Combined anticoagulants ameliorate acute lung injury in sheep after burn and smoke inhalation.

@article{Enkhbaatar2008CombinedAA,
  title={Combined anticoagulants ameliorate acute lung injury in sheep after burn and smoke inhalation.},
  author={Perenlei Enkhbaatar and Aimalohi Esechie and Jianpu Wang and Robert Ashley Cox and Yoshimitsu Y. Nakano and Atsumori Hamahata and Matthias Lange and Lillian D. Traber and Donald S. Prough and David N. Herndon and Daniel Lee Traber},
  journal={Clinical science},
  year={2008},
  volume={114 4},
  pages={
          321-9
        }
}
Burn and smoke inhalation-related multiple organ dysfunction is associated with a severe fall in the plasma concentration of antithrombin. Therefore the aim of the present study was to test the hypothesis that intravenous administration of recombinant human antithrombin in combination with aerosolized heparin will ameliorate acute lung injury in sheep exposed to cutaneous burn and smoke inhalation. Sheep were prepared operatively for study and, 7 days post-surgery, sheep were given a cutaneous… 

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References

SHOWING 1-10 OF 43 REFERENCES

Heparin Nebulization Attenuates Acute Lung Injury in Sepsis Following Smoke Inhalation in Sheep

Histological changes consisting of cellular infiltrates, lung edema, congestion, and cast formation were reduced by heparin, suggesting that nebulized inhaled Heparin is a beneficial therapy for sepsis-induced ALI.

AEROSOLIZED TISSUE PLASMINOGEN INHIBITOR IMPROVES PULMONARY FUNCTION IN SHEEP WITH BURN AND SMOKE INHALATION

Evidence is provided that clearance of airway obstructive cast material is crucial in managing acute respiratory distress syndrome resulting from combined burn and smoke inhalation injury.

Role of anti-L-selectin antibody in burn and smoke inhalation injury in sheep.

Results suggest that the changes in pulmonary transvascular fluid flux result from injury of lung endothelium by polymorphonuclear leukocytes, and L-selectin may be a useful target in the treatment of acute lung injury after burn and smoke inhalation.

Inducible nitric oxide synthase dimerization inhibitor prevents cardiovascular and renal morbidity in sheep with combined burn and smoke inhalation injury.

A major role is identified for iNOS in mediating extrapulmonary comorbidity in a clinically relevant and severe trauma model and the use of highly selective iNos inhibitors as novel treatments in critical care medicine is supported.

The inducible nitric oxide synthase inhibitor BBS-2 prevents acute lung injury in sheep after burn and smoke inhalation injury.

Evidence is provided that iNOS is a key mediator of pulmonary pathology in sheep with ARDS resulting from combined burn and smoke inhalation injury and treatment of injured sheep with BBS-2 attenuated the increases in tracheal blood flow and plasma NOx levels.

Role of nitric oxide in vascular permeability after combined burns and smoke inhalation injury.

The data suggest that NO produced by iNOS plays an important role in the changes in systemic and pulmonary microvascular permeability in combined smoke inhalation/third-degree burn injury, but does not affect the vascular permeability of third-degree-burned tissue in this type of injury.

Role of L-selectin in physiological manifestations after burn and smoke inhalation injury in sheep.

Findings indicate that both leukocyte-dependent and -independent mechanisms are involved in the pathogenesis that occurs after combined injury with burn and smoke inhalation.

Antithrombin III concentrate in the acute phase of thermal injury.

Airway obstruction in sheep with burn and smoke inhalation injuries.

Results suggest that strategies to remove or decrease formation of upper airway obstructive material may reduce its deposition into small airways and parenchyma and may improve respiratory function in victims of smoke inhalation injury.

High-Dose Antithrombin III in Severe Sepsis: A Randomized Controlled Trial

High-dose antithrombin III therapy had no effect on 28-day all-cause mortality in adult patients with severe sepsis and septic shock when administered within 6 hours after the onset and was associated with an increased risk of hemorrhage when administered with heparin.