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Summary. Limited normovolemic hemodilution has been performed in splenectemized dogs during pentobarbital anesthesia and controlled ventilation. The hematoerit has been decreased by exchanging arterial blood against dextran 60 until 200/0 was reached. Cardiac output, myocardial contractility, local muscle blood flow and local tissue P02 were investigated in relation to progressive decrease in red cell concentration. Limited normovolemic hemodilution was associated with a significant increase of total and local blood flow; local tissue hypoxia did not develop despite the decrease in oxygen capacity of the blood as proved by the measurements of spatial P02 in liver, kidney, pancreas, small intestine and skeletal muscle. It is concluded that flow improvement in limited normovolemic hemodilution is the key mechanism in maintaining the oxygen supply to the tissues, a fact which favors the concept of normovolemic hemodilution as a therapeutic tool in microcirculatory disorders.Key words: Local tissue POz --Hemodilution --Dextran --Myocardial contractility.L i m i t e d normovolemic hemodilution as induced b y colloidal solutions has been recognized as a causative a p p r o a c h to the impaired microcirculation m a i n l y d e t e r m i n e d b y alterations of the flow properties of blood. N u m e r o u s experiments have shown t h a t the acute reduction of the whole blood viscosity b y dilution will increase the cardiac o u t p u t and the t o t a l organ flow rate [5,20,23,25]. More recently it has been p r o v e d t h a t the increase in cardiac o u t p u t is followed b y an increase in nutritional flow too as suggested from findings obtained in skeletal muscle [19,26]. Since the linear fall of the oxygen c a p a c i t y is associated * Dedicated to Prof. Dr. Dr. R. Zenker on his 70th anniversary. ** Supported in part by grant from Landesamt fiir Forschung of NordrheinWestfalen.Abbreviations. CO = cardiac output, hot = hematocrit, HR = heart rate, M'BF = skeletal muscle blood flow, MCI = myocardial contractility index, RAP = right atrial pressure.

The influence of different environmental oxygen concentrations on vascularization was studied in the yolk sac blood vessel system of chick embryos. The eggs were incubated at normoxic (20.9% oxygen, n = 29), hypoxic (10% oxygen, n = 36) or hyperoxic (100% oxygen, n = 26) conditions and evaluated on day 4 of incubation. In vivo photographs were taken of the vascularized part of the yolk sac membrane (area vasculosa). Prints of a given enlargement were evaluated by histometrical methods to measure the extension of the area vasculosa, the density and the total area of blood vessels. Hypoxia induced an increase in vascular density, in area occupied by blood vessels (44.4%, normoxia = 40.6%) and an enlargement of the area vasculosa (441 ± 78.6 mm2, normoxia = 380 ± 68.7 mm2). Hyperoxia also induced an increase in vascular density and in the area occupied by blood vessels (45.9%), but a decline in the extension of the vascularized area (287 ± 48.8 mm2). Thus the total number of blood vesels as well as the total exchange surface decrease in hyperoxia. Our results indicate that in the area vasculosa of the early chick embryo hypoxia possibly causes an upregulation of vascular growth factors. From the present results it cannot be decided whether vasculogenesis or angiogenesis is stimulated.

To investigate the relationship between hypoxia, neovascularisation and tumour cell spread, experiments on the area vasculosa of the early chick embryo under different oxygen concentrations were performed in vivo. Human glioblastoma cells (U-138MG) were inoculated onto the area vasculosa and the fertilised eggs were incubated under conditions of normoxia or hypoxia. For evaluation, we performed in vivo video-microscopy of the area vasculosa and determination of microvessel density (MVD), as well as a histological examination of the fixed specimen. Under hypoxia, MVD was significantly increased compared to normoxic conditions. Only under hypoxic conditions was tumour cell spread found outside the main tumour mass and within the vessels, at times followed by the subsequent development of secondary tumour cell bulks on the area vasculosa. These data lead to the conclusion that hypoxia can stimulate tumour cell migration in this in vivo model.