Effect of platelet-activating factor antagonist L-691,880 on low-flow ischemia-reperfusion injury of the large colon in horses.

The study investigates the impact of the platelet-activating factor antagonist L-691,880 on low-flow ischemia-reperfusion injury in the large colon of horses, and found that it did not exhibit any protective effects or adverse drug-induced effects to the colonic mucosa during the process.

Study Design

• The research involved 12 adult horses that were anesthetized and whose large colons were externalized and instrumented through a surgery known as ventral median celiotomy.
• The colonic arterial blood flow was reduced to 20% of the original baseline and remained that way for 3 hours. After this, the blood flow was restored and the colon was reperfused for another 3 hours.
• Two groups were created for the study. Group 1 was administered an intravenous solution of 10 mL/kg 0.9% NaCl, and Group 2 was administered an intravenous solution of 5 mg/kg PAF antagonist L-691,880 in 0.9% NaCl, half an hour before reperfusion.

Data Collection

• The researchers monitored and recorded hemodynamic variables at 30-minute intervals throughout the study.
• Systemic arterial and colonic venous blood were collected for measurements such as blood gas tensions, oximetry analyses, packed cell volume, and total plasma protein concentrations.
• In addition, researchers measured lactate, 6-keto prostaglandin F1 alpha (6-kPG), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2) concentrations in the colonic venous blood.

Results

• No significant differences were found between the two groups in any of the hemodynamic or metabolic variables monitored.
• Colonic venous pH decreased and lactate concentration increased during ischemia but returned to baseline values during reperfusion.
• Colonic venous 6-kPG was significantly increased at 2 hours and remained increased through 6 hours in all the horses, irrespective of the group.
• Group 2 showed a significantly higher colonic venous PGE2 concentration compared to group 1 throughout the study.
• There were significant increases in colonic venous TXB2 concentration above baseline value during the first hour of reperfusion, but there was no difference between the two groups.
• Low-flow I-R caused significant damage to the colonic mucosa, shown by necrosis, hemorrhage, edema, and neutrophil infiltration. However, there were no observable differences in these aspects between the horses treated with PAF antagonist and those that were not.

Conclusion

• The use of the PAF antagonist L-691,880 demonstrated no visible protective effect on the colonic mucosa linked to low-flow I-R.
• There were also no observed harmful effects of the drug on hemodynamic and metabolic variables or colonic mucosal injury.