Oxygenation through oral Ox66 in a two-hit rodent model of respiratory distress.

Acute respiratory distress syndrome (ARDS) is a complication of pulmonary disease that produces life-threatening hypoxaemia. Despite ventilation and hyperoxic therapies, undetected hypoxia can manifest in capillary beds leading to multi-organ failure. Ox66™ is an ingestible, solid-state form of oxygen designed to supplement oxygen deficits.

EXCHANGE TRANSFUSION WITH VS -101: A NEW PEGYLATED-HB DESIGNED TO RESTORE PERFUSION AND INCREASE O 2 CARRYING CAPACITY.

Blood products are the current standard for resuscitation of hemorrhagic shock. However, logistical constraints of perishable blood limit availability and prehospital use, meaning alternatives that provide blood-like responses remain an area of active investigation and development. VS-101 is a new PEGylated human hemoglobin-based oxygen carrier that avoids the logistical hurdles of traditional blood transfusion.

Dynamics of PO and VO in resting and contracting rat spinotrapezius muscle.

This study examined changes in interstitial PO, which allowed calculation of VO during periods of rest, muscle contraction and recovery using an rat spinotrapezius muscle preparation. The PO was measured using phosphorescence quenching microscopy and the muscle VO was calculated as the rate of O disappearance during brief periods of muscle compression to stop blood flow with a supra-systolic pressure. The PO and VO measurements were made during "5 s compression and 15 s recovery" (CR) cycles.

Novel transdermal curcumin therapeutic preserves endothelial barrier function in a high-dose LPS rat model.

Sepsis is a devastating complication of infection and injury that, through widespread endothelial dysfunction, can cause perfusion deficits and multi-organ failure. To address the recognised need for therapeutics targetting the endothelial barrier, a topical formulation (CUR; VASCEPTOR™; Vascarta Inc, Summit, NJ) was developed to transdermally deliver bio-active concentrations of curcumin-an anti-inflammatory and nitric oxide promoter. Male, Sprague Dawley rats were treated daily with lipopolysaccharide (LPS, 10 mg/kg, IP) to induce endotoxemia, and topical applications of Vehicle Control (LPS + VC;  = 7) or Curcumin (LPS + CUR;  = 7).

Evaluation of an Injectable, Solid-State, Oxygen-Delivering Compound (Ox66) in a Rodent Model of Pulmonary Dysfunction-Induced Hypoxia.

Introduction: Pulmonary dysfunction (PD) and its associated hypoxia present a complication to the care of many service members and can arise intrinsically via comorbidities or extrinsically by infection or combat-related trauma (burn, smoke inhalation, and traumatic acute lung injury). Current supportive treatments (e.g.

Gavage approach to oxygen supplementation with oxygen therapeutic Ox66™ in a hypoventilation rodent model of respiratory distress.

Acute respiratory distress syndrome (ARDS) features pulmonary dysfunction capable of causing life-threatening hypoxaemia. Ventilation and hyperoxic therapies force oxygen through dysfunctional alveoli but risk exacerbating damage. Ox66™ is an ingestible, solid-state oxygen product designed for oxygen supplementation.

Spike of interstitial PO produced by a twitch in rhythmically contracted muscle.

Oxygen (O ) exchange between capillaries and muscle cells in exercising muscles is of great interest for physiology and kinesiology. However, methodical limitations prevent O measurements on the millisecond scale. To bypass the constraints of quasi-continuous recording, progressive measurements of O partial pressure (PO ) in rhythmically contracting skeletal muscle were compiled to describe the O kinetics surrounding and including a single muscle contraction.

Systemic and microvascular comparison of Lactated Ringer's solution, VIR-HBOC, and alpha-alpha crosslinked haemoglobin-based oxygen carrier in a rat 10% topload model.

Medical support for traumatic haemorrhage is lacking for far-forward combat units. VIR-HBOC (haemoglobin-based oxygen carrier) is a novel biological therapeutic under development as a field-stable resuscitation fluid. HBOCs have a long history of complications, chief among them is vasoconstrictive hypertension, which must be resolved before efficacy testing.

Physiological and microvascular responses to hemoglobin concentration-targeted hemolytic anemia in rats.

Hemolytic anemia (HA) is reduced blood oxygen-carrying capacity resulting from the depletion of red blood cells. Treatment for severe cases involves transfusion to improve oxygen delivery (Do), which carries risk. In humans, a total hemoglobin (tHb) concentration of 8 g/dL is severe, and <7 g/dL indicates transfusion.

Improved Hemodynamic Recovery and 72-Hour Survival Following Low-Volume Resuscitation with a PEGylated Carboxyhemoglobin in a Rat Model of Severe Hemorrhagic Shock.

Introduction: Hemorrhage is a leading cause of death from potentially survivable civilian and military trauma. As projected conflicts move from settings of tactical and logistical supremacy to hyper-dynamic tactical zones against peer and near-peer adversaries, protracted medical evacuation times are expected. Treatment at the point-of-injury is critical.

Microvascular and Systemic Impact of Resuscitation with PEGylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch in a Rat Model of Transient Hemorrhagic Shock.

Background: Hemorrhage is the leading cause of preventable, traumatic death. Currently, prehospital resuscitation fluids provide preload but not oxygen-carrying capacity-a critical blood function that mitigates microvascular ischemia and tissue hypoxia during hemorrhagic shock. Solutions containing polymerized hemoglobin have been associated with vasoactive and hypertensive events.

Microvascular and systemic responses to novel PEGylated carboxyhaemoglobin-based oxygen carrier in a rat model of vaso-occlusive crisis.

Hypoxia drives sickle cell disease (SCD) by inducing sickle cell haemoglobin to polymerize and deform red blood cells (RBC) into the sickle shape. A novel carboxyhaemoglobin-based oxygen carrier (PEG-COHb; PP-007) promotes unsickling in vitro by relieving RBC hypoxia. An in vivo rat model of vaso-occlusive crisis (VOC) capable of accommodating a suite of physiological and microcirculatory measurements was used to compare treatment with PEG-COHb to a non-oxygen carrying control solution (lactated ringer's [LRS]).

Oral ingestion of a novel oxygenating compound, Ox66™, is non-toxic and has the potential to increase oxygenation.

Ox66™ is a novel solid state oxygenating compound. In order to support the use of Ox66™ as a potential oxygenating supplement to injured cells, this study evaluated the safety of Ox66™, its ability to withstand the conditions in the digestive tract, and its potential to increase oxygenation in the mesentery in rats. The toxicity of Ox66™ was evaluated by performing acute (10-day) and chronic (90-day) feeding studies on rats, the stability of the compound in the digestive tract was evaluated via ex vivo simulated digestion and subsequent CFDA viability assay on gut epithelial cells, and its capacity for oxygenation in the mesenteric microcirculation was determined by interstitial fluid pressure (P) O measurements upon injection into the small intestine of rats.

Effects of Sanguinate on Systemic and Microcirculatory Variables in a Model of Prolonged Hemorrhagic Shock.

Background: Hemorrhage and its complications are the leading cause of preventable death from trauma in young adults, especially in remote locations. To address this, deliverable, shelf-stable resuscitants that provide therapeutic benefits throughout the time course of hemorrhagic shock and the progressive ischemic injury it produces are needed. SANGUINATE is a novel bovine PEGylated carboxyhemoglobin-based oxygen carrier, which has desirable oxygen-carrying and oncotic properties as well as a CO moiety to maintain microvascular perfusion.

Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle.

Under physiologic conditions, microvascular oxygen delivery appears to be well matched to oxygen consumption in respiring tissues. We present a technique to measure interstitial oxygen tension (PISFO2) and oxygen consumption (VO2) under steady-state conditions, as well as during the transitions from rest to activity and back. Phosphorescence Quenching Microscopy (PQM) was employed with pneumatic compression cycling to achieve 1 to 10 Hz sampling rates of interstitial PO2 and simultaneous recurrent sampling of VO2 (3/min) in the exteriorized rat spinotrapezius muscle.

Effects of a hemoglobin-based oxygen carrier (HBOC-201) and derivatives with altered oxygen affinity and viscosity on systemic and microcirculatory variables in a top-load rat model.

The effects of a polymerized bovine hemoglobin-based oxygen carrier (HBOC) and two derivatives on arteriolar vasoactivity and tissue oxygen tension were explored by administering HBOC in a dose-response fashion to normovolemic rats. The effect of oxygen affinity (P50) and viscosity was also explored, where the P50 and viscosity of the parent compound (HBOC-201) and its modifications (MP50 and LP50A) were as follows: 40mmHg and 3.0cP (HBOC-20l); 18mmHg and 4.

Muscle contraction increases interstitial nitric oxide as predicted by a new model of local blood flow regulation.

The prevailing metabolic theory of local blood flow regulation suggests the dilatation of arterioles in response to tissue hypoxia via the emission of multiple metabolic vasodilators by parenchymal cells. We have proposed a mechanism of regulation, built from well-known components, which assumes that arterioles are normally dilated in metabolically active tissues, due to the emission of NO by the endothelium of microvessels. Regulation of local blood flow aims at preventing an excessive supply of oxygen (O2) and glucose to the tissue and thus provides an adequate supply, in contrast to the metabolic regulation theory which requires permanent hypoxia to generate the metabolic vasodilators.

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.

The rate of O₂ loss from mesenteric arterioles is not unusually high.

The O(2) disappearance curve (ODC) recorded in an arteriole after the rapid arrest of blood flow reflects the complex interaction among the dissociation of O(2) from hemoglobin, O(2) diffusivity, and rate of respiration in the vascular wall and surrounding tissue. In this study, the analysis of experimental ODCs allowed the estimation of parameters of O(2) transport and O(2) consumption in the microcirculation of the mesentery. We collected ODCs from rapidly arrested blood inside rat mesenteric arterioles using scanning phosphorescence quenching microscopy (PQM).