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Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.

Determan C, Anderson R, Becker A, Witowski N, Lusczek E, Mulier K, Beilman GJ - PLoS ONE (2014)

Bottom Line: Resuscitation often results in reperfusion injury and survivors are susceptible to developing multiple organ failure (MOF).Our findings also suggest that the fasting state, relative to a carbohydrate prefed state, displays decreased carbohydrate metabolism, increased cytoskeleton reorganization and decreased inflammation in response to hemorrhagic shock and reperfusion.Evidence suggests that this is a consequence of a shrunken, catabolic state of the liver cells which provides an anti-inflammatory condition that partially mitigates hepatocellar damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.

ABSTRACT
Hemorrhagic shock is a leading cause of trauma-related mortality in both civilian and military settings. Resuscitation often results in reperfusion injury and survivors are susceptible to developing multiple organ failure (MOF). The impact of fed state on the overall response to shock and resuscitation has been explored in some murine models but few clinically relevant large animal models. We have previously used metabolomics to establish that the fed state results in a different metabolic response in the porcine liver following hemorrhagic shock and resuscitation. In this study, we used our clinically relevant model of hemorrhagic shock and polytrauma and the Illumina HiSeq platform to determine if the liver transcriptomic response is also altered with respect to fed state. Functional analysis of the response to shock and resuscitation confirmed several typical responses including carbohydrate metabolism, cytokine inflammation, decreased cholesterol synthesis, and apoptosis. Our findings also suggest that the fasting state, relative to a carbohydrate prefed state, displays decreased carbohydrate metabolism, increased cytoskeleton reorganization and decreased inflammation in response to hemorrhagic shock and reperfusion. Evidence suggests that this is a consequence of a shrunken, catabolic state of the liver cells which provides an anti-inflammatory condition that partially mitigates hepatocellar damage.

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Mentions: Sixty four (64) juvenile, male Yorkshire pigs were used in this study. All animals were fasted overnight. Two experimental groups were utilized: Carbohydrate Prefed (CPF, n = 32) and Fasted (FS, n = 32). CPF animals were given 7cc/kg bolus of Karo Syrup (mixture of sugars including ∼ 15% glucose, maltose, fructose and sucrose) diluted with water 1 hour prior to induction. The full experimental polytrauma and shock protocols have been described in detail previously [9], [10]. Briefly, animals were instrumented and splenectomized. Polytrauma was induced by a captive bolt device to create a blunt percussive injury to the chest followed by hemorrhage and a liver crush injury using a Holcomb clamp technique [11]. Hemorrhagic shock was induced by withdrawal of blood from the inferior vena cava until a systolic pressure of 45 to 55 mmHg was reached for 45 minutes (S45) to simulate time prior to medical help. Typically, this resulted in withdrawal of approximately 40% of the pig’s blood volume. Blood was placed in an acid-citrate-dextrose bag for later use. Following the shock period, animals received lactated Ringer’s fluid given as 20 cc/kg intravenous (IV) boluses to maintain a systolic blood pressure greater than 80 mmHg for one hour of limited resuscitation to simulate transportation to a medical center; then underwent full resuscitation protocol for the following 24 hours (Figure 1). This resuscitation included fluid, shed blood, and ventilator support per our standard protocol. After the resuscitation period, animals were extubated and sent to recovery and subsequently euthanized.


Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.

Determan C, Anderson R, Becker A, Witowski N, Lusczek E, Mulier K, Beilman GJ - PLoS ONE (2014)

Graphical representation of the experimental timeline described in Methods.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061062&req=5

pone-0100088-g001: Graphical representation of the experimental timeline described in Methods.
Mentions: Sixty four (64) juvenile, male Yorkshire pigs were used in this study. All animals were fasted overnight. Two experimental groups were utilized: Carbohydrate Prefed (CPF, n = 32) and Fasted (FS, n = 32). CPF animals were given 7cc/kg bolus of Karo Syrup (mixture of sugars including ∼ 15% glucose, maltose, fructose and sucrose) diluted with water 1 hour prior to induction. The full experimental polytrauma and shock protocols have been described in detail previously [9], [10]. Briefly, animals were instrumented and splenectomized. Polytrauma was induced by a captive bolt device to create a blunt percussive injury to the chest followed by hemorrhage and a liver crush injury using a Holcomb clamp technique [11]. Hemorrhagic shock was induced by withdrawal of blood from the inferior vena cava until a systolic pressure of 45 to 55 mmHg was reached for 45 minutes (S45) to simulate time prior to medical help. Typically, this resulted in withdrawal of approximately 40% of the pig’s blood volume. Blood was placed in an acid-citrate-dextrose bag for later use. Following the shock period, animals received lactated Ringer’s fluid given as 20 cc/kg intravenous (IV) boluses to maintain a systolic blood pressure greater than 80 mmHg for one hour of limited resuscitation to simulate transportation to a medical center; then underwent full resuscitation protocol for the following 24 hours (Figure 1). This resuscitation included fluid, shed blood, and ventilator support per our standard protocol. After the resuscitation period, animals were extubated and sent to recovery and subsequently euthanized.

Bottom Line: Resuscitation often results in reperfusion injury and survivors are susceptible to developing multiple organ failure (MOF).Our findings also suggest that the fasting state, relative to a carbohydrate prefed state, displays decreased carbohydrate metabolism, increased cytoskeleton reorganization and decreased inflammation in response to hemorrhagic shock and reperfusion.Evidence suggests that this is a consequence of a shrunken, catabolic state of the liver cells which provides an anti-inflammatory condition that partially mitigates hepatocellar damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Critical Care and Acute Care Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.

ABSTRACT
Hemorrhagic shock is a leading cause of trauma-related mortality in both civilian and military settings. Resuscitation often results in reperfusion injury and survivors are susceptible to developing multiple organ failure (MOF). The impact of fed state on the overall response to shock and resuscitation has been explored in some murine models but few clinically relevant large animal models. We have previously used metabolomics to establish that the fed state results in a different metabolic response in the porcine liver following hemorrhagic shock and resuscitation. In this study, we used our clinically relevant model of hemorrhagic shock and polytrauma and the Illumina HiSeq platform to determine if the liver transcriptomic response is also altered with respect to fed state. Functional analysis of the response to shock and resuscitation confirmed several typical responses including carbohydrate metabolism, cytokine inflammation, decreased cholesterol synthesis, and apoptosis. Our findings also suggest that the fasting state, relative to a carbohydrate prefed state, displays decreased carbohydrate metabolism, increased cytoskeleton reorganization and decreased inflammation in response to hemorrhagic shock and reperfusion. Evidence suggests that this is a consequence of a shrunken, catabolic state of the liver cells which provides an anti-inflammatory condition that partially mitigates hepatocellar damage.

Show MeSH
Related in: MedlinePlus