Cellular Cytosolic Energy Replenishment Increases Vascularized Composite Tissue Tolerance to Extended Cold Ischemia Time.

Background: Vascularized composite allotransplantation (VCA) is a restorative surgical procedure to treat whole or partially disfiguring craniofacial or limb injuries. The routine clinical use of this VCA surgery is limited using compromised allografts from deceased donors and by the failure of the current hypothermic preservation protocols to extend the allograft's cold ischemia time beyond 4 h. We hypothesized that the active replenishment of the cellular cytosolic adenosine-5`-triphosphate (ATP) stores by means of energy delivery vehicles (ATPv) encapsulating high-energy ATP is a better strategy to improve allograft's tolerance to extended cold ischemia times.

Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly.

Peritoneal dialysis solution (PDS) dilates peritoneal microvessels predominantly by the activation of the endothelial nitric oxide (NO) pathway. We made an incidental observation of decreased PDS-induced, NO-dependent peritoneal microvascular vasoreactivity in elderly rats naïve to PDS exposure. We hypothesized that this subordinate NO-mediated peritoneal microvascular vasoreactivity is caused by increased oxidative stress in the aged endothelium, which compromises NO bioavailability in the elderly, and that peritoneal microvascular vasoreactivity can be improved by the supplementation of antioxidant glycine to PDS.

Propranolol attenuates cognitive, learning, and memory deficits in a murine model of traumatic brain injury.

Background: β-blockers have been shown to improve survival after traumatic brain injury (TBI); however, the impact of continuous dosage of β-blockers on cognitive function has not been elucidated. We hypothesized that a daily dose of propranolol can improve memory, learning, and cognitive function following TBI.

Study Design: Twenty male C57BL mice were subjected to a cortical-controlled moderate TBI.

The acute inflammatory response after trauma is heightened by frailty: A prospective evaluation of inflammatory and endocrine system alterations in frailty.

Background: Frailty is a geriatric syndrome characterized by decreased physiological reserves, increased inflammation, and decreased anabolic-endocrine response. The biomarkers associated with frailty are poorly understood in trauma. The aim of this study was to analyze the association between frailty and immune: IL-1β, IL-6, IL-2Rα, tumor necrosis factor (TNF)-α, and endocrine biomarkers: insulin-like growth factor-1 and growth hormone in trauma patients.

Outcomes After Massive Transfusion in Trauma Patients: Variability Among Trauma Centers.

Background: Exsanguinating trauma patients often require massive blood transfusion (defined as transfusion of 10 or more pRBC units within first 24 h). The aim of our study is to assess the outcomes of trauma patients receiving massive transfusion at different levels of trauma centers.

Methods: Two-y (2013-2014) retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program.

Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin for Thromboprophylaxis in Nonoperative Pelvic Fractures.

Background: Patients with pelvic fractures are prone to venous thromboembolic (VTE) complications. Recent literature shows superiority of direct oral anticoagulants (DOACs) over low-molecular-weight heparin (LMWH) for thromboprophylaxis in patients undergoing orthopaedic operations. The aim of our study was to compare in-hospital outcomes for DOACs vs LMWH in patients with nonoperative pelvic fractures.

The burden of excess length of stay in trauma patients.

Background: Disposition of trauma patients frequently results in excessive hospital-stay. The aim of this study was to assess the risk of developing complications due to excessive stay in the hospital.

Methods: Over a period of 4 years (2012-2015) we analyzed all trauma patients with hospital length-of-stay (h-LOS) >30 days.

3-Factor Versus 4-Factor PCC in Coagulopathy of Trauma: Four is Better Than Three.

Introduction: Coagulopathy of trauma (COT) is common and highly lethal. Prothrombin complex concentrate (PCC) has been advocated for correction of COT. However, the difference in efficacy between three-factor PCC (3-PCC) versus four-factor PCC (4-PCC) remains unclear.

The novel oral anticoagulants (NOACs) have worse outcomes compared with warfarin in patients with intracranial hemorrhage after TBI.

Introduction: Novel oral anticoagulant (NOAC) use is increasing in trauma patients. The reversal of these agents after hemorrhage is still evolving. The aim of our study was to evaluate outcomes after traumatic brain injury in patients on NOACs.

The role of four-factor prothrombin complex concentrate in coagulopathy of trauma: A propensity matched analysis.

Background: Coagulopathy is a common complication after severe trauma. The efficacy of 4-factor prothrombin complex concentrate (4-PCC) as an adjunct to fresh frozen plasma (FFP) in reversal of coagulopathy of trauma (COT) has not been studied. The aim of our study is to compare 4-PCC + FFP versus FFP alone for the treatment of COT.

Continuous remote ischemic conditioning attenuates cognitive and motor deficits from moderate traumatic brain injury.

Background: While studies show that single-dose remote ischemic conditioning (RIC) improves outcomes, the effect of continuous (daily) RIC is unknown. Thus, we aimed to investigate the role of continuous RIC on cognitive and motor function following traumatic brain injury (TBI).

Methods: We subjected 24 male C57BL mice to a cortical-controlled TBI.

Perioperative glycemic control and postoperative complications in patients undergoing emergency general surgery: What is the role of Plasma Hemoglobin A1c?

Background: Plasma hemoglobin A1c (HbA1c) reflects quality of glucose control in diabetic patients. Literature reports that patients undergoing surgery with an elevated HbA1c level are associated with increased postoperative morbidity and mortality. The aim of our study was to evaluate the impact of HbA1c level on outcomes after emergency general surgery (EGS).

Molecular mechanisms of peritoneal dialysis-induced microvascular vasodilation.

Peritoneal dialysis (PD) solutions dilate microvessels by undefined mechanisms. This vasodilation directly affects ultrafiltration and solute exchange during a PD dwell and is thought to account for the variable mass transfer area coefficient for small solutes during a glucose-based hypertonic dwell. We hypothesized that PD-mediated vasodilation occurs by endothelium-dependent mechanisms that involve endothelium energy-dependent K+ channels (K(ATP)), adenosine A1 receptor activation, and NO release.

Hyperosmolality-mediated peritoneal microvascular vasodilation is linked to aquaporin function.

Glucose-based peritoneal dialysis (PD) solutions dilate the parietal and visceral peritoneal microvasculature by endothelium-dependent mechanisms that primarily involve hyperosmolality. This PD-mediated dilation occurs by active intracellular glucose uptake and adenosine Al receptor activation, and by hyperosmolality-stimulated glibenclamide-sensitive potassium channels. Both pathways invoke NO as a second messenger for vasodilation.

Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock.

Conventional resuscitation (CR) from hemorrhagic shock (HS) results in gut and liver hypoperfusion, organ and cellular edema, and vital organ injury. Adjunct direct peritoneal resuscitation (DPR) with dialysate prevents gut vasoconstriction, hypoperfusion, and injury. We hypothesized that DPR might also improve hepatocellular edema, inflammation, and injury.

Glucose-induced intestinal vasodilation via adenosine A1 receptors requires nitric oxide but not K(+)(ATP) channels.

Background: Both nitric oxide (NO) and adenosine A1 receptor activation mediate microvascular vasodilation during intestinal glucose absorption. Our overall hypothesis is that adenosine triphosphate (ATP) utilization during glucose absorption would increase adenosine metabolite release, which acts on adenosine A1 receptors to alter endothelial production of NO and/or activate ATP-dependent potassium channels (K(+)(ATP)) to dilate intestinal microvessels.

Methods: Intravital videomicroscopy of the rat jejunum was used to record the vascular responses of inflow (termed 1A) arterioles, proximal (p3A), and distal (d3A) premucosal arterioles during exposure to isotonic glucose or mannitol solutions alone or in the presence of the selective nitric oxide synthase (NOS) inhibitor (L-NMMA), an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), or a K(+)(ATP) channel inhibitor (glibenclamide).

Hemorrhage-induced hepatic injury and hypoperfusion can be prevented by direct peritoneal resuscitation.

Background: Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes).

Plasma appearance rate of intraperitoneal macromolecular tracer underestimates peritoneal lymph flow.

The magnitude of peritoneal lymph flow is an issue of great controversy in peritoneal dialysis (PD) research. Because no single lymphatic duct drains the entire peritoneal cavity, peritoneal lymph flow is indirectly measured as lymphatic removal of intraperitoneal macromolecular tracer. In rats, the peritoneal clearance (K) of such a tracer is 5 times the approximately 8 microL/min determined from the tracer appearance rate in blood (Cl).

Chronic infusion of sterile peritoneal dialysis solution abrogates enhanced peritoneal gene expression responses to chronic peritoneal catheter presence.

Chronic exposure to sterile peritoneal dialysis (PD) solutions is associated with microvascular and interstitial changes within the blood-peritoneal barrier (peritoneum). These changes are commonly linked to loss of peritoneal function over time, presumably because of angiogenesis-related increased vascular area. However, the effects on peritoneal microvascular function of chronic peritoneal exposure to PD solutions are unknown.

Vasoactive components of dialysis solution.

Background: Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components causing such vasoactivity are still controversial. This study was conducted to define the vasoactive components of conventional and new PD solutions.

Hemorrhagic shock and resuscitation-mediated tissue water distribution is normalized by adjunctive peritoneal resuscitation.

Background: Adjunctive direct peritoneal resuscitation (DPR) from hemorrhagic shock (HS) improves intestinal blood flow and abrogates postresuscitation edema. HS causes water shifts as a result of sodium redistribution and changes in transcapillary Starling forces. Conventional resuscitation (CR) with crystalloid aggravates water sequestration.

Cellular edema regulates tissue capillary perfusion after hemorrhage resuscitation.

Background: Hemorrhage-induced activation of endothelial cell Na+/H+ -exchanger results in cellular swelling, which physically impedes capillary filling and compromises gut perfusion. We hypothesized that correction of the vascular volume deficit by conventional resuscitation does not improve capillary filling unless cellular swelling is prevented. Also, we hypothesized that adjunctive direct peritoneal resuscitation (DPR) with topical peritoneal dialysis solution (Delflex; Fresenius USA, Inc.

Postresuscitation tissue neutrophil infiltration is time-dependent and organ-specific.

Background: Hemorrhagic shock with conventional resuscitation (CR) primes circulating neutrophils and activates vascular endothelium for increased systemic inflammation, superoxide release, and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) with intraperitoneal instillation of a clinical peritoneal dialysis solution decreases systemic inflammation and edema formation by enhancing tissue perfusion. The aim of this study is to determine the effect of adjunctive DPR on neutrophil and fluid sequestration.

Mechanisms of direct peritoneal resuscitation-mediated splanchnic hyperperfusion following hemorrhagic shock.

Conventional resuscitation (CR) from hemorrhagic shock causes a persistent and progressive splanchnic vasoconstriction and hypoperfusion despite hemodynamic restoration with intravenous fluid therapy. Adjunctive direct peritoneal resuscitation (DPR) with a clinical peritoneal dialysis solution instilled into the peritoneal cavity has been shown to restore splanchnic tissue perfusion, down-regulate the gut-derived exaggerated systemic inflammatory response, promote early fluid mobilization, and improve overall outcome. This study was conducted to define the molecular mechanisms of DPR-induced gut hyperperfusion after hemorrhagic shock.

Role of adenosine receptor subtypes in rat jejunum in unfed state versus glucose-induced hyperemia.

Background: Adenosine is a key mediator in intestinal absorptive hyperemia. This study examines the role of adenosine receptor subtypes in the intestinal microvasculature at rest (unfed) and during glucose exposure.

Materials And Methods: Intravital video microscopy was used to record vascular responses in the rat jejunum in unfed resting states versus active glucose absorption.