Early treatment with lexipafant, a platelet-activating factor-receptor antagonist, is not sufficient to prevent pulmonary endothelial damage after intestinal ischaemia and reperfusion in rats.

Abstract

BACKGROUND:

Intestinal ischaemia-reperfusion can lead to pulmonary injury characterised by increased macromolecular leakage and leukocyte sequestration. Important mediators of ischaemia-reperfusion-associated injury include polymorphonuclear granulocytes and platelet-activating factor.

AIM:

To investigate the potential therapeutic inhibition of platelet-activating factor in intestinal ischaemia-reperfusion associated pulmonary injury, by use of a potent platelet-activating factor-receptor antagonist, lexipafant.

METHODS:

Rats were subjected to 30 minutes of intestinal ischaemia followed by 3 or 12 hours reperfusion. Lexipafant or saline was given intraperitoneally after 30 minutes reperfusion.

RESULTS:

Increased leakage of radiolabelled human serum albumin was found in the lungs after intestinal ischaemia followed by 3 or 12 hours reperfusion. Administration of lexipafant did not significantly prevent the increased leakage. Pulmonary myeloperoxidase content increased after intestinal ischaemia-reperfusion, indicating polymorphonuclear granulocyte sequestration through the pulmonary endothelium. The increase in interleukin-1beta seen after 3 hours reperfusion was partly reversed by lexipafant.

CONCLUSIONS:

Pulmonary injury occurred following intestinal ischaemia-reperfusion, characterised by increased leakage of radiolabelled albumin over the endothelial barrier; correlating with increased pulmonary myeloperoxidase-content, implying involvement of polymorphonuclear granulocytes in the pathogenesis of remote organ injury after intestinal ischaemia-reperfusion. Lexipafant did not significantly decrease severity of pulmonary damage.

• Authors: A Börjesson, X Wang, Z Sun, M Inghammar, L Truedsson, R Andersson
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 34 Issue 3 Pg. 190-6 (Mar 2002) ISSN: 1590-8658 [Print] Netherlands
• PMID: 11990391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Imidazoles
• Interleukin-1
• Platelet Activating Factor
• Peroxidase
• Leucine
• lexipafant

Topics

• Animals
• Endothelium, Vascular (drug effects, pathology)
• Imidazoles (pharmacology, therapeutic use)
• Interleukin-1 (blood)
• Leucine (analogs & derivatives, pharmacology, therapeutic use)
• Lung (enzymology)
• Male
• Peroxidase (metabolism)
• Platelet Activating Factor (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, pathology)
• Treatment Failure