Metabolic Tissue Swelling and Local Microcirculation in Splanchnic Artery Occlusion Shock: Implications for Critical Illness.

Trauma is a leading cause of death in the United States. Advancements in shock resuscitation have been disappointing because the correct upstream mechanisms of injury are not being targeted. Recently, significant advancements have been shown using new cell-impermeant molecules that work by transferring metabolic water from swollen ischemic cells to the capillary, which restores tissue perfusion by microcirculatory decompression.

Restoring microcirculatory perfusion in a preclinical model of severe hemorrhagic shock: The role of microcirculatory function.

Background: No reflow in capillaries (no reflow) is the lack of tissue perfusion that occurs once central hemodynamics are restored. This prevents oxygen transfer and debt repayment to vital tissues after shock resuscitation. Since metabolic swelling of cells and tissues can cause no reflow, it is a target for study in shock.

Effects of polyethylene glycol-20k IV solution on donor management in a canine model of donor brain death.

Background: Traditionally, vasopressors and crystalloids have been used to stabilize brain dead donors; however, the use of crystalloid is fraught with complications. This study aimed to investigate the effectiveness of a newly developed impermeant solution, polyethylene glycol-20k IV solution (PEG-20k) for resuscitation and support of brain dead organ donors.

Methods: Brain death was induced in adult beagle dogs and a set volume of PEG-20k or crystalloid solution was given thereafter.

Perioperative outcomes of inpatient laparoscopic Heller myotomy and per-oral endoscopic myotomy in the United States.

Background: Per-oral endoscopic myotomy is an alternative to pneumatic dilation and laparoscopic Heller myotomy to treat lower esophageal sphincter diseases. Laparoscopic Heller myotomy and per-oral endoscopic myotomy perioperative outcomes data come from relatively small retrospective series and 1 randomized trial. We aimed to estimate the number of inpatient procedures performed in the United States and compare perioperative outcomes and costs of laparoscopic Heller myotomy and per-oral endoscopic myotomy using a nationally representative database.

Exogenous Nicotinamide Adenine Dinucleotide Attenuates Postresuscitation Myocardial and Neurologic Dysfunction in a Rat Model of Cardiac Arrest.

Objectives: To investigate the therapeutic potential and underlying mechanisms of exogenous nicotinamide adenine dinucleotide+ on postresuscitation myocardial and neurologic dysfunction in a rat model of cardiac arrest.

Design: Thirty-eight rats were randomized into three groups: 1) Sham, 2) Control, and 3) NAD. Except for the sham group, untreated ventricular fibrillation for 6 minutes followed by cardiopulmonary resuscitation was performed in the control and NAD groups.

High-resolution respirometry for evaluation of mitochondrial function on brain and heart homogenates in a rat model of cardiac arrest and cardiopulmonary resuscitation.

The physiology and physiopathology process of mitochondrial function following cardiac arrest remains poorly understood. We aimed to assess mitochondrial respiratory function on the heart and brain homogenates from cardiac arrest rats. The expression level of SIRT1/PGC-1α pathway was measured by immunoblotting.

Cholangiocyte Epithelial to Mesenchymal Transition (EMT) is a potential molecular mechanism driving ischemic cholangiopathy in liver transplantation.

Donation after circulatory death (DCD) has expanded the donor pool for liver transplantation. However, ischemic cholangiopathy (IC) after DCD liver transplantation causes inferior outcomes. The molecular mechanisms of IC are currently unknown but may depend on ischemia-induced genetic reprograming of the biliary epithelium to mesenchymal-like cells.

Regulation of bladder dynamic elasticity: a novel method to increase bladder capacity and reduce pressure using pulsatile external compressive exercises in a porcine model.

Purpose: Dynamic elasticity is a biomechanical property of the bladder in which muscle compliance can be acutely adjusted through passive stretches and reversed with active contractions. The aim of this study was to determine if manipulating dynamic elasticity using external compression could be used as a novel method to acutely increase bladder capacity and reduce bladder pressure in a porcine model.

Methods: Ex vivo experiment: bladders underwent continuous or pulsatile compression after establishing a reference pressure at bladder capacity.

Polyethylene glycol-20k reduces post-resuscitation cerebral dysfunction in a rat model of cardiac arrest and resuscitation: A potential mechanism.

Out-of-hospital cardiac arrest (CA) is a leading cause of death in the United States. Severe post-resuscitation cerebral dysfunction is a primary cause of poor outcome. Therefore, we investigate the effects of polyethylene glycol-20k (PEG-20k), a cell impermeant, on post-resuscitation cerebral function.

Combined Therapy With Polyethylene Glycol-20k and MCC950 Preserves Post-Resuscitated Myocardial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation.

Background To investigate the therapeutic potential of combined therapy with polyethylene glycol-20k (PEG-20k) and MCC950 on post-resuscitation myocardial function in a rat model of cardiac arrest. Methods and Results Thirty rats were randomized into 5 groups: Sham, Control, PEG-20k, MCC950, PEG-20k+ MCC950. Except for sham, animals were subjected to 6 minutes of ventricular fibrillation followed by 8 minutes cardiopulmonary resuscitation.

Superior Survival Outcomes of a Polyethylene Glycol-20k Based Resuscitation Solution in a Preclinical Porcine Model of Lethal Hemorrhagic Shock.

Objective: To compare early outcomes and 24-hour survival after LVR with the novel polyethylene glycol-20k-based crystalloid (PEG-20k), WB, or hextend in a preclinical model of lethal HS.

Background: Posttraumatic HS is a major cause of preventable death. current resuscitation strategies focus on restoring oxygen-carrying capacity (OCC) and coagulation with blood products.

Temperature and flow rate limit the optimal ex-vivo perfusion of the heart - an experimental study.

Background: Ex-vivo heart perfusion can be utilized to study a variety of physiologic and molecular pathways in a controlled system outside of the body. It can also be used in clinical settings such as for organ preservation before transplantation. Myocardial oxygen consumption (MVO) correlates with energy production in the myocardium and can also be used to determine the balance between the oxygen supply and demand of the perfused heart.

Effects of Polyethylene Glycol-20k on Coronary Perfusion Pressure and Postresuscitation Myocardial and Cerebral Function in a Rat Model of Cardiac Arrest.

Background Epinephrine increases the rate of return of spontaneous circulation. However, it increases severity of postresuscitation myocardial and cerebral dysfunction and reduces duration of survival. We investigated the effects of aortic infused polyethylene glycol, 20 000 molecular weight (PEG-20k) during cardiopulmonary resuscitation on coronary perfusion pressure, postresuscitation myocardial and cerebral function, and duration of survival in a rat model of cardiac arrest.

Medication Reconciliation and Patient Safety in Trauma: Applicability of Existing Strategies.

The Joint Commission has established medication reconciliation as a National Patient Safety Goal, but it has not been studied much in trauma even though it is integral to safe patient care. This article reviews the existing medication reconciliation strategies and their applicability to the trauma setting. To perform medication reconciliation, hospitals use a variety of strategies including pharmacists or pharmacy technicians, electronic medical record tools, and patient-centered strategies.

Effects of a novel low volume resuscitation solutions on coagulation and platelet function.

Background: Novel crystalloid solutions containing polyethylene glycol polymers (PEG-20k) produce dramatic resuscitation effects but dose-dependently produce a hypocoagulative state. The objective of this study was to examine possible mechanisms of this effect. Based on previous thromboelastography data, we hypothesize the effect is largely due to platelet interactions with the polymers.

Acute resuscitation with polyethylene glycol-20k: A thromboelastographic analysis.

Background: Previous ex vivo studies have shown that polyethylene glycol-20,000 Da (PEG-20k), a novel synthetic polymer that is highly effective for resuscitation, has a hypocoagulable effect on human blood. This study's objective was to determine the in vivo effects of PEG-20k-based resuscitation solutions on coagulation and platelet function in a porcine model of hemorrhagic shock.

Methods: Anesthetized pigs underwent controlled hemorrhage until the lactate reached 7 mmol/L or 50% to 55% of their estimated blood volume was removed.

Thromboelastographic analysis of novel polyethylene glycol based low volume resuscitation solutions.

Background: Low volume resuscitation (LVR) in shock prevents deleterious effects of crystalloid loading in pre-hospital settings. Polyethylene glycol 20,000 (PEG-20k) based LVR solutions are 20-fold more effective at maintaining perfusion and survival in shock compared to conventional crystalloids. The aim of this study was to determine coagulation and platelet function of whole blood treated with 10% PEG-20k.

Effects of Polyethylene Glycol-20k on Postresuscitation Myocardial and Cerebral Function in a Rat Model of Cardiopulmonary Resuscitation.

Objectives: Polyethylene glycol-20k is a hybrid cell impermeant that reduces ischemia injury and improves microcirculatory flow during and following low flow states through nonenergy-dependent water transfer in the microcirculation. We investigated the effects of polyethylene glycol-20k on postresuscitation microcirculation, myocardial and cerebral function, and duration of survival in a rat model of cardiopulmonary resuscitation.

Design: Ventricular fibrillation was induced in 20 male Sprague Dawley rats and untreated for 6 minutes.

Low-Volume Resuscitation for Hemorrhagic Shock: Understanding the Mechanism of PEG-20k.

Hemorrhagic shock leads to cell and tissue swelling and no reflow from compressed capillaries. Cell impermeants, including polyethylene glycol-20,000 (PEG-20k), reverse ischemia-induced cell swelling, extend low-volume resuscitation (LVR) time after shock, and increase tolerance to the low-volume state. The purpose of this study was to explore the mechanisms of action of PEG-20k containing LVR solutions.

Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D Culture into Hepatocyte-like Cells through Direct Wnt/β-catenin Pathway Inhibition.

Treatment of acute liver failure by cell transplantation is hindered by a shortage of human hepatocytes. Current protocols for hepatic differentiation of human induced pluripotent stem cells (hiPSCs) result in low yields, cellular heterogeneity, and limited scalability. In the present study, we have developed a novel multicellular spheroid-based hepatic differentiation protocol starting from embryoid bodies of hiPSCs (hiPSC-EBs) for robust mass production of human hepatocyte-like cells (HLCs) using two novel inhibitors of the Wnt pathway.

Low-volume resuscitation using polyethylene glycol-20k in a preclinical porcine model of hemorrhagic shock.

Introduction: Polyethylene glycol-20k (PEG-20k) is highly effective for low-volume resuscitation (LVR) by increasing tolerance to the low-volume state. In our rodent shock model, PEG-20k increased survival and expanded the "golden hour" 16-fold compared to saline. The molecular mechanism is largely attributed to normalizations in cell and tissue fluid shifts after low-flow ischemia resulting in efficient microvascular exchange.

Donor gluconate rescues livers from uncontrolled donation after cardiac death.

Background: Ischemia from organ preservation or donation causes cells and tissues to swell owing to loss of energy-dependent mechanisms of control of cell volume. These volume changes cause substantial preservation injury, because preventing these changes by adding cell impermeants to preservation solutions decreases preservation injury. The objective of this study was to assess if this effect could be realized early in uncontrolled donation after cardiac death (DCD) livers by systemically loading donors with gluconate immediately after death to prevent accelerated swelling injury during the warm ischemia period before liver retrieval.

New low-volume resuscitation solutions containing PEG-20k.

Background: Hypovolemic shock reduces oxygen delivery and compromises energy-dependent cell volume control. Consequent cell swelling compromises microcirculatory flow, which reduces oxygen exchange further. The importance of this mechanism is highlighted by the effectiveness of cell impermeants in low-volume resuscitation (LVR) solutions in acute studies.

Transplantation of human stem cell-derived hepatocytes in an animal model of acute liver failure.

Introduction: Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotransplant model of ALF.

Methods: Intraperitoneal d-galactosamine was used to develop a lethal model of ALF in the rat.