Effects Of Acute/chronic Hypoxia On The Rheologic Properties Of Leukocytes In Rats

Leukocytes have very important roles for tissues on defense against pathogen invasion and pathological impairment, but their excess aggregation in tissues and activation could make danger to tissue. Available data have shown that leukocyte activation probably plays an important role in hemorheological disturbance s affecting blood viscosity, because it is associated with the production of leukocyte secretory products (proteolytic enzymes, free radicals, cytokines) which can alter the red cells and make them more aggregable and more rigid. Meanwhile, the rheological properties of leukocyte have important effects on microcirculation perfusion, the deformability of leukocyte decreased or adhesive activity increased. These can directly occlude microvessel and make flow resistance increase. Hypoxia is a complicated pathophysiological process, which can damage immune system. However, relatively little is known about the change of physiological functions of leukocytes inducing by hypoxia. So, the present work focused on the effects of acute/chronic hypoxia on the rheological properties of leukocytes in rats in terms of cellular rheology, in an attempt to deeply understand the pathophysiological significance of leukocytes in the process of hypoxic impairment or acclimatization.Firstly, it was found that the deformability index of erythrocytes in rats decreased in acute hypoxia, but other hemorheological parameters such as whole blood viscosity or reduction viscosity didn't changed obviously. In chronic hypoxia. whole viscosity, reduction viscosity, concentration of hemoglobin and hematocrit were increased significantly, it showed that a significant relation existed between the rheological properties of erythrocyteand blood viscosity. Further, in the pathophysiological analysis it was found that hypoxia might cause marked leukocyte infiltration into lung and brain. That the morphological changes in the lung in acute hypoxia were more evident and more serious than those in chronic hypoxia was found too.The following experiments were designed to extend our understand of the leukocyte emigration response to hypoxia. Specially, we want to determine the mechanics if the response to hypoxia involves the physiological function of leukocyte changed. We founded the microcirculation experiment systems on mesentery and cerebral pia mater in rats and studied the effect of acute/chronic hypoxia on the rheological properties of leukocytes on mesentery and cerebral pia mater microcirculation. Furthermore, the expression of CD 18 on the polymorphonuclear neutrophil was analyzed by flow cytometer. The effects of acute/chronic hypoxia on the viscoelasticity, chemotaxis and fluidity of leukocytes in rats were analyzed by micropipette aspiration techniques and fluorescence polarization techniques. The main results were as follows:1. The rheological properties of leukocytes in the microcirculation of mesentery and cerebral pia mater in rats were changed obviously in acute hypoxia, such as the rolling velocity slowed, the number of rolling leukocytes and adherence on endothelium increased, and TLECT obviously extended than those of the control group. These change of rheological properties were rather weak in chronic hypoxia2. Compared with the control, the expression of CD 18 of PMN was significantly increased in acute hypoxia, but obviously weakened in chronic hypoxia. This might be related to the change of adhesive ability of leukocyte in acute/chronic hypoxia.3. During acute hypoxia produced by a reduction both in inspired PC>2, 5%O2/95%N2 and 10%O2/90%N2, the speed of leukocyte adhered on the endothelium was faster in the former than that in the latter. This suggested thatleukocyte and endothelium interaction had close relevance to the degree of hypoxia.4. In acute hypoxia and chronic hypoxia, the rigidity of leukocytes increased significantly, and passive deformability decreased in comparing with those in the control group.5. In acute hypoxia and chronic hypoxia, the length of pseudopod of...