Systemic and splanchnic hemodynamics of the chronic bile duct-ligated rat were characterized by radioactive microspheres. Conscious and pentobarbital sodium-anesthetized, bile duct-ligated and sham-operated rats had cardiac output and regional organ blood flows determined. The conscious bile duct-ligated rat compared with the sham-operated showed a hyperdynamic circulation with an increased cardiac output (153.3 +/- 9.8 vs. 112.6 +/- 6.0 ml/min, P less than 0.005) and portal tributary blood flow (21.32 +/- 1.43 vs. 12.79 +/- 1.47 ml/min, P less than 0.005). Pentobarbital sodium anesthesia induced marked hemodynamic changes in both sham-operated and bile duct-ligated rats. The latter group was especially sensitive to its effects; thus, comparison of cardiac output and portal tributary blood flow between anesthetized bile duct-ligated and sham-operated rats showed no significant differences. We conclude that the rat with cirrhosis due to chronic bile duct ligation is an excellent model for hemodynamic investigations but should be studied in the conscious state, since pentobarbital sodium anesthesia eliminates the hyperdynamic circulation.

Abstract-Erythrocyte aggregation, which plays an important role in the physiological behavior of blood fluidity, was found to be enhanced in hypertension and hypercholesterolemia. While the role of macromolecule bridging force has been widely described, cellular factors related to membrane sialic acid content, which might contribute to the negative charge of cell surface causing the repulsion of erythrocytes, have been less studied. Cell age-dependent changes in membrane sialic acid content (in micromoles per gram of integral membrane protein) were investigated in 24 normotensive and 24 hypertensive matched subjects, each divided into 2 identical subgroups according to a cutoff of 6.2 mmol/L serum cholesterol. A progressive and significant (PϽ0.001) decrease in membrane sialic acid content associated with an increase (PϽ0.001) of disaggregation shear rate threshold (laser reflectometry in the presence of dextran) were observed with increased erythrocyte density (erythrocytes fractionated by density using ultracentrifugation) in both normotensive and hypertensive groups regardless of the cholesterol level. However, disaggregation shear rate threshold was significantly higher and sialic acid content was lower (PϽ0.001) in both hypertensive and normotensive subjects with hypercholesterolemia compared with either normotensive or hypertensive subjects with low cholesterol, respectively. A high membrane sialic acid content variance, beginning in the younger erythrocytes, was due mainly to triglyceride and LDL cholesterol levels (R 2 ϭ0.49 for low, R 2 ϭ0.43 for middle, and R 2 ϭ0.54 for high densities, ie, young, mean, and senescent erythrocytes, respectively). We conclude that an early decrease in erythrocyte sialic acid content may influence the rheological properties of blood by increasing the adhesive energy of erythrocyte aggregates. (Hypertension. 1998;32:324-330.) Key Words: erythrocyte aggregation Ⅲ rheology Ⅲ sialic acid Ⅲ hypertension, essential Ⅲ hypercholesterolemia E rythrocyte aggregation is one of the main determinants influencing blood circulation at low shear rates by increasing blood viscosity and inducing "sludging" in the capillary.1 Aggregation of red blood cells is a reversible process that occurs when the bridging force due to the adsorption of macromolecules onto adjacent cell surfaces exceeds the disaggregation forces caused by electrostatic repulsion, membrane strain, and mechanical shearing. [1][2][3] An increase in erythrocyte aggregation was found to be associated with cardiovascular risk factors such as hypertension, 4 hyperlipoproteinemia, 5,6 and smoking 7 and in clinical situations such as myocardial ischemia, 8 thromboembolic states, 9 and retinal venous occlusion. 10 In general, most studies have focused on the ability of plasma proteins and various polymers to induce erythrocyte aggregation. We showed that in hypertension and hypercholesterolemia the increase in erythrocyte aggregation could be attributed to an increase in the concentration of plasma fibrinogen. 4,6 In addition, in ...

SummaryThe respective role of adhesive forces induced by fibrinogen and repulsive forces induced by erythrocyte sialic acid content on erythrocyte aggregation, was investigated in hypercholesterolemic and control subjects. Aggregation index (AI) and disaggregation shear rate threshold (³t) were determined in the presence of either autologous plasma or dextran. Compared with controls, fibrinogen (p <0.001) and aggregation parameters (AI p <0.01; ³t p <0.01) were higher in hypercholester-olemics while erythrocyte sialic acid content (p <0.001) was lower; in addition total serum sialic acid was increased (p <0.01). The aggregation properties of erythrocytes, independent of plasma environment using dextran as a bridging macromolecule, showed an enhanced disaggregation shear rate threshold and an inverse relationship with erythrocyte sialic acid content. We conclude that decreased erythrocyte sialic acid content may intensify the effect of fibrinogen on aggregation and disaggregation of erythrocytes and participate in the development of atherothrombotic complications.