Detection of occult hemorrhage using multivariate non-invasive technologies: a porcine study.

Occult hemorrhage (OH) can emerge subtly post-trauma, especially when internal bleeding is not yet severe enough to result in noticeable hemodynamic changes or shock. Despite normal appearances of traditional vital signs like heart rate (HR) and blood pressure (BP), clinically significant OH may be present, posing a critical diagnostic challenge. Early detection of OH, before vital signs begin to deteriorate, is vital as delays in identifying such conditions are linked to poorer patient outcomes.

Detection of subclinical hemorrhage using electrical impedance: a porcine study.

Analyze the performance of electrical impedance tomography (EIT) in an innovative porcine model of subclinical hemorrhage and investigate associations between EIT and hemodynamic trends.. Twenty-five swine were bled at slow rates to create an extended period of subclinical hemorrhage during which the animal's heart rate (HR) and blood pressure (BP) remained stable from before hemodynamic deterioration, where stable was defined as <15% decrease in BP and <20% increase in HRi.

Epinephrine plus chest compressions is superior to epinephrine alone in a hypoxia-induced porcine model of pseudo-pulseless electrical activity.

Aim: Pseudo-pulseless electrical activity (pseudo-PEA) is a global hypotensive ischemic state with retained coordinated myocardial contractile activity and an organized ECG with no clinically detectable pulses. The role of standard external chest compressions (CPR) and its associated intrinsic hemodynamics remains unclear in the setting of pseudo-PEA. We undertook an experimental trial to compare epinephrine alone versus epinephrine with CPR in the treatment of pseudo-PEA.

Intravenous calcium as a pressor in a swine model of hypoxic pseudo-pulseless electrical mechanical activity-a preliminary report.

Background: Pseudo-pulseless electrical activity (pseudo-PEA) is a lifeless form of profound cardiac shock characterized by measurable cardiac mechanical activity without clinically detectable pulses. Pseudo-PEA may constitute up to 40% of reported cases of cardiac arrest. Resuscitation from pseudo-PEA is often associated with hypotension refractory to catecholamine pressors.

Quantitative evaluation of the in vivo biocompatibility and performance of freeze-cast tissue scaffolds.

Quantitative methods are little used for the in vivo assessment of tissue scaffolds to evaluate biocompatibility. To complement current histological techniques, we introduce as a measure of biocompatibility a straightforward, geometric analysis for the quantitative assessment of encapsulation thickness, cross-sectional area, and biomaterial shape. Advantages of this new technique are that it enables, on the one hand, a more complete and objective comparison of scaffolds with differing compositions, architectures, and mechanical properties, and, on the other, a more objective approach to their selection for a given application.

Design, Manufacture, and Testing of a Tissue Scaffold for Permanent Female Sterilization by Tubal Occlusion.

Current FDA-approved permanent female sterilization procedures are invasive and/or require the implantation of non-biodegradable materials. These techniques pose risks and complications, such as device migration, fracture, and tubal perforation. We propose a safe, non-invasive biodegradable tissue scaffold to effectively occlude the Fallopian tubes within 30 days of implantation.

Treatment of Canine Oral Melanoma with Nanotechnology-Based Immunotherapy and Radiation.

The presence and benefit of a radiation therapy-associated immune reaction is of great interest as the overall interest in cancer immunotherapy expands. The pathological assessment of irradiated tumors rarely demonstrates consistent immune or inflammatory response. More recent information, primarily associated with the "abscopal effect", suggests a subtle radiation-based systemic immune response may be more common and have more therapeutic potential than previously believed.

Hypo-fractionated Radiation, Magnetic Nanoparticle Hyperthermia and a Viral Immunotherapy Treatment of Spontaneous Canine Cancer.

It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component. Two tumors received all three therapeutic modalities, one tumor received radiation and hyperthermia, two tumors received radiation and VLP, and three tumors received only mNP hyperthermia.

Dynamic EPR Oximetry of Changes in Intracerebral Oxygen Tension During Induced Thromboembolism.

Cerebral tissue oxygenation (oxygen tension, pO) is a critical parameter that is closely linked to brain metabolism, function, and pathophysiology. In this work, we have used electron paramagnetic resonance oximetry with a deep-tissue multi-site oxygen-sensing probe, called implantable resonator, to monitor temporal changes in cerebral pO simultaneously at four sites in a rabbit model of ischemic stroke induced by embolic clot. The pO values in healthy brain were not significantly different among the four sites measured over a period of 4 weeks.

Endoscopy after esophagectomy: Safety demonstrated in a porcine model.

Background: Endoscopy is useful in assessing conduit ischemia and anastomotic leaks after esophagectomy but poses a theoretical threat of anastomotic disruption. We used a porcine model to evaluate the safety of endoscopy after esophagectomy.

Methods: We performed esophagectomies in 10 live pigs and performed endoscopy with progressive air insufflation and continuous intraluminal pressure monitoring.

Preliminary Assessment of a Hysteroscopic Fallopian Tube Heat and Biomaterial Technology for Permanent Female Sterilization.

Recent failures in hysteroscopic female sterilization procedures have brought into question the implantation of non-resorbable metal devices into the fallopian tubes due to long-term risks such as migration, fragmentation, and tubal perforation. The goal of this study is to assess whether a porous, biodegradable implant can be deposited into the fallopian tube lumen with or without a local mild heat treatment to generate a safe and permanent fallopian tube occlusion/sterilization event. The technologies investigated included freeze-cast collagen-based scaffolds and magnetic nanoparticle (MNP) based scaffolds.

Toxicity and Pharmacokinetic Profile for Single-Dose Injection of ABY-029: a Fluorescent Anti-EGFR Synthetic Affibody Molecule for Human Use.

Purpose: ABY-029, a synthetic Affibody peptide, Z03115-Cys, labeled with a near-infrared fluorophore, IRDye® 800CW, targeting epidermal growth factor receptor (EGFR) has been produced under good manufacturing practices for a US Food and Drug Administration-approved first-in-use human study during surgical resection of glioma, as well as other tumors. Here, the pharmacology, phototoxicity, receptor activity, and biodistribution studies of ABY-029 were completed in rats, prior to the intended human use.

Procedures: Male and female Sprague Dawley rats were administered a single intravenous dose of varying concentrations (0, 245, 2449, and 24,490 μg/kg corresponding to 10×, 100×, and 1000× an equivalent human microdose level) of ABY-029 and observed for up to 14 days.

Warming barium sulfate improves esophageal leak detection in pig model.

Background: Barium esophagograms have poor sensitivity in detecting leaks. We hypothesized that heating barium would decrease viscosity, facilitate extravasation, and enhance its sensitivity in detecting esophageal leaks.

Methods: We characterized the viscosity of barium at increasing temperatures.

In vitro and in vivo evaluation of SU-8 biocompatibility.

SU-8 negative photoresist is a high tensile strength polymer that has been used for a number of biomedical applications that include cell encapsulation and neuronal probes. Chemically, SU-8 comprises, among other components, an epoxy based monomer and antimony salts, the latter being a potential source of cytotoxicity. We report on the in vitro and in vivo evaluation of SU-8 biocompatibility based on leachates from various solvents, at varying temperatures and pH, and upon subcutaneous implantation of SU-8 substrates in mice.

Intracranial electrical impedance tomography: a method of continuous monitoring in an animal model of head trauma.

Background: Electrical impedance tomography (EIT) is a method that can render continuous graphical cross-sectional images of the brain's electrical properties. Because these properties can be altered by variations in water content, shifts in sodium concentration, bleeding, and mass deformation, EIT has promise as a sensitive instrument for head injury monitoring to improve early recognition of deterioration and to observe the benefits of therapeutic intervention. This study presents a swine model of head injury used to determine the detection capabilities of an inexpensive bedside EIT monitoring system with a novel intracranial pressure (ICP)/EIT electrode combination sensor on induced intraparenchymal mass effect, intraparenchymal hemorrhage, and cessation of brain blood flow.

VEGF and Angiopoietin-1 exert opposing effects on cell junctions by regulating the Rho GEF Syx.

Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoA-specific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous.

The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition.

Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival.

Obesity is mediated by differential aryl hydrocarbon receptor signaling in mice fed a Western diet.

Background: Obesity is a growing worldwide problem with genetic and environmental causes, and it is an underlying basis for many diseases. Studies have shown that the toxicant-activated aryl hydrocarbon receptor (AHR) may disrupt fat metabolism and contribute to obesity. The AHR is a nuclear receptor/transcription factor that is best known for responding to environmental toxicant exposures to induce a battery of xenobiotic-metabolizing genes.

Inherent and benzo[a]pyrene-induced differential aryl hydrocarbon receptor signaling greatly affects life span, atherosclerosis, cardiac gene expression, and body and heart growth in mice.

Little is known of the environmental factors that initiate and promote disease. The aryl hydrocarbon receptor (AHR) is a key regulator of xenobiotic metabolism and plays a major role in gene/environment interactions. The AHR has also been demonstrated to carry out critical functions in development and disease.

ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish.

Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish.

The FGF system has a key role in regulating vascular integrity.

The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors.

Syx, a RhoA guanine exchange factor, is essential for angiogenesis in Vivo.

Rho GTPases play an important and versatile role in several biological processes. In this study, we identified the zebrafish ortholog of the mammalian Rho A guanine exchange factor, synectin-binding guanine exchange factor (Syx), and determined its in vivo function in the zebrafish and the mouse. We found that Syx is expressed specifically in the vasculature of these organisms.