Safety of the injectable expanding biopolymer foam for non-compressible truncal bleeding in swine.

Background: A novel hydrophobically modified chitosan (hm-chitosan) polymer has been previously shown to improve survival in a non-compressible intra-abdominal bleeding model in swine. We performed a 28-day survival study to evaluate the safety of the hm-chitosan polymer in swine.

Methods: Female Yorkshire swine (40-50 kg) were used.

Chitosan-based lifefoam improves survival in lethal noncompressible abdominal bleeding in swine.

Background: In military combat settings, noncompressible closed cavity exsanguination is the leading cause of potentially survivable deaths, with no effective treatment available at point of injury. The aim of this study was to assess whether an expanding foam based on hydrophobically modified chitosan (hm-chitosan) may be used as a locally injectable hemostatic agent for the treatment of noncompressible bleeding in a swine model.

Methods: A closed-cavity, grade V hepato-portal injury was created in all animals resulting in massive noncoagulopathic, noncompressible bleeding.

Heparin reduces overcirculation-induced pulmonary artery remodeling through p38 MAPK in piglet.

Background: Artery remodeling is the principal change of pulmonary artery hypertension. Heparin has been shown to inhibit vascular smooth muscle cell proliferation. We hypothesized that heparin may modulate vascular remodeling in pulmonary artery hypertension, and explored the mechanism.

Efficacy of a prehospital self-expanding polyurethane foam for noncompressible hemorrhage under extreme operational conditions.

Background: Noncompressible abdominal hemorrhage is a significant cause of battlefield and civilian mortality. We developed a self-expanding polyurethane foam intended to provide temporary hemorrhage control and enable evacuation to a definitive surgical capability, for casualties who would otherwise die. We hypothesized that foam treatment would be efficacious over a wide range of out-of-hospital operational conditions.

Diagnosis and deployment of a self-expanding foam for abdominal exsanguination: Translational questions for human use.

Background: We have previously described the hemostatic efficacy of a self-expanding polyurethane foam in lethal venous and arterial hemorrhage models. A number of critical translational questions remain, including prehospital diagnosis of hemorrhage, use with diaphragmatic injury, effects on spontaneous respiration, the role of omentum, and presence of a laparotomy on foam properties.

Methods: In Experiment 1, diagnostic blood aspiration was attempted through a Veress needle before foam deployment during exsanguination (n = 53).

Self-expanding foam for prehospital treatment of intra-abdominal hemorrhage: 28-day survival and safety.

Background: Intracavitary noncompressible hemorrhage remains a significant cause of preventable death on the battlefield and in the homeland. We previously demonstrated the hemostatic efficacy of an in situ self-expanding poly(urea)urethane foam in a severe, closed-cavity, hepatoportal exsanguination model in swine. We hypothesized that treatment with, and subsequent explantation of, foam would not adversely impact 28-day survival in swine.

Self-expanding foam improves survival following a lethal, exsanguinating iliac artery injury.

Background: Noncompressible abdominal bleeding is a significant cause of preventable death on the battlefield and in the civilian setting, with no effective therapies available at point of injury. We previously reported that a self-expanding polyurethane foam significantly improved survival in a lethal hepatoportal injury model of massive venous hemorrhage. In this study, we hypothesized that foam treatment could improve survival in a lethal iliac artery injury model in noncoagulopathic swine.

Self-expanding foam for prehospital treatment of severe intra-abdominal hemorrhage: dose finding study.

Background: Noncompressible abdominal bleeding is a significant cause of preventable death on the battlefield and in the civilian trauma environment, with no effective therapies available at point of injury. We previously described the development of a percutaneously administered, self-expanding, poly(urea)urethane foam that improved survival in a lethal Grade V hepatic and portal vein injury model in swine. In this study, we hypothesized that survival with foam treatment is dose dependent.

Development of a lethal, closed-abdomen, arterial hemorrhage model in noncoagulopathic swine.

Background: Prehospital treatment for noncompressible abdominal bleeding, particularly due to large vascular injury, represents a significant unmet medical need on the battlefield and in civilian trauma. To date, few large animal models are available to assess new therapeutic interventions and hemostatic agents for prehospital hemorrhage control.

Methods: We developed a novel, lethal, closed-abdomen injury model in noncoagulopathic swine by strategic placement of a cutting wire around the external iliac artery.

Self-expanding polyurethane polymer improves survival in a model of noncompressible massive abdominal hemorrhage.

Background: Intracavitary noncompressible hemorrhage remains a significant cause of preventable death on the battlefield. Two dynamically mixed and percutaneously injected liquids were engineered to create an in situ self-expanding polymer foam to facilitate hemostasis in massive bleeding. We hypothesized that intraperitoneal injection of the polymer could achieve conformal contact with sites of injury and improve survival in swine with lethal hepatoportal injury.

Development of a lethal, closed-abdomen grade V hepato-portal injury model in non-coagulopathic swine.

Background: Hemorrhage within an intact abdominal cavity remains a leading cause of preventable death on the battlefield. Despite this need, there is no existing closed-cavity animal model to assess new hemostatic agents for the preoperative control of intra-abdominal hemorrhage.

Methods: We developed a novel, lethal liver injury model in non-coagulopathic swine by strategic placement of two wire loops in the medial liver lobes including the hepatic and portal veins.

Low molecular weight (LMW) heparin inhibits injury-induced femoral artery remodeling in mouse via upregulating CD44 expression.

Objective: The mechanism of postangioplasty restenosis remains poorly understood. Low molecular weight (LMW) heparin has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), which is the principal characteristic of restenosis. Studies have shown that LMW heparin could bind to CD44.

Inhibition of HA synthase 3 mRNA expression, with a phosphodiesterase 3 inhibitor, blocks lung injury in a septic ventilated rat model.

Low-molecular-weight hyaluronan produced by hyaluronan synthase 3 (HAS3) has been shown to play a role in acute lung injury secondary to high-tidal-volume ventilation. Phosphodiesterase 3 inhibitors have been shown to decrease HAS3 expression. We hypothesized that low-molecular-weight hyaluronan (LMW HA) produced by HAS3 mediates LPS-induced lung injury in the mechanically ventilated rat and that milrinone (MIL), by blocking HAS3 mRNA expression, would prevent the injury.

The role of phosphodiesterase 3 in endotoxin-induced acute kidney injury.

Background: Acute kidney injury frequently accompanies sepsis. Endotoxin is known to reduce tissue levels of cAMP and low levels of cAMP have been associated with renal injury. We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP and that amrinone an inhibitor of PDE3 would prevent the renal injury.