UNLABELLED: Profound hypothermic arrest ("suspended animation") is a new strategy to improve outcome following uncontrolled lethal hemorrhage (ULH). However, the impact of this approach on the immune/inflammatory response is unknown. This experiment was conducted to test the influence of profound hypothermia on markers of immune/inflammatory system. METHODS: ULH was induced in 32 female swine (80-120 lb) by creating an iliac artery and vein injury, followed 30 min later by laceration of the descending thoracic aorta. Through a left thoracotomy approach, total body hypothermic hyperkalemic metabolic arrest was induced by infusing organ preservation fluids into the aorta using a cardiopulmonary bypass machine (CPB). Experimental groups were (1) normothermic controls (no cooling, NC), or hypothermia induced at the following rates: (2) 0.5 degrees C/min (slow, SC), (3) 1 degrees C/min (medium, MC) and (4) 2 degrees C/min (fast, FC). Vascular injuries were repaired during 60 min of profound (10 degrees C) hypothermic arrest. Hyperkalemia was reversed by hypokalemic fluid exchange, and blood was infused for resuscitation during re-warming (0.5 degrees C/min). The surviving animals were monitored for 6 weeks. Levels of IL-1, TNFalpha, IL-6, IL-10, TGF-1 beta and heat shock protein (HSP-70) were measured by ELISA in serum samples collected serially during the experiment and post-operatively. RESULTS: Some of the immune markers were influenced by the use of CPB, independent of hypothermia (decrease in TGF-1 beta and increase in IL-1 beta). Hypothermia caused a significant decrease in IL-6, and an increase in HSP-70 expression compared to normothermic controls, independent of the cooling rate. An increase in IL-10 levels was noted which was influenced by the rate of cooling (p<0.05, MC versus NC). CONCLUSIONS: Profound hypothermia modulates the post-shock immune/inflammatory system by attenuating the pro-inflammatory IL-6, increasing anti-inflammatory IL-10 and augmenting the protective heat shock responses.
UNLABELLED: Profound hypothermic arrest ("suspended animation") is a new strategy to improve outcome following uncontrolled lethal hemorrhage (ULH). However, the impact of this approach on the immune/inflammatory response is unknown. This experiment was conducted to test the influence of profound hypothermia on markers of immune/inflammatory system. METHODS: ULH was induced in 32 female swine (80-120 lb) by creating an iliac artery and vein injury, followed 30 min later by laceration of the descending thoracic aorta. Through a left thoracotomy approach, total body hypothermic hyperkalemic metabolic arrest was induced by infusing organ preservation fluids into the aorta using a cardiopulmonary bypass machine (CPB). Experimental groups were (1) normothermic controls (no cooling, NC), or hypothermia induced at the following rates: (2) 0.5 degrees C/min (slow, SC), (3) 1 degrees C/min (medium, MC) and (4) 2 degrees C/min (fast, FC). Vascular injuries were repaired during 60 min of profound (10 degrees C) hypothermic arrest. Hyperkalemia was reversed by hypokalemic fluid exchange, and blood was infused for resuscitation during re-warming (0.5 degrees C/min). The surviving animals were monitored for 6 weeks. Levels of IL-1, TNFalpha, IL-6, IL-10, TGF-1 beta and heat shock protein (HSP-70) were measured by ELISA in serum samples collected serially during the experiment and post-operatively. RESULTS: Some of the immune markers were influenced by the use of CPB, independent of hypothermia (decrease in TGF-1 beta and increase in IL-1 beta). Hypothermia caused a significant decrease in IL-6, and an increase in HSP-70 expression compared to normothermic controls, independent of the cooling rate. An increase in IL-10 levels was noted which was influenced by the rate of cooling (p<0.05, MC versus NC). CONCLUSIONS: Profound hypothermia modulates the post-shock immune/inflammatory system by attenuating the pro-inflammatory IL-6, increasing anti-inflammatory IL-10 and augmenting the protective heat shock responses.
Authors: K Horst; F Hildebrand; R Pfeifer; S Hübenthal; K Almahmoud; M Sassen; T Steinfeldt; H Wulf; S Ruchholtz; H C Pape; D Eschbach Journal: Eur J Trauma Emerg Surg Date: 2015-02-28 Impact factor: 3.693
Authors: Rithwik Ramachandran; Eric Hyun; Liena Zhao; Tamia K Lapointe; Kevin Chapman; Christina L Hirota; Subrata Ghosh; David D McKemy; Nathalie Vergnolle; Paul L Beck; Christophe Altier; Morley D Hollenberg Journal: Proc Natl Acad Sci U S A Date: 2013-04-17 Impact factor: 11.205
Authors: Michael Frink; Sascha Flohé; Martijn van Griensven; Philipp Mommsen; Frank Hildebrand Journal: Mediators Inflamm Date: 2012-03-13 Impact factor: 4.711
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