Korean J Anesthesiol.  2001 Nov;41(5):608-619. 10.4097/kjae.2001.41.5.608.

Effects of Aprotinin on Acute Lung Injury by Endotoxin in Rabbits

• Sim JY
• Choi IC
• Choi SK
• Cho IH
• Ko H

• KMID: 2031917
• DOI: http://doi.org/10.4097/kjae.2001.41.5.608

Abstract

BACKGROUND: Aprotinin, a serine protease inhibitor, has an anti-inflammatory and hemostatic effect and has been used to reduce perioperative blood loss and lung injury after cardiopulmonary bypass in cardiac surgery. Acute respiratory distress syndrome (ARDS), which results in clinical manifestations due to non-cardiogenic permeability edema is a fatal condition associated with a mortality rate of 50 to 80%. The purpose of this study was to evaluate the effects of aprotinin on acute lung injury induced by bacterial endotoxin in rabbits.
METHODS
Nineteen rabbits were anesthetized with intravenous xylazine, Ketamine and vecuronium and ventilated with a Harvard apparatus maintaining normocapnea. In 7 rabbits, 2 mg/Kg of lipopolysaccharide from E. coli was infused intravenously for 30 min (Toxin group) and in another 7 rabbits aprotonin loading with 200,000 KIU/Kg followed by a continuous infusion of 50,000 KIU/Kg/hr was performed 30 min before the endotoxin infusion throughout the experiment (Aprotinin group). At 1, 2, 3, and 4 hours after endotoxin infusion, arterial blood gas, blood cell count, prothrombin time, activated partial thromboplastin time, fibrinogen, and hemodynamic profiles were checKed. At four hours, the animals were dissected at which time the lungs were divided into three regions for wet/dry weight ratio (WW/DW), myeloperoxidase activity and microscopic examination.
RESULTS
In the Aprotinin group, pulmonary vascular resistance, arterial oxygen partial pressure and coagulation function were well preserved compared with the Toxin group. Furthermore, lung WW/DW, myeloperoxidase activity, and inflammatory responses also increased less in the Aprotinin group.
CONCLUSIONS
The results of the current data showed that aprotinin has prophylactic effects against acute lung injury and coagulation impairment induced by bacterial endotoxin in rabbits.

Keyword

Bacteria: endotoxin; Lung: acute lung injury; Pharmacology: aprotinin

MeSH Terms

Acute Lung Injury*
Animals
Aprotinin*
Blood Cell Count
Cardiopulmonary Bypass
Edema
Fibrinogen
Hemodynamics
Ketamine
Lung
Lung Injury
Mortality
Oxygen
Partial Pressure
Partial Thromboplastin Time
Permeability
Peroxidase
Prothrombin Time
Rabbits*
Respiratory Distress Syndrome, Adult
Serine Proteases
Thoracic Surgery
Vascular Resistance
Vecuronium Bromide
Xylazine
Aprotinin
Fibrinogen
Ketamine
Oxygen
Peroxidase
Serine Proteases
Vecuronium Bromide
Xylazine