Table 1 Animal models of acute lung injury evaluating the effects of treatment with local anticoagulant therapy.

Rh-APC (12.5 μg/h)

mice

Mechanical ventilation

Aeroneb^a

Rh-APC attenuated pulmonary inflammation, improved oxygenation, and prevented endothelial dysfunction.

Rh-APC did not increase pulmonary bleeding.

Maniatis

[32]

Rh-APC (48 μg/kg/h)

sheep

i.v. LPS

Servo Ultra^b

Rh-APC improved oxygenation and increased aerated lung volume; EVLW was unaffected.

Rh-APC did not cause systemic bleeding.

Waerhaug [33]

Rh-APC (2 × 25 or 100 μg) and repeated dosing

mice

i.t. LPS

Aeroneb Pro^a

Rh-APC attenuated pulmonary coagulation and inflammation; Rh-APC improved lung function.

No differences between single and repeated dosing.

Effects on systemic coagulation or systemic bleeding were not reported.

Slofstra

[34]

Rh-APC (4 mg/3 mL)

mice

i.t. LPS

DeVilbiss^c

Rh-APC attenuated pulmonary inflammation, decreased VCAM-1 upregulation and prevented changes in histopathology.

Effects on systemic coagulation or systemic bleeding were not reported.

Kotanidou [35]

Rh-APC (5,000 μg/kg)

Heparin (1,000 U/kg)

Plasma-derived human AT (500 IU/kg)

Danaparoid

(250 E/kg)

Rats

S. pneumoniae pneumonia

Aeroneb Pro^a

All agents attenuated pulmonary coagulation.

Plasma-derived human AT also attenuated pulmonary inflammation, bacterial outgrowth and changes in histopathology.

Only danaparoid affected systemic coagulation. Systemic bleeding was not reported

Hofstra

[36]

Rh-APC (5,000 μg/kg)

Heparin (1,000 U/kg)

Plasma-derived human AT (500 IU/kg)

Danaparoid

(250 E/kg)

Rats

i.v. LPS

Aeroneb Pro^a

All agents attenuated pulmonary coagulation; pulmonary inflammation and histopathology were not affected.

Heparin and danaparoid affected systemic coagulation. Systemic bleeding was not reported

Hofstra

[37]

Heparin (5 μg) i.t.

mice

Legionella

pneumonia

No nebulizer used

Heparin improved survival and decreased pulmonary inflammation, bacterial outgrowth, Legionella adherence and endothelial permeability.

Effects on systemic coagulation or systemic bleeding were not reported.

Ader

[40]

Heparin

(10,000 IU/4 h)

AT (290 IU)

or a combination

sheep

burn and smoke inhalation

Nebulizer not stated

Combination therapy improved hemodynamics and P/F ratio; airway obstruction and wet-to-dry weight decreased.

Systemic clotting time was unaffected. Systemic bleeding was not reported.

Enkhbaater

[38]

Combination therapy of Heparin (10,000 IU/4 h) and plasma-derived human AT i.v. (0.34 mg/kg/h)

sheep

burn and smoke inhalation

Nebulizer not stated

Heparin + plasma-derived human AT improved P/F ratio; central venous pressure, airway obstruction and wet-to-dry weight decreased.

Systemic levels of AT were elevated. Systemic bleeding was not reported.

Enkhbaatar

[39]

Heparin (10,000 IU/4 h)

or

Heparin i.v.

(5,300 U/kg/23 h)

sheep

burn and smoke inhalation + P. aeruginosa pneumonia

Airlife Misty^d

Nebulization of heparin improved hemodynamics and P/F ratio; airway obstruction, wet-to-dry weight and changes in histopathology were decreased.

Systemic clotting time was unaffected with nebulized heparin. Systemic bleeding was not reported.

Murakami

[41]

Heparin

(10,000 IU/4h)

and/or

Lisofylline i.v.

(10 mg/kg/h after bolus 20 mg/kg)

sheep

burn and smoke inhalation

Nebulizer not stated

Combination therapy decreased the need of mechanical ventilation, P(A-a)O₂ and pulmonary shunt fraction; wet-to-dry weight and changes in histopathology were unaffected.

Effects on systemic coagulation and systemic bleeding were not reported.

Tasaki

[42]