Acute effects of complete blood exchange with ultra-purified hemoglobin solution or hydroxyethyl starch on liver and kidney in the animal model

Abstract

The present animal study investigates the influence of an acute and almost complete isovolaemic haemodilution with a new ultrapurified polymerized bovine haemoglobin (UPBH) on hepatic and renal function and histology in comparison to hydroxyethylstarch (HES). Eighteen anaesthetized dogs underwent progressive isovolaemic haemodilution with either HES (group 1) or UPBH (group 2) to haematocrit target levels of 15, 10 and < 5%. Haemodynamics, arterial and mixed-venous blood gases and blood chemistry were determined at each measurepoint. With a haematocrit value < 5%, biopsies were taken from the liver and kidneys and prepared for light and electron microscopic analysis. One dog without haemodilution figured as control animal. Statistical analysis was performed using ANOVA, with p < 0.05 considered significant. In group 1, the cardiac output was increased in parallel to a decreasing vascular resistance, while in group 2 haemodynamic parameters remained unchanged. In group 1, avDO2 and final DO2 and VO2 were decreased. In contrast, avDO2 and oxygen extraction ratio were increased, while VO2 remained stable under decreasing DO2 in group 2. In both groups, coagulation values and blood chemistry showed dilution dependent changes. Colloid osmotic pressure and plasma viscosity were increased in both groups but COP was higher in group 1 compared to group 2. A lower urine output in comparison to group 1 and a maximal concentration of 0.27 g/dl of free haemoglobin in urine were seen in group 2. Liver biopsies showed no severe histological changes in both groups. Renal histology revealed severe alterations of proximal tubules after haemodilution with HES. In contrast, no histological indications for acute toxic or ischaemic lesions in the kidneys were seen after UPBH treatment. The high degree of purification and polymerization of bovine haemoglobin associated with adequate tissue oxygenation by increased oxygen extraction resulted in normal histological and functional findings after acute and almost complete blood exchange with UPBH. In contrast, HES-treated animals showed severe histological changes of renal tubuli caused by isovolaemic anaemia.