Leukocyte Filterability in Patients with Various Subtype of Cerebral Infarction and in vitro Effects of FMLP, PAF and PAF Antagonist

Several clinical studies have shown decreased erythrocyte filterability during cerebral ischemia. Concomitantly, leukocytes may become activated, and may release chemical mediators such as leukotrienes and platelet-activating factor (PAF), which act to increase chemotaxis and their adhesiveness, and thus leukocytes may be associated with the pathogenesis of microcirculatory impairment, particularly in the area of ischemic penumbra.In this study, to examine the rheologic behavior of leukocytes in cerebral vascular disease, we measured the leukocyte filterability through a Milipore membrane of leukocyte subpopulations in 34 patients with various subtypes of cerebral infarction (12 atherothrombotic, 17 lacunar, and 5 cardioembolic), who were compared with 13 normal controls, using the St. George's filtrometer. In addition, formyl-methionyl-leucyl-phenylalanine (FMLP) and PAF were added to the leukocyte suspensions, that were separated from heparinized whole blood obtained from healthy volunteers, and the effects on leukocyte filterability were studied. The effect of TCV 309 (PAF antagonist) on leukocyte filtreability was also determined after stimulation of leukocytes with PAF.Leukocyte filterability was reduced in patients with atherothrombotic stroke and lacunar stroke but not in those with cardioembolic stroke compared with controls (p<0.05). There was no significant difference in leukocyte filterability between patients treated with and without antiplatelet agents (aspirin and/or ticlopidine). In vitro study, FMLP and PAF decreased leukocyte filterability, and TCV 309 improved the filterability of leukocytes activated with PAF.Decreased leukocyte filterability in patients with atherothrombotic and lacunar stroke may play a role in the pathophysiology of microcirculatory impairment. An pharmacological improvement of leukocyte filterability may be a new strategy for treating microcirculatory impairment in the penumbra area associated with cerebral ischemia. Further ex vivo studies on this class of compounds appear necessary for clinical application in future.