIGN: Prospective, controlled, randomized study. SETTING: University animal research laboratory. SUBJECTS: Twenty domestic pigs of either gender. INTERVENTIONS: Using an extracorporeal heat exchanger, anesthetized and instrumented animals were maintained at 38°C, 35°C, or 32°C core temperature and underwent 4 hours of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Resuscitation comprised of hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at preshock values. MEASUREMENTS AND MAIN RESULTS: Before, immediately at the end of, and 12 and 22 hours after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, and nitric oxide and cytokine production. Hemostasis was assessed by rotation thromboelastometry. Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and markers of apoptosis (kidney Bcl-xL and caspase-3 expression). Hypothermia at 32°C attenuated the shock-related lactic acidosis but caused metabolic acidosis, most likely resulting from reduced carbohydrate oxidation. Although hypothermia did not further aggravate shock-related coagulopathy, it caused a transitory attenuation of kidney and liver dysfunction, which was ultimately associated with reduced histological damage and more pronounced apoptosis. CONCLUSIONS: During long-term porcine hemorrhage and resuscitation, moderate pretreatment hypothermia was associated with a transitory attenuation of organ dysfunction and less severe histological tissue damage despite more pronounced metabolic acidosis. This effect is possibly due to a switch from necrotic to apoptotic cell death, ultimately resulting from reduced tissue energy deprivation during the shock phase.
OBJECTIVES: Accidental hypothermia increases mortality and morbidity after hemorrhage, but controversial data are available on the effects of therapeutic hypothermia. Therefore, we tested the hypothesis whether moderate pretreatment hypothermia would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation. DESIGN: Prospective, controlled, randomized study. SETTING: University animal research laboratory. SUBJECTS: Twenty domestic pigs of either gender. INTERVENTIONS: Using an extracorporeal heat exchanger, anesthetized and instrumented animals were maintained at 38°C, 35°C, or 32°C core temperature and underwent 4 hours of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Resuscitation comprised of hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at preshock values. MEASUREMENTS AND MAIN RESULTS: Before, immediately at the end of, and 12 and 22 hours after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, and nitric oxide and cytokine production. Hemostasis was assessed by rotation thromboelastometry. Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and markers of apoptosis (kidney Bcl-xL and caspase-3 expression). Hypothermia at 32°C attenuated the shock-related lactic acidosis but caused metabolic acidosis, most likely resulting from reduced carbohydrate oxidation. Although hypothermia did not further aggravate shock-related coagulopathy, it caused a transitory attenuation of kidney and liver dysfunction, which was ultimately associated with reduced histological damage and more pronounced apoptosis. CONCLUSIONS: During long-term porcine hemorrhage and resuscitation, moderate pretreatment hypothermia was associated with a transitory attenuation of organ dysfunction and less severe histological tissue damage despite more pronounced metabolic acidosis. This effect is possibly due to a switch from necrotic to apoptotic cell death, ultimately resulting from reduced tissue energy deprivation during the shock phase.
Authors: Oscar McCook; Peter Radermacher; Chiara Volani; Pierre Asfar; Anita Ignatius; Julia Kemmler; Peter Möller; Csaba Szabó; Matthew Whiteman; Mark E Wood; Rui Wang; Michael Georgieff; Ulrich Wachter Journal: Nitric Oxide Date: 2014-03-18 Impact factor: 4.427
Authors: Šárka Matějková; Angelika Scheuerle; Florian Wagner; Oscar McCook; José Matallo; Michael Gröger; Andrea Seifritz; Bettina Stahl; Brigitta Vcelar; Enrico Calzia; Michael Georgieff; Peter Möller; Hubert Schelzig; Peter Radermacher; Florian Simon Journal: Intensive Care Med Date: 2013-01-05 Impact factor: 17.440
Authors: Kai Oliver Jensen; Leonhard Held; Andrea Kraus; Frank Hildebrand; Philipp Mommsen; Ladislav Mica; Guido A Wanner; Peter Steiger; Rudolf M Moos; Hans-Peter Simmen; Kai Sprengel Journal: Eur J Med Res Date: 2016-10-06 Impact factor: 2.175
Authors: Frank Hildebrand; Peter Radermacher; Steffen Ruchholtz; Markus Huber-Lang; Andreas Seekamp; Sascha Flohé; Martijn van Griensven; Hagen Andruszkow; Hans-Christoph Pape Journal: Intensive Care Med Exp Date: 2014-05-15
Authors: Martin Wepler; Sebastian Hafner; Angelika Scheuerle; Matthias Reize; Michael Gröger; Florian Wagner; Florian Simon; José Matallo; Frank Gottschalch; Andrea Seifritz; Bettina Stahl; Martin Matejovic; Amar Kapoor; Peter Möller; Enrico Calzia; Michael Georgieff; Ulrich Wachter; Josef A Vogt; Christoph Thiemermann; Peter Radermacher; Oscar McCook Journal: Intensive Care Med Exp Date: 2013-10-29