Hemorheological Effect Of Ticlopidine In Rats
Thrombosis and Haemostasis
The hemorheological effect of ticlopidine was studied in rats ex vivo. Ticlopidine (30-300 mg/kg) was orally given to rats. Heparinized blood samples were taken from the carotid artery under pentobarbital anesthesia 3 hr after the drug administration for measurement of whole blood viscosity (ELD type cone-plate viscometer), micropore filtrability of red cells (Nuclepore membrane, 5 µm), erythrocyte sedimentation rate (ESR), hematocrit (Ht) and plasma fibrinogen. Red cell deformability was
... rmability was measured by counting the shear stressinduced cap-form cells under a scanning electronmicroscope. Mechanical flexibility of red cells was also studied by measuring hemolysis caused by turbulant flow.Ticlopidine treatment caused a significant decrease in whole blood viscosity (9.13 ± 0.15 and 6.17 ± 0.08 versus 9.80 ± 0.18 and 6.74 ± 0.09 Cp in control at 19.2 sec-1and 76.8 sec-1, respectively) and a significant increase in micropore filtrability of the red cells (0.54 ± 0.01 versus 0.40 ± 0.02 ml/min in control) without any changes in ESR, Ht and plasma fibrinogen. Ticlopidine also significantly stimulated the shear stress-induced shape change of the red cells to cap-form cells (12.08 ± 0.13 versus 8.66 ± 0.23 % in control) and prevented mechanical hemolysis caused by a turbulant flow (16.8 ± 1 . 6 versus 30.5 ± 2.5 % in control).In addition to the platelet aggregation inhibitory action the hemorheological action of this agent may be useful for improving microcirculation and protecting red cells from mechanical disruption by turbulant blood flow.Increase in the adenylate cyclase and Mg2+-activated adenosine triphosphatase activities in red cell membranes may be associated with the effect of ticlopidine to increase red cell deformability.