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Introduction
Publications
Publications (154)
BACKGROUND
Awareness of ventilator-induced lung injury contributed to increased use of extracorporeal interventions, but not immediately after injury, before acute respiratory distress syndrome (ARDS) ensues. Our objective was to evaluate the role of venovenous extracorporeal carbon dioxide removal (ECCO 2 R) in management of mechanically ventilate...
Introduction
Absence of pre-hospital coagulation tests challenges prompt management of hemostasis after trauma. The Viscoelastic Coagulation Monitor (VCM, Entegrion, Durham, NC) is a hand-held coagulation test for point-of-care. We evaluated VCM in a translational swine polytrauma model, hypothesizing that VCM correlates with a laboratory reference...
Background
Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting.
Methods
We sought to bridge this gap by linking preclinical data in a...
Microfluidic membrane oxygenators are designed to mimic branching vasculature of the native lung during extracorporeal lung support. To date, scaling of such devices to achieve clinically relevant blood flow and lung support has been a limitation. We evaluated a novel multilayer microfluidic blood oxygenator (BLOx) capable of supporting 750–800 ml/...
Objective:
Assess efficacy of immediate post-injury intravenous administration of autologous or allogeneic bone-marrow-derived mesenchymal stromal cells (MSCs) for treatment of ARDS due to smoke inhalation and burns.
Methods:
Yorkshire swine (n=32, 44.3±0.5 kg), underwent intravenous anesthesia, placement of lines, severe smoke inhalation and 40...
ARDS is one of the leading causes of high morbidity and mortality in trauma patients. Previously our data demonstrated autologous MSCs treatment improved survival in a swine model of smoke inhalation and burn injury. However, the pathophysiological mechanisms are still largely unknown.
Twenty anesthetized female swine underwent smoke inhalation inj...
Recent global events such as COVID‐19 pandemic amid rising rates of chronic lung diseases highlight the need for safer, simpler, and more available treatments for respiratory failure, with increasing interest in extracorporeal membrane oxygenation (ECMO). A key factor limiting use of this technology is the complexity of the blood circuit, resulting...
Coating all portions of an extracorporeal membrane oxygenation (ECMO) circuit with materials exhibiting inherent, permanent antithrombotic properties is an essential step to prevent thrombus-induced complications. However, developing antithrombotic coatings for oxygenator fibers within membrane oxygenators of ECMO systems has proven challenging. We...
Numerous biomaterials have been developed for application in blood‐contacting medical devices to prevent thrombosis; however, few materials have been applied to full‐scale devices and evaluated for hemocompatibility under clinical blood flow conditions. We applied a dual‐action slippery liquid‐infused (LI) nitric oxide (NO)‐releasing material modif...
Background
Patients with kidney failure are at risk for lethal complications from hyperkalemia. Resuscitation, medications, and hemodialysis are used to mitigate increased potassium (K ⁺ ) levels in circulating blood; however, these approaches may not always be readily available or effective, especially in a resource limited environment. We tested...
Medical devices that require substantial contact between blood and a foreign surface would be dramatically safer if constructed from materials that prevent clot formation and coagulation disturbance at the blood-biomaterial interface. Nitric oxide (NO), an endogenous inhibitor of platelet activation in the vascular endothelium, could provide antico...
Introduction
Clot formation, infection, and biofouling are unfortunate but frequent complications associated with the use of blood-contacting medical devices. The challenge of blood-foreign surface interactions is exacerbated during medical device applications involving substantial blood contact area and extended duration of use, such as extracorpo...
Background:
We assessed the use of an FDA-cleared transport ventilator with limited functions and settings during ground transport in a swine model of ground evacuation. We hypothesized that when used as an adjunct to extracorporeal life support (ECLS), the device would enable safe mobile ventilatory support during ground evacuation.
Methods:
Fe...
Background:
Consumption of platelets and coagulation factors during extracorporeal carbon dioxide removal (ECCO2 R) increases bleeding complications and associated mortality. Regional infusion of lactic acid enhances ECCO2 R by shifting the chemical equilibrium from bicarbonate to carbon dioxide. Our goal was to test if regional blood acidificatio...
Extracorporeal membrane oxygenation (ECMO) has been advancing rapidly due to a combination of rising rates of acute and chronic lung diseases as well as significant improvements in the safety and efficacy of this therapeutic modality. However, the complexity of the ECMO blood circuit, and challenges with regard to clotting and bleeding, remain as b...
Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remo...
Mechanical trauma to major arterial vessels often leads to significant vascular compromise to large tissue beds which then results in the immediate reduction in oxygen delivery, cellular dysoxia, and cell death. This occurs in varying degrees to every anatomic region and organ in the body. The degree and extent of tissue injury directly correlates...
Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remo...
Background
In this review, we assess the state of Resuscitative Endovascular Occlusion of the Aorta (REBOA) today with respect to out-of-hospital (OOH) vs. inhospital (H) use in blunt and penetrating trauma, as well as discuss areas of promising research that may be key in further advancement of REBOA applications.
Methods
To analyze the trends in...
Integrating spontaneous breathing into mechanical ventilation (MV) can speed up liberation from it and reduce its invasiveness. On the other hand, inadequate and asynchronous spontaneous breathing has the potential to aggravate lung injury. During use of airway-pressure-release-ventilation (APRV), the assisted breaths are difficult to measure. We d...
The recent emergence of microfluidic extracorporeal lung support technologies presents an opportunity to achieve high gas transfer efficiency and improved hemocompatibility relative to the current standard of care in extracorporeal membrane oxygenation (ECMO). However, a critical challenge in the field is the ability to scale these devices to clini...
Introduction:
Extracorporeal life support (ECLS) patients are at risk for complications caused by gaseous microemboli (GME). GMEs can cause hypoxia, inflammation, coagulation, and end-organ damage. The objective of this in vitro study was to assess dynamics of GME formation during circulation of whole blood or a glycerol blood surrogate. We hypoth...
Coagulopathic complications during extracorporeal life support (ECLS) result from two parallel processes: 1) foreign surface contact and shear stress during blood circulation and 2) administration of anticoagulant drugs to prevent circuit thrombosis. To address these problems, biocompatible surfaces are developed to prevent foreign surface-induced...
Extracorporeal cardiopulmonary resuscitation (ECPR) shows promise for the emergency care of trauma patients in cardiac arrest but is not a part of current trauma resuscitation guidelines. The recognition of new management patterns in the critical management of trauma is needed as well as justification of whether wider use of extracorporeal resuscit...
Background and objective
Resuscitative Endovascular Balloon Occlusion of Aorta (REBOA) has emerged as a potential life-saving maneuver for the management of non-compressible torso hemorrhage in trauma patients. Complete REBOA (cREBOA) is inherently associated with the burden of ischemia reperfusion injury (IRI) and organ dysfunction. However, the d...
Background:
Non-compressible torso hemorrhage (NCTH) is the leading cause of potentially preventable death on the battlefield. Resuscitative endovascular balloon occlusion of the aorta (REBOA) aims to restore central blood pressure and control NCTH below the balloon, but risks ischemia-reperfusion injury to distal organs when prolonged. We tested...
Medical device-associated bacterial infections remain a significant complication for patients on extracorporeal organ support. Device-specific bacterial infections occur when bacteria enter the host tissue and attach to the devices, enabling bacteria to colonize and multiply rapidly. Preventing bacterial attachment would efficiently inhibit coloniz...
Background:
We investigated the expression of high mobility group box 1 (HMGB1) protein in a combat-relevant polytrauma/ acute respiratory distress syndrome (ARDS) model. We hypothesized that systemic HMGB1 expression is increased after injury and during aeromedical evacuation (AE) at altitude.
Methods:
Female Yorkshire swine (n =15) were anesth...
Background:
Diagnosis of lung injury requires invasive blood draws to measure oxygen tension in blood. This capability is nonexistent in austere settings and during prolonged field care (PFC), that is, medical care characterized by inability to evacuate casualties from the point of injury for up to 72 hours. We analyzed pulse-oximeter-derived noni...
A new generation of extracorporeal artificial organ support technologies collectively known as extracorporeal life support (ECLS) devices are being developed for diverse applications to include acute support for trauma-induced organ failure, transitional support for bridge to organ transplant and terminal support for chronic diseases. Across applic...
Background:
Extracorporeal membrane oxygenation (ECMO) has frequent and sometimes lethal thrombotic complications. The role that activated platelets, leukocytes, and small (0.3-1 micron) extracellular vesicles (EVs) in ECMO thrombosis is not well understood.
Objectives:
To test the effect of blood flow rate on the generation of activated platele...
Background:
We investigated effects of mesenchymal stem cells (MSC) or low-flow extracorporeal life support (ECLS) as adjunctive treatments for acute respiratory distress syndrome (ARDS) due to inhalation injury and burns. We hypothesized that these interventions decrease histological end-organ damage.
Methods:
Anesthetized female swine underwen...
Coagulation management is the leading challenge during extracorporeal life support (ECLS) due to shear stress and foreign-surface-induced coagulation disturbance during circulation. A nonadhesive, liquid-infused coating called tethered liquid perfluorocarbon (TLP) was developed to prevent adhesion of blood on medical materials. We investigated the...
Burn injury initiates a hypermetabolic response leading to muscle catabolism and organ dysfunction but has not been well-characterized by high-throughput metabolomics. We examined changes in metabolism over the first 72 h post-burn using proton nuclear magnetic resonance (1H-NMR) spectroscopy and serum from a porcine model of severe burn injury. We...
Mesenchymal stem cells (MSCs) are a promising form of therapy for acute respiratory distress syndrome (ARDS). The objective of this study was two-fold: (a) to characterize cytokine expression in serum from ARDS subjects receiving MSCs and (b) to determine MSC function following "preconditioning" with ARDS serum. In phase I, serum from three cohorts...
Aim: In this study, we aimed at identifying the optimal conditions for isolation, processing and expansion of mesenchymal stem cells (MSCs). Methods: Porcine bone marrow was obtained from either small- or large-volume bone marrow aspirate (BMA). Next, three BMA processing methods were compared. Finally, the best condition was selected from various...
Hemocompatible materials for extracorporeal life support (ECLS) technology are investigated to mitigate thrombotic complications associated with this therapy. A promising solution is an omniphobic bilayer coating, tethered liquid perfluorocarbon (TLP), which utilizes an immobilized tether to anchor a mobile, liquid surface lubricant that prevents a...
Background:
Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury with a mortality rate of up to 40%. Early management of ARDS has been difficult due to the lack of sensitive imaging tools and robust analysis software. We previously designed an optical coherence tomography (OCT) system to evaluate mucosa thickness (MT) a...
Background:
Coagulation monitoring capabilities during transport are limited. Thromboelastography (TEG) is a whole-blood clotting test measuring clot formation, stabilization and fibrinolysis; and is traditionally performed in a laboratory. We evaluated a new point-of-care TEG analyzer, TEG 6s (Haemonetics; Braintree, MA), in a large animal model...
Background:
Smoke inhalation injury (SII) causes 30% to 40% mortality and will increase as a cause of death during prolonged field care. We used a combat relevant model of acute respiratory distress syndrome due to SII to study temporal changes in ventilation-perfusion (V/Q) matching, computed tomography (CT) scan data, and histopathology and hypo...
Patent application for a treatment system to deliver breathing gas and frozen stem cells or other biologics.
Multipotent mesenchymal stem/stromal cells (MSCs) possess robust self-renewal characteristics and the ability to differentiate into tissue-specific cells. Their therapeutic potential appears promising as evident from their efficacy in several animal models of pulmonary disorders as well as early-phase clinical trials of acute respiratory distress s...
Background:
The prevalence of acute respiratory distress syndrome (ARDS) in mechanically ventilated burn patients is 33%, with mortality varying from 11-46% depending on ARDS severity. Despite the new Berlin definition for ARDS, prompt bedside diagnosis is lacking. We developed and tested a bedside technique of fiberoptic-bronchoscopy-based optica...
Background:
It is known that, following a physiological insult, bone marrow-derived mesenchymal stem cells (MSCs) mobilize and home to the site of injury. However, the effect of injury on the function of endogenous MSCs is unknown. In this study, MSCs harvested from the bone marrow of swine with or without acute respiratory distress syndrome (ARDS...
Background:
Management of hemostasis is a key challenge during extracorporeal life support (ECLS). Metal organic frameworks are being investigated for use as nitric oxide (NO) catalysts for incorporation into ECLS circuitry to prevent thrombosis at the blood-biomaterial interface. A specific metal organic framework, CuBTTri, has been shown to acce...
Advanced extracorporeal therapies have been successfully applied in the austere environment of combat casualty care over the previous decade. In this review, we describe the historic underpinnings of extracorporeal membrane oxygenation (ECMO), review the recent experience with both partial and full lung support during combat operations, and critica...
This review describes the current state of the science on mesenchymal stem cell (MSC) treatment for acute lung injury (ALI). The general characteristics, regenerative potential, and mechanism of action of MSCs are first presented. Next, particular emphasis is placed on the application of MSCs for the treatment of acute respiratory distress syndrome...
Background. One of the most plentiful sources for MSCs is the bone marrow; however, it is unknown whether MSC yield differs among different bone marrow sites. In this study, we quantified cellular yield and evaluated resident MSC population from five bone marrow sites in the porcine model. In addition, we assessed the feasibility of a commercially...
Background:
Smoke inhalation and burn injury remain a major source of morbidity and mortality. There is known dysregulation of hemostasis in burn patients, but either hyper- or hypocoagulation states are reported. Sheep are an established animal model for studying burn pathology and provide robust data on hemostatic function at baseline and after...
Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been classically employed as a rescue therapy for patients with respiratory failure not treatable with conventional mechanical ventilation alone. In recent years, however, the timing of ECMO initiation has been readdressed and ECMO is often started earlier in the time course of respirator...
Extracorporeal life support (ECLS) is fast becoming more common place for use in adult patients failing mechanical ventilation. Management of coagulation and thrombosis has long been a major complication in the use of ECLS therapies. Scanning electron microscopy (SEM) of membrane oxygenators (MO) after use in ECLS circuits can offer novel insight i...
The Multiple Inert Gas Elimination Technique (MIGET) is a method of assessing ventilation/perfusion (VA/Q) inequalities, shunt, and diffusion limitation. It was initially developed as a means of quantifying VA/Q mismatch as an intrapulmonary cause of hypoxemia. The lung is viewed as a set of 50 respiratory units, each with a distinctive VA/Q ratio....
Background:
The authors studied the effects on membrane lung carbon dioxide extraction (VCO2ML), spontaneous ventilation, and energy expenditure (EE) of an innovative extracorporeal carbon dioxide removal (ECCO2R) technique enhanced by acidification (acid load carbon dioxide removal [ALCO2R]) via lactic acid.
Methods:
Six spontaneously breathing...
Introduction:
In thermally injured patients, inhalation injury is often associated with acute respiratory distress syndrome (ARDS), and is an independent predictor of increased morbidity and mortality. Extracorporeal CO2 removal (ECCO2R) therapy offers new possibilities in protective mechanical ventilation in ARDS patients. We performed an early a...
Purpose:
End-tidal CO2 (eTCO2) can be used to estimate the arterial CO2 (PaCO2) under steady-state conditions, but that relationship deteriorates during hemodynamic or respiratory instability. We developed a multivariate method to improve our ability to estimate the PaCO2, by using additional information contained in the volumetric capnograph (Vca...
Introduction:
Host inflammatory response to any form of tissue injury, including burn, trauma, or shock has been well documented. After significant burns, cytokines can increase substantially within the first 24 hours after injury and may contribute to subsequent organ failure. Hemoadsorption by cytokine-adsorbing columns may attenuate this malada...
Over 32% of burned battlefield causalities develop trauma-induced hypoxic respiratory failure, also known as acute respiratory distress syndrome (ARDS). Recently, nine out of ten US combat soldiers' survived life threatening trauma-induced ARDS supported with extracorporeal membrane oxygenation (ECMO), a portable form of cardiopulmonary bypass. Unf...
BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is less invasive than emergency department thoracotomy for the treatment of massive hemorrhage. We evaluated the effects of REBOA on carotid blood flow (Qcarotid) in a porcine model of massive hemorrhage. We hypothesized that REBOA restores Qcarotid faster than reinfusion...
Acidification of blood entering a membrane lung (ML) with lactic acid enhances CO2 removal (VCO2ML). We compared the effects of infusion of acetic, citric and lactic acids on VCO2ML. Three sheep were connected to a custom-made circuit, consisting of a Hemolung device (Alung Technologies, Pittsburgh, PA), a hemofilter (NxStage, NxStage Medical, Lawr...
A prolonged and fulminant inflammatory state, with high levels of pro- and anti-inflammatory mediators, is seen after extensive thermal injury. Blood purification techniques including plasma exchange, continuous venovenous hemofiltration, and adsorbing membranes have the potential to modulate this response, thereby improving outcomes. This article...
Background:
Recently, automated alerts have been used to identify patients with respiratory failure based on set criteria, which can be gleaned from the electronic medical record (EMR). Such an approach may also be useful for identifying patients with severe adult respiratory distress syndrome (ARDS) who may benefit from extracorporeal membrane ox...
Purpose:
Compare virtual bronchoscopy (VB) to fiberoptic bronchoscopy (FOB) for scoring smoke inhalation injury (SII).
Methods:
Swine underwent computerized tomography (CT) with VB and FOB before (0) and 24 and 48 h after SII. VB and FOB images were scored by 5 providers off line.
Results:
FOB and VB scores increased over time (p<0.001) with F...
: Toxic epidermal necrolysis (TEN) is a rare condition affecting an estimated 1 to 2 cases per million per year, with reported mortality between 30% and 50% typically because of multiorgan failure or sepsis. Acute pulmonary complications from this disorder include bronchial mucosal sloughing, pulmonary edema, and infectious pneumonitis. Pulmonary c...
Hemorrhagic shock (HS) is a setting in which both pulmonary and cutaneous perfusion may be impaired. The goals of this study were (1) to evaluate the relationship between end-tidal (etCO2), transcutaneous (tPCO2), arterial carbon dioxide (PaCO2), and lactate during lethal HS; and (2) to assess the effect of progressive HS on those variables and on...
The combination of extracorporeal carbon dioxide removal (ECCO2R) and hemofiltration is a possible therapeutic strategy for patients needing both lung and renal support. We tested the effects of the recirculation of ultrafiltrate on membrane lung (ML) CO2 removal (VCO2ML).Three conscious, spontaneously breathing sheep were connected to a commercial...