Therapeutic aspects of white blood cell rheology in severe ischaemia of the leg.

In order to investigate the involvement of white blood cells (WBC) in ischaemia, we have used micropore filtration techniques to measure the flow properties of cells from patients with severe leg ischaemia, before and after therapy (amputation or pharmacological). Compared to age-matched controls, WBC from patients had impaired ability to flow through 8 microns and 5 microns pore filters. This applied to fractionated granulocytes and mononuclear cells, as well as to unfractionated mixed WBC. WBC from blood drawn from the ischaemic leg had worse filterability than those from arm blood of the same patients. Judging from WBC morphology, the percentage of active WBC was higher in samples drawn from ischaemic patients compared to controls. After amputation of the ischaemic leg, significant improvement was observed, so that the WBC were no longer significantly different from controls. The flow abnormalities may reflect activation of WBC by factors released in the ischaemic tissue. A cycle of WBC trapping, activation, tissue damage and further activation and trapping could contribute to the worsening of tissue ischaemia. Pharmacological intervention in this degenerative cycle might be possible, and our preliminary data show that Trental infusion (600 mg over 6 hours) improves the filterability of granulocytes from severely ischaemic patients.