Flunixin meglumine attenuation of endotoxin-induced damage to the cardiopulmonary vascular endothelium of the pony.
Abstract: Endotoxic shock was induced in 5 ponies by intraperitoneal injections of 20, 40, 60, 80, and 80 micrograms of Escherichia coli endotoxin (LPS)/kg of body weight at 0, 6, 12, 18, and 24 hours, respectively. At 24 hours, the ponies also were given 20 micrograms of LPS/kg via catheter in the left ventricle of the heart. A 2nd group of 4 ponies was given 1.1 mg of flunixin meglumine (FM)/kg, IV, at 6, 12, 18, and 24 hours just before the corresponding LPS injection. Two hours after the 24-hour LPS injection, the ponies in both groups were anesthetized, the lungs were perfused with fixative, and portions of the pulmonary arteries and veins and right and left ventricles were prepared for scanning and transmission electron microscopy. In ponies that were given only LPS, some areas of pulmonary vascular endothelium appeared normal when compared with untreated controls, but other areas had disoriented endothelial cells or had varying amounts of sloughing, which ranged from focal areas of a few cells to large areas of denuded endothelium. Ponies treated with FM before LPS had less severe and less extensive endothelial cell damage. In both groups, leukocytes were attached to areas of the vessel wall; endothelial cell damage was greater in these regions. Administration of FM before LPS administration attenuated the LPS-induced endothelial cell damage.
Publication Date: 1985-03-01 PubMed ID: 3888014
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This study investigates the protective effects of flunixin meglumine (FM) on heart and lung vascular endothelium in ponies subjected to Escherichia coli endotoxin (LPS) induced shock. The results showcase how pretreatment with FM lessened the endothelial cell damage caused by the LPS administration.
Experiment Design
- Endotoxic shock was induced in five ponies through intraperitoneal injections of escalating doses of Escherichia coli endotoxin (LPS) over a span of 24 hours. After the last dose, they were also administered LPS directly into the left ventricle of the heart.
- Another group of four ponies was pretreated with 1.1 mg of FM per kg of body weight through intravenous administration prior to each LPS injection.
- Two hours after the final LPS and FM administrations, the ponies in both groups were anesthetized and parts of their lungs and heart tissues were prepared for microscopic analysis.
Observations and Results
- In ponies administered with only LPS, some parts of the lung vascular endothelium, the innermost lining of the blood vessels, showed signs of disorientation and sloughing.
- Conversely, the ponies that were pretreated with FM demonstrated less severe and extensive endothelial cell damage. The severity and extent of cell damage was assessed through scanning and transmission electron microscopy.
- In both groups, instances of white blood cells attaching to the vessel walls were observed, indicating an active immune response. However, areas with leukocyte attachment tended to exhibit severe endothelial cell damage.
Conclusions
- The results suggest that FM administration prior to LPS exposure can significantly reduce the extent of LPS-induced damage to the endothelial cells in the cardiopulmonary system.
- While this experiment does not provide an in-depth molecular mechanism behind the protective effects of FM, it does open up the possibility of using FM as a preventative strategy against endotoxin-induced cardiopulmonary injuries.
Cite This Article
APA
Turek JJ, Templeton CB, Bottoms GD, Fessler JF.
(1985).
Flunixin meglumine attenuation of endotoxin-induced damage to the cardiopulmonary vascular endothelium of the pony.
Am J Vet Res, 46(3), 591-596.
Publication
Researcher Affiliations
MeSH Terms
- Animals
- Clonixin / analogs & derivatives
- Clonixin / pharmacology
- Clonixin / therapeutic use
- Endocardium / ultrastructure
- Endothelium / drug effects
- Endothelium / ultrastructure
- Escherichia coli
- Female
- Horse Diseases / drug therapy
- Horse Diseases / pathology
- Horses
- Lipopolysaccharides / toxicity
- Male
- Microscopy, Electron
- Microscopy, Electron, Scanning
- Nicotinic Acids / therapeutic use
- Pulmonary Artery / ultrastructure
- Pulmonary Veins / ultrastructure
- Shock, Septic / drug therapy
- Shock, Septic / pathology
- Shock, Septic / veterinary
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