Iloprost reduces leukocyte adhesion in skeletal muscle venules following ischaemia in a rat model of femorodistal bypass

Abstract

Intraarterial bolus treatment with the prostacyclin analogue iloprost appears to have a prolonged beneficial effect on femorodistal bypass graft flow which extends beyond the duration of its vasodilator properties. The effect of iloprost on the microcirculation rendered ischaemic over the time course of a distal bypass operation was investigated in this study without the use of fluorescent light. Methods: A rat model was designed to allow prolonged direct observation of leukocyte-venular endothelial adhesion in a femorodistal bypass simulation. The extensor digitorum longus (EDL) muscle of 10 rats was subjected to two 30 minute periods of ischaemia by a non-venous occluding tourniquet and to simulate some of the changes of chronic ischaemia the adverse effect of ischaemia was accentuated by indirect electrical stimulation via the lateral popliteal nerve. Results: Intraarterial bolus treatment with iloprost significantly reduced the total numbers of leukocytes observed in EDL venules, and the numbers exhibiting evidence of adhesion by rolling or sticking to venule endothelium compared with saline controls at one hour post ischaemia. Ischaemia induced vasodilatation and reduced shear stress by a similar and significant amount in both groups. Conclusion: Two periods of ischaemia and reperfusion similar to those which occur during bypass grafting resulted in changes in the distal microcirculation consistent with reperfusion injury. Intraarterial bolus treatment with iloprost prevented these leucocyteendothelial changes. It appears iloprost may have a role in reducing leukocyte-induced reperfusion injury in femorodistal bypass surgery.