Effects of repeated endotoxin injections on prostanoids, hemodynamics, endothelial cells, and survival in ponies.
Abstract: The objectives of this study were to determine the pathophysiological effects of increasing amounts of endotoxin administered intraperitoneally (IP) for 24 hr at which time an intravenous (IV) injection of endotoxin was given. The ability of flunixin meglumine (FM), a nonsteroidal antiinflammatory drug with antiprostaglandin activity, to provide protective effects was also determined. Eight ponies were divided into two groups of four ponies each; one group (untreated) received endotoxin only and the other group (treated) received endotoxin while being treated with flunixin. Hemodynamic and serum prostanoid changes were recorded for 26 hr during which time five IP and one IV endotoxin injections were given. Both groups behaved similarly until the intravenous endotoxin injection at 24 hr. At that time, the protective effects of flunixin became apparent by preventing increases in thromboxane and prostacyclin concentrations and by maintaining cardiac output, systemic arterial blood pressure, and blood flow to critical organs. Electron microscopic examination of pulmonary arteries of untreated animals revealed extensive endothelial cell damage while treatment with FM reduced this damage. A parallel study involving survival time in two groups of eight ponies each was also conducted using the same endotoxin and treatment protocol. At the end of 7 days, two of eight untreated ponies survived while six of eight treated ponies survived. It was concluded that FM prevented the release of prostanoids, maintained hemodynamics and blood flow nearer pre-endotoxin values, reduced vascular endothelial cell damage, and improved survival.
Publication Date: 1985-01-01 PubMed ID: 3840414
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The study aimed to investigate the effects of increasing doses of endotoxin on prostanoids, hemodynamics, endothelial cells, and survival in ponies. It also explored the protective influence of flunixin meglumine (FM), an anti-inflammatory drug, against these effects.
Research Design and Methodology
- The research involved eight ponies, which were divided into two groups. One group only received endotoxin injections, while the second was treated with endotoxin and flunixin.
- The scientists administered endotoxin intraperitoneally (within the peritoneal cavity) for 24 hours, after which they gave an intravenous endotoxin injection. At the same time, they monitored the ponies’ hemodynamic alterations and changes in serum prostanoid levels.
- The researchers also conducted a parallel study to investigate the survival time of two separate groups of eight ponies each, following the same endotoxin and treatment protocol.
Findings and Conclusion
- Both groups responded similarly until the delivery of the intravenous endotoxin injection after 24 hours. At this point, the protective power of flunixin became evident, as it prevented increases in prostacyclin and thromboxane concentrations while maintaining the cardiac output, systemic arterial blood pressure, and critical organ blood flow.
- Microscopic examination of the pulmonary arteries from the untreated ponies revealed extensive endothelial cell damage, whereas the group treated with FM showed reduced damage.
- In the survival study, two out of eight untreated ponies survived after seven days, compared to six out of eight in the treated group. This indicates that flunixin can significantly improve survival rates amongst ponies subjected to endotoxin administration.
- The results suggest that flunixin meglumine can effectively prevent the release of prostanoids, stabilize hemodynamics and blood flow, reduce vascular endothelial cell damage, and enhance survival.
In conclusion, this study provides valuable insight into the potential of flunixin meglumine as a protective treatment against the pathophysiological effects of repeated endotoxin administration in ponies.
Cite This Article
APA
Templeton CB, Bottoms GD, Fessler JF, Turek JJ, Boon GD.
(1985).
Effects of repeated endotoxin injections on prostanoids, hemodynamics, endothelial cells, and survival in ponies.
Circ Shock, 16(3), 253-264.
Publication
Researcher Affiliations
MeSH Terms
- 6-Ketoprostaglandin F1 alpha / blood
- Animals
- Arteries / cytology
- Arteries / drug effects
- Blood Pressure / drug effects
- Cardiac Output / drug effects
- Clonixin / analogs & derivatives
- Clonixin / therapeutic use
- Endothelium / drug effects
- Endothelium / ultrastructure
- Endotoxins / administration & dosage
- Endotoxins / pharmacology
- Female
- Gastroenteritis / microbiology
- Gastroenteritis / mortality
- Gastroenteritis / physiopathology
- Hemodynamics / drug effects
- Horse Diseases / mortality
- Horse Diseases / physiopathology
- Horses
- Male
- Meglumine / therapeutic use
- Microscopy, Electron
- Prostaglandins / blood
- Regional Blood Flow / drug effects
- Sepsis / mortality
- Sepsis / physiopathology
- Thromboxane B2 / blood
- Time Factors
Citations
This article has been cited 1 times.- Töns C, Klosterhalfen B, Klinge U, Kirkpatrick CJ, Mittermayer C, Schumpelick V. [Septic shock and multiple organ failure in surgical intensive care. An animal experiment model on the analysis of pulmonary and intestinal dysfunction]. Langenbecks Arch Chir 1993;378(4):217-32.
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