Perioperative Coagulation Changes in Total Pancreatectomy and Islet Autotransplantation.

Objectives: Thrombotic complications after total pancreatectomy with islet autotransplantation (TPIAT) are common. However, the systemic changes to coagulation in the perioperative period have not been well studied. Our objective was to evaluate the derangements in coagulation in the perioperative period for this procedure.

Alterations in Enteroendocrine Hormones After Total Pancreatectomy With Islet Autotransplantation.

Objective: When total pancreatectomy with islet autotransplantation (TPIAT) is performed for chronic pancreatitis, the pancreas and most of the duodenum are removed, with Roux-en-Y reconstruction of the gastrointestinal tract. Enteroendocrine cells in the intestines and pancreas secrete hormones coordinating digestion and motility, but anatomic reconstruction alters transit of nutrients to these cells. We hypothesized that TPIAT leads to changes in enteroendocrine hormones.

Evaluation of novel formulations of d-β-hydroxybutyrate and melatonin in a rat model of hemorrhagic shock.

d-β-hydroxybutyrate and melatonin (BHB/MLT) infusion improves survival in hemorrhagic shock models. The original BHB/MLT formulation contains dimethyl sulfoxide (DMSO) to increase melatonin solubility. We formulated BHB/MLT solutions wherein DMSO was replaced either with 10% polyvinylpyrrolidone (BHB/MLT/PVP) or with 5% hydroxypropyl-β-cyclodextrin/2.

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

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.

Metabolomic analysis of survival in carbohydrate pre-fed pigs subjected to shock and polytrauma.

Hemorrhagic shock, a result of extensive blood loss, is a dominant factor in battlefield morbidity and mortality. Early rodent studies in hemorrhagic shock reported carbohydrate feeding prior to the induction of hemorrhagic shock decreased mortality. When repeated in our laboratory with a porcine model, carbohydrate pre-feed resulted in a 60% increase in death rate following hemorrhagic shock with trauma when compared to fasted animals (15/32 or 47% vs.

Safety of D-ß-Hydroxybutyrate and Melatonin for the Treatment of Hemorrhagic Shock With Polytrauma.

D-ß-hydroxybutyrate (BHB) and melatonin (M) treatment improves survival in animal models of hemorrhagic shock. Here, we evaluated the safety of BHB/M via 2 routes of administration in a porcine hemorrhagic shock/polytrauma model. Furthermore, we assessed BHB/M serum concentrations after intravenous and intraosseous infusion of different BHB/M doses in healthy pigs.

Preinjury Fed State Alters the Physiologic Response in a Porcine Model of Hemorrhagic Shock and Polytrauma.

Introduction: Hemorrhagic shock and injury lead to dramatic changes in metabolic demands and continue to be a leading cause of death. We hypothesized that altering the preinjury metabolic state with a carbohydrate load prior to injury would affect subsequent metabolic responses to injury and lead to improved survival.

Methods: Sixty-four pigs were randomized to fasted (F) or carbohydrate prefeeding (CPF) groups and fasted 12 h prior to experiment.

Bovine serum albumin as a molecular sensor for the discrimination of complex metabolite samples.

The potential for using serum albumin (SA) as a broadly applicable molecular sensor was explored in an effort to develop a method for rapid analysis of complex metabolite samples. SA is a protein present at high concentration in blood, which transports a diverse set of compounds including fatty acids, hormones, and drugs. The effectiveness of the bovine ortholog (BSA) as a molecular sensor was tested by analyzing the pool of small molecules bound to the protein after a brief incubation with complex fluids of biological origin.

Low StO2 measurements in surgical intensive care unit patients is associated with poor outcomes.

Background: Near-infrared spectroscopy-derived tissue hemoglobin saturation (StO2) is a noninvasive measurement that reflects changes in microcirculatory tissue perfusion. Previous studies in trauma patients have shown a correlation between low StO2 levels and mortality, organ failure, and severity of injury. The goals of this study were to identify the incidence of low StO2 in the critically ill patient population of a surgical intensive care unit (SICU) and evaluate the relationship of low StO2 and clinical outcomes.

Prolonged induced hypothermia in hemorrhagic shock is associated with decreased muscle metabolism: a nuclear magnetic resonance-based metabolomics study.

Hemorrhagic shock is a leading cause of trauma-related death in war and is associated with significant alterations in metabolism. Using archived serum samples from a previous study, the purpose of this work was to identify metabolic changes associated with induced hypothermia in a porcine model of hemorrhagic shock. Twelve Yorkshire pigs underwent a standardized hemorrhagic shock and resuscitation protocol to simulate battlefield injury with prolonged evacuation to definitive care in cold environments.

Metabolomics classifies phase of care and identifies risk for mortality in a porcine model of multiple injuries and hemorrhagic shock.

Background: Early recognition and intervention in hemorrhagic shock is essential to improved outcomes. However, the lack of robust diagnostic tools readily available to identify patients in the field inhibits the ability to provide timely intervention. Therefore, the development of a reliable prognostic indicator, such as a serum biomarker or a metabolic profile, has significant potential to improve far-forward trauma care.

Environmental hypothermia in porcine polytrauma and hemorrhagic shock is safe.

We have previously demonstrated survival benefit to induced hypothermia in a porcine model of controlled hemorrhagic shock simulating an associated delay to definitive care. In the current study, we wished to evaluate the effects of environmental hypothermia in a porcine model of hemorrhagic shock with the addition of polytrauma. Sixteen pigs were randomized to normothermic (39°C, n = 7) or hypothermic (34°C, n = 9) groups.

Analysis of biomarkers characteristic of porcine liver injury--from biomolecular logic gates to an animal model.

A biocatalytic cascade for the analysis of the simultaneous increase in the concentration of two biomarkers characteristic of liver injury (alanine transaminase, ALT, and lactate dehydrogenase, LDH) was tested on real samples acquired from an animal model (domestic pigs, Sus scrofa domesticus) suffering from traumatic liver injury. A two-step reaction biocatalyzed in the presence of both enzyme-biomarkers resulted in the oxidation of NADH followed by optical absorbance measurements. A simple qualitative, YES/NO, test allowed for distinction between animals with and without the presence of liver injury with the probability of 92%.

Hypercoagulability in porcine hemorrhagic shock is present early after trauma and resuscitation.

Introduction: The understanding of coagulopathy associated with trauma continues to evolve. Trauma patients are frequently coagulopathic early after injury and become hypercoagulable within days of injury. Thrombelastography (TEG) allows real-time evaluation of the coagulation status of patients.

Treatment with beta-hydroxybutyrate and melatonin is associated with improved survival in a porcine model of hemorrhagic shock.

Introduction: The neuroprotective ketone β-hydroxybutyrate (BHB) and the antioxidant melatonin have been found at elevated levels in hibernating mammals. Previous studies in rat models of hemorrhagic shock have suggested a benefit. We compared infusion of 4M BHB and 43 mM melatonin (BHB/M) to 4M sodium chloride and 20% DMSO (control solution) to evaluate for potential benefits in porcine hemorrhagic shock.

Liver metabolomic changes identify biochemical pathways in hemorrhagic shock.

Background: Despite ongoing advances in treatment, thousands of patients still die annually from complications due to hemorrhagic shock, a condition causing dramatic physiologic and metabolic changes as cells switch to anaerobic metabolism in response to oxygen deprivation. As the shift from aerobic to anaerobic metabolism occurs in the peripheral tissues during shock, the liver must increase production of endogenous glucose as well as process excess lactate produced in the periphery. This places the liver at the center of metabolic regulation in the body during hemorrhagic shock.

Hypothermia is associated with improved outcomes in a porcine model of hemorrhagic shock.

Background: : Hypothermia after trauma is, in current medical practice, both avoided and aggressively treated. However, the effects of environmental hypothermia during early resuscitation after hemorrhagic shock have been only poorly characterized.

Methods: : The objective of our study was to compare normothermia versus mild and severe levels of hypothermia in a porcine model of hemorrhagic shock.

Noninvasive tissue oxygen saturation measurements identify supply dependency.

Background: Hemorrhagic shock can lead to multiple organ failure and death. We have previously shown that noninvasive measurement of tissue oxygen saturation (StO(2)) has predictive value for outcomes in patients suffering hemorrhagic shock. Our study objectives were twofold: (1) to compare invasive and noninvasive measurements of local and systemic tissue hemoglobin oxygenation and (2) to compare the effects of various physiologic conditions seen in patients in hemorrhagic shock on tissue hemoglobin oxygenation.

Eight hours of hypotensive versus normotensive resuscitation in a porcine model of controlled hemorrhagic shock.

Objectives: The aim of this study was to compare hypotensive and normotensive resuscitation in a porcine model of hemorrhagic shock.

Methods: This was a prospective, comparative, randomized survival study of controlled hemorrhagic shock using 28 male Yorkshire-Landrace pigs (15 to 25 kg). In 24 splenectomized pigs, the authors induced hemorrhagic shock to a systolic blood pressure (sBP) of 48 to 58 mm Hg (approximately 35% bleed).

Near-infrared spectroscopy in patients with severe sepsis: correlation with invasive hemodynamic measurements.

Background: Clinicians have begun using near-infrared spectroscopy (NIRS) to monitor tissue perfusion in hemorrhagic shock, as the technique allows continuous noninvasive monitoring of tissue hemoglobin oxygen saturation (StO(2)) and the tissue hemoglobin index (THI). We hypothesized that StO(2) measurements in patients with severe sepsis would be associated with the severity of their illness and would correlate with invasive hemodynamic measurements.

Methods: We measured mean arterial pressure (MAP), serum lactate concentration, blood hemoglobin concentration, StO(2), and THI in nine healthy volunteers and ten patients with septic shock in a surgical intensive care unit (ICU).

Increased poly(ADP-ribose) polymerase activity during porcine hemorrhagic shock is transient and predictive of mortality.

Aim Of The Study: The aim of our study was to compare poly(ADP-ribose) polymerase (PARP) activity levels in a porcine model of hemorrhagic shock and resuscitation.

Materials And Methods: We designed a prospective, comparative randomized survival study of hemorrhagic shock using 20 male Yorkshire-Landrace pigs (15-25 kg). In 16 pigs after splenectomy, we induced hemorrhagic shock to a mean arterial pressure of 50 mm Hg ( approximately 35% bleed).

Dynamic near-infrared spectroscopy measurements in patients with severe sepsis.

This study evaluated near-infrared spectroscopy (NIRS)-derived measurements in hemodynamically stable patients with severe sepsis, as compared with similar measurements in healthy age-matched volunteers. Prospective, preliminary, observational study in a surgical intensive care unit and clinical research center at a university health center. We enrolled 10 patients with severe sepsis and 9 healthy age-matched volunteers.

Use of near-infrared spectroscopy in early determination of irreversible hemorrhagic shock.

Background: In field situations, patient triage may require early determination of patients progressing to irreversible shock. We investigated the utility of near-infrared spectroscopy (NIRS) in early detection of irreversible hemorrhagic shock.

Methods: Twenty instrumented pigs were treated with a protocol involving 35% blood volume hemorrhage, 90 minutes of shock, and stepwise resuscitation with lactated Ringer's.

Ringer's ethyl pyruvate in hemorrhagic shock and resuscitation does not improve early hemodynamics or tissue energetics.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of hemorrhagic shock. Ethyl pyruvate, a derivative of pyruvate and a proposed oxygen radical scavenger, is attractive as a possible resuscitation fluid. We investigated whether resuscitation with lactated Ringer's (LR) containing ethyl pyruvate (REP) had any hemodynamic or tissue energetic benefits compared with LR alone for hemorrhagic shock.