Tissue hemoglobin index: a non-invasive optical measure of total tissue hemoglobin

Introduction: The tissue hemoglobin index (THI) is a hemoglobin signal strength metric provided on the InSpectra ™ StO2 Tissue Oxygenation Monitor, Model 650. There is growing interest regarding the physiologic meaning of THI and whether a clinically useful correlation between THI and blood hemoglobin concentratio

Metabolic networks in a porcine model of trauma and hemorrhagic shock demonstrate different control mechanism with carbohydrate pre-feed

Background: Treatment with oral carbohydrate prior to trauma and hemorrhage confers a survival benefit in small animal models. The impact of fed states on survival in traumatically injured humans is unknown. This work uses regulatory networks to examine the effect of carbohydrate pre-feeding on metabolic response to polytrauma and hemorrhagic shock in a clinically-relevant large animal model. Methods: Male Yorkshire pigs were fasted overnight (n = 64). Pre-fed animals (n = 32) received an oral bolus of Karo\textregistered\syrup before sedation. All animals underwent a standardized trauma, hemorrhage, and resuscitation protocol. Serum samples were obtained at set timepoints. Proton NMR was used to identify and quantify serum metabolites. Metabolic regulatory networks were constructed from metabolite concentrations and rates of change in those concentrations to identify controlled nodes and controlling nodes of the network. Results: Oral carbohydrate pre-treatment was not associated with survival benefit. Six metabolites were identified as controlled nodes in both groups: adenosine, cytidine, glycerol, hypoxanthine, lactate, and uridine. Distinct groups of controlling nodes were associated with controlled nodes; however, the composition of these groups depended on feeding status. Conclusions: A common metabolic output, typically associated with injury and hypoxia, results from trauma and hemorrhagic shock. However, this output is directed by different metabolic inputs depending upon the feeding status of the subject. Nodes of the network that are related to mortality can potentially be manipulated for therapeutic effect; however, these nodes differ depending upon feeding status

d-β-Hydroxybutyrate and melatonin for treatment of porcine hemorrhagic shock and injury: a melatonin dose-ranging study

Abstract Objective Treatment with a combination of d-β-hydroxybutyrate (BHB) and melatonin (M) improves survival in hemorrhagic shock models. Our objective was to find the most effective melatonin concentration in combination with 4 molar BHB (4 M BHB). Survival and markers of organ injury were analyzed in pigs exposed to pulmonary contusion, liver crush injury, and hemorrhagic shock and treated with lactated Ringer’s solution; 4 M BHB/43 mM M; 4 M BHB/20 mM M; 4 M BHB/10 mM M; 4 M BHB/4.3 mM M; or 4 M BHB/0.43 mM M. This work is an extension of a previously published research study. Results Survival was highest in pigs receiving 4 M BHB/43 mM M (13/14), followed by lactated Ringer’s solution (11/16) and BHB/M with decreased melatonin concentrations (4 M BHB/20 mM M 3/6, 4 M BHB/10 mM M 2/6, 4 M BHB/4.3 mM M 3/6, 4 M BHB/0.43 mM M 1/6, p = 0.011). High mortality was associated with increases in serum lactate, higher liver and muscle injury markers and decreases in PaO2:FiO2 ratios. Our study indicates that treatment with 4 M BHB and melatonin concentrations below 43 mM lack the survival benefit observed from 4 M BHB/43 mM melatonin in pigs experiencing hemorrhagic shock and polytrauma

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Additional file 1. Average drug serum levels (a, b) and drug exposure over time (c, d) during hemorrhagic shock and injury

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Additional file 3. Urine 8-isoprostane levels during hemorrhagic shock and injury

A four-compartment metabolomics analysis of the liver, muscle, serum, and urine response to polytrauma with hemorrhagic shock following carbohydrate prefeed.

OBJECTIVE:Hemorrhagic shock accompanied by injury represents a major physiologic stress. Fasted animals are often used to study hemorrhagic shock (with injury). A fasted state is not guaranteed in the general human population. The objective of this study was to determine if fed animals would exhibit a different metabolic profile in response to hemorrhagic shock with trauma when compared to fasted animals. METHODS:Proton (1H) NMR spectroscopy was used to determine concentrations of metabolites from four different compartments (liver, muscle, serum, urine) taken at defined time points throughout shock/injury and resuscitation. PLS-DA was performed and VIP lists established for baseline, shock and resuscitation (10 metabolites for each compartment at each time interval) on metabolomics data from surviving animals. RESULTS:Fed status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The death rate for CPF animals is higher than FS animals (47 vs 28%). The majority of deaths occur post-resuscitation suggesting reperfusion injury. The metabolomics response to shock reflects priorities evident at baseline. FS animals raise the baseline degree of proteolysis to provide additional amino acids for energy production while CPF animals rely on both glucose and, to a lesser extent, amino acids. During early resuscitation levels of metabolites associated with energy production drop, suggesting diminished demand. CONCLUSIONS:Feeding status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The response to shock reflects metabolic priorities at baseline

Fed State Prior to Hemorrhagic Shock and Polytrauma in a Porcine Model Results in Altered Liver Transcriptomic Response

<div><p>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.</p></div