Treatment of Swine Closed Head Injury with Perfluorocarbon NVX-428.

Pre-hospital treatment of traumatic brain injury (TBI) with co-existing polytrauma is complicated by requirements for intravenous fluid volume vs. hypotensive resuscitation. A low volume, small particle-size-oxygen-carrier perfluorocarbon emulsion NVX-428 (dodecafluoropentane emulsion; 2% / could improve brain tissue with minimal additional fluid volume.

Blood transfusions, blood storage, and correlation with elevated pulmonary arterial pressures.

Background: The aim of this study was to determine if transfusion with RBCs is associated with a rise in mean pulmonary artery pressure (MPAP) and whether such a rise is influenced by the duration of RBC storage.

Study Design And Methods: A retrospective chart review of intensive care unit patients with pulmonary artery catheters was conducted at two military medical centers.

Results: RBC transfusion is associated with a sustained (≥4 hours) statistically significant 2- to 3-mm Hg rise in MPAP relative to both pretransfusion levels (p < 0.

Hypobaria during long-range flight resulted in significantly increased histopathological evidence of lung and brain damage in a swine model.

Background: Aeromedical evacuation to definitive care is standard in current military conflicts. However, there is minimal knowledge on the effects of hypobaria (HYPO) on either the flight crew or patients. The effects of HYPO were investigated using healthy swine.

Brain oxygenation with a non-vasoactive perfluorocarbon emulsion in a rat model of traumatic brain injury.

Objective: The aim of this study was to assess, in two experiments, the safety and efficacy of the PFC emulsion Oxycyte as an oxygen therapeutic for TBI to test the hypothesis that early administration of this oxygen-carrying fluid post-TBI would improve brain tissue oxygenation (P O ).

Methods: The first experiment assessed the effects of Oxycyte on cerebral vasoactivity in healthy, uninjured rats using intravital microscopy. The second experiment investigated the effect of Oxycyte on cerebral P O using the PQM in TBI model.

Perfluorocarbon in Delayed Recompression with a Mixed Gender Swine Model of Decompression Sickness.

Introduction: Perfluorocarbons (PFC) are fluorinated hydrocarbons that dissolve gases to a much greater degree than plasma and hold promise in treating decompression sickness (DCS). The efficacy of PFC in a mixed gender model of DCS and safety in recompression therapy has not been previously explored.

Methods: Swine (25 kg; N = 104; 51 male and 53 female) were randomized into normal saline solution (NSS) or PFC emulsion treatment groups and subjected to compression on air in a hyperbaric chamber at 200 fsw for 31 min.

Cerebral Microvascular and Systemic Effects Following Intravenous Administration of the Perfluorocarbon Emulsion Perftoran.

Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model.

The Emulsified PFC Oxycyte Improved Oxygen Content and Lung Injury Score in a Swine Model of Oleic Acid Lung Injury (OALI).

Purpose: Perfluorocarbons (PFCs) can transport 50 times more oxygen than human plasma. Their properties may be advantageous in preservation of tissue viability in oxygen-deprived states, such as in acute lung injury. We hypothesized that an intravenous dose of the PFC emulsion Oxycyte would improve tissue oxygenation and thereby mitigate the effects of acute lung injury.

Sanguinate's effect on pial arterioles in healthy rats and cerebral oxygen tension after controlled cortical impact.

Sanguinate, a polyethylene glycol-conjugated carboxyhemoglobin, was investigated for cerebral vasoactivity in healthy male Sprague-Dawley rats (Study 1) and for its ability to increase brain tissue oxygen pressure (PbtO2) after controlled cortical impact (CCI) - traumatic brain injury (TBI) (Study 2). In both studies ketamine-acepromazine anesthetized rats were ventilated with 40% O2. In Study 1, a cranial window was used to measure the diameters of medium - (50-100μm) and small-sized (<50μm) pial arterioles before and after four serial infusions of Sanguinate (8mL/kg/h, cumulative 16mL/kg IV), volume-matched Hextend, or normal saline.

Infusion of solutions of pre-irradiated components in rats.

Introduction: The objective of this study was to conduct a 14-day toxicology assessment for intravenous solutions prepared from irradiated resuscitation fluid components and sterile water.

Methods: Healthy Sprague Dawley rats (7-10/group) were instrumented and randomized to receive one of the following Field IntraVenous Resuscitation (FIVR) or commercial fluids; Normal Saline (NS), Lactated Ringer's, 5% Dextrose in NS. Daily clinical observation, chemistry and hematology on days 1,7,14, and urinalysis on day 14 were evaluated for equivalence using a two sample t-test (p<0.

Brain hypoxia is exacerbated in hypobaria during aeromedical evacuation in swine with traumatic brain injury.

Background: There is inadequate information on the physiologic effects of aeromedical evacuation on wounded war fighters with traumatic brain injury (TBI). At altitudes of 8,000 ft, the inspired oxygen is lower than standard sea level values. In troops experiencing TBI, this reduced oxygen may worsen or cause secondary brain injury.

Endovascular Cooling Method for Hypothermia in Injured Swine.

We evaluated an endovascular cooling method to modulate core temperature in trauma swine models with and without fluid support. Anesthetized swine (N = 80) were uninjured (SHAM) or injured through a bone fracture plus soft tissue injury or an uncontrolled hemorrhage and then subdivided to target body temperatures of 38°C (normothermia) or 33°C (hypothermia) by using a Thermogard endovascular cooling device (Zoll Medical). Temperature regulation began simultaneously at onset of injury (T0).

Perfluorocarbon NVX-108 increased cerebral oxygen tension after traumatic brain injury in rats.

Background: Hypoxia is a critical secondary injury mechanism in traumatic brain injury (TBI), and early intervention to alleviate post-TBI hypoxia may be beneficial. NVX-108, a dodecafluoropentane perfluorocarbon, was screened for its ability to increase brain tissue oxygen tension (PbtO2) when administered soon after TBI.

Methods: Ketamine-acepromazine anesthetized rats ventilated with 40% oxygen underwent moderate controlled cortical impact (CCI)-TBI at time 0 (T0).

Advances in Intracranial Pressure Monitoring and Its Significance in Managing Traumatic Brain Injury.

Intracranial pressure (ICP) measurements are essential in evaluation and treatment of neurological disorders such as subarachnoid and intracerebral hemorrhage, ischemic stroke, hydrocephalus, meningitis/encephalitis, and traumatic brain injury (TBI). The techniques of ICP monitoring have evolved from invasive to non-invasive-with both limitations and advantages. Some limitations of the invasive methods include short-term monitoring, risk of infection, restricted mobility of the subject, etc.

The effect of the perfluorocarbon emulsion Oxycyte on platelet count and function in the treatment of decompression sickness in a swine model.

Decompression from elevated ambient pressure is associated with platelet activation and decreased platelet counts. Standard treatment for decompression sickness (DCS) is hyperbaric oxygen therapy. Intravenous perfluorocarbon (PFC) emulsion is a nonrecompressive therapy being examined that improves mortality in animal models of DCS.

Cerebral Vasoactivity and Oxygenation with Oxygen Carrier M101 in Rats.

The severity of traumatic brain injury (TBI) may be reduced if oxygen can be rapidly provided to the injured brain. This study evaluated if the oxygen-carrier M101 causes vasoconstricton of pial vasculature in healthy rats (Experiment 1) and if M101 improves brain tissue oxygen (PbtO) in rats with controlled cortical impact (CCI)-TBI (Experiment 2). M101 (12.

Effects of the Oxygen-Carrying Solution OxyVita C on the Cerebral Microcirculation and Systemic Blood Pressures in Healthy Rats.

The use of hemoglobin-based oxygen carriers (HBOC) as oxygen delivering therapies during hypoxic states has been hindered by vasoconstrictive side effects caused by depletion of nitric oxide (NO). OxyVita C is a promising oxygen-carrying solution that consists of a zero-linked hemoglobin polymer with a high molecular weight (~17 MDa). The large molecular weight is believed to prevent extravasation and limit NO scavenging and vasoconstriction.

Cardiovascular parameters in a mixed-sex swine study of severe decompression sickness treated with the emulsified perfluorocarbon Oxycyte.

Intravenous perfluorocarbons (PFC) have reduced the effects of decompression sickness (DCS) and improved mortality rates in animal models. However, concerns for the physiological effects of DCS combined with PFC therapy have not been examined in a balanced mixed-sex population. Thirty-two (16 male, 16 female) instrumented and sedated juvenile Yorkshire swine were exposed to 200 feet of seawater (fsw) for 31 min of hyperbaric air.

Effects of perfluorocarbon dodecafluoropentane (NVX-108) on cerebral microvasculature in the healthy rat.

NVX-108, a dodecafluoropentane-based perfluorocarbon (PFC) emulsion, has therapeutic potential as an oxygen- carrying fluid for emergency medical treatment for traumatic brain injury (TBI) and hemorrhagic shock. Potential cerebral vasoactive properties were assessed by directly measuring pial arteriolar vessel diameters before and after a 30 minute intravenous (IV) infusion of 1.0 ml/kg (high dose [H]) or 0.

Use of recombinant factor VIIa (rFVIIa) as pre-hospital treatment in a swine model of fluid percussion traumatic brain injury.

Context: Recombinant factor VIIa (rFVIIa) has been used as an adjunctive therapy for acute post-traumatic hemorrhage and reversal of iatrogenic coagulopathy in trauma patients in the hospital setting. However, investigations regarding its potential use in pre-hospital management of traumatic brain injury (TBI) have not been conducted extensively.

Aims: In the present study, we investigated the physiology, hematology and histology effects of a single pre-hospital bolus injection of rFVIIa compared to current clinical practice of no pre-hospital intervention in a swine model of moderate fluid percussion TBI.

Effects of N-acetyl-L-cysteine and hyaluronic acid on HBOC-201-induced systemic and cerebral vasoconstriction in the rat.

Hemoglobin-based oxygen carrier-201 (HBOC) was developed as a resuscitative fluid but concerns exist over potentially adverse vasoconstriction. This study evaluated whether concurrent IV (intra venous) N-acetyl-L-cysteine (NAC) or hyaluronic acid (HA) would attenuate HBOC-associated vasoconstriction, assessed by systemic blood pressures and cerebral pial microvasculature, when administered to healthy, anesthetized rats. Rats (8-9/group) received a 30 min infusion of 3 ml/kg HBOC, HBOC plus 600 mg/kg NAC (HBOC/NAC), HBOC plus 1.

The intravenous perfluorocarbon emulsion Oxycyte does not increase hyperbaric oxygen-related seizures in a non-sedated swine model.

Purpose: Standard treatment for decompression sickness (DCS) is recompression therapy with hyperbaric oxygen (HBO). Non-recompressive therapies are needed to address mass casualty scenarios such as a disabled submarine rescue or DCS therapy in remote environments. Intravenously delivered perfluorocarbon (PFC) emulsions improve blood oxygen content and decrease mortality in several animal models of DCS.

Effects of top-loading a zero-link bovine hemoglobin, OxyVita, on systemic and microcirculatory variables.

This study was designed to test the effect of top-load infusions of increasing doses of two versions of the novel, high molecular weight hemoglobin-based oxygen carrier, OxyVita and OxyVita C solution ([Hb] = 6 g/dL), on mean arterial pressure (MAP), arteriolar diameter, and tissue oxygenation. Experiments were carried out on 18 anesthetized male Sprague-Dawley rats in which microcirculatory observations were made on the spinotrapezius muscle. Intravenous infusions of four increasing doses of the OxyVita solutions (2, 22, 230, and 780 mg/kg) were made for each group, and a separate group of animals was used for volume control.

Fluid resuscitation of uncontrolled hemorrhage using a hemoglobin-based oxygen carrier: effect of traumatic brain injury.

Animal models of combined traumatic brain injury (TBI) and hemorrhagic shock (HS) suggest a benefit of hemoglobin-based oxygen carrier (HBOC)-based resuscitation, but their use remains controversial, and little is known of the specific effects of TBI and high-pressure (large arterial injury) bleeding on resuscitation. We examine the effect of TBI and aortic tear injury on low-volume HBOC resuscitation in a swine polytrauma model and hypothesize that HBOC-based resuscitation will improve survival in the setting of aortic tear regardless of the presence of TBI. Anesthetized swine subjected to HS with aortic tear with or without fluid percussion TBI underwent equivalent limited resuscitation with HBOC, lactated Ringer's solution, or HBOC + nitroglycerine (vasoattenuated HBOC) and were observed for 6 h.

The emulsified perfluorocarbon Oxycyte improves spinal cord injury in a swine model of decompression sickness.

Study Design: A prospective, animal model for pharmacological intervention of decompression sickness (DCS), including spinal cord (SC) injury.

Background: Signs and symptoms of DCS can include joint pain, skin discoloration, cardiopulmonary congestion and SC injury; severity ranges from trivial to fatal. Non-recompressive therapy for DCS may improve time-to-treatment and therefore impact mortality and morbidity.

Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: an exploratory study in a swine controlled haemorrhage model.

Background: Vasoconstriction is a side effect that may prevent the use of haemoglobin based oxygen carrier (HBOC) as blood substitute. Therefore, we tested the hypothesis that the NO donor, sodium nitroprusside (SNP), would mitigate systemic and pulmonary hypertension associated with HBOC-201 in a simple controlled haemorrhage swine model.

Methods: After 55% estimated blood volume withdrawal through a venous catheter, invasively anesthetized and instrumented animals were resuscitated with three 10 ml/kg infusions of either HBOC-201 or Hextend (HEX) with or without 0.