Construction of an analysis system on acute renal failure pathogenesis by direct measurement of renal microcirculation haemodynamics

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The purposes of this study are to visualise the transition of disseminated intravascular coagulation(DIC) in the glomerular microcirculation and to evaluate the effects of heparin and an inhibitor of platelet activating factor, CV3988, by measuring blood flow velocity as an index in a rat. To induce DIC, 5mg/kg of lipopolysaccharide(LPS) was administered intravenously to Wistar rats. Glomerular capillary blood flow velocities were measured with our CCD intravital videomicroscope system, which has a spatial resolution of 0.86μm and a time resolution of 33ms.LPS induced DIC resulting in decrease of glomerular capillary blood flow velocities. Pretreatment with heparin before induction of DIC prevented blood flow velocity decrease approximately by 10%. Pretreatment with CV3988 before induction of DIC prevented blood flow velocity decrease by 90%. Pretreatment with heparin and CV3988 completely abolished the blood flow velocity decrease. Sole administration of either heparin or CV3988 without inducing DIC did not cause any blood flow velocity change at all. CV3988 was more effective than heparin for the blood flow velocity decrease. The pretreatment with both CV3988 and heparin was found to prevent progression of DIC from the aspect of blood flow velocity. This combination treatment is expected to be a new treatment against DIC.