Increased red blood cell deformability due to isoxsuprine administration decreases platelet adherence in a perfusion chamber: a double-blind cross-over study in patients with intermittent claudication

Platelet transport towards the vessel wall is influenced by the hematocrit, red blood cell (RBC) size, and shape. Recent in vitro studies have indicated that RBC deformability may also influence platelet transport. The observation that isoxsuprine, a known vasodilating drug, caused increased RBC deformability in vitro and decreased platelet transport in vitro prompted us to study the effects of this drug in vivo. The study was performed in a double-blind cross- over study of isoxsuprine v placebo in ten patients with peripheral arterial insufficiency. RBC deformability was estimated from viscosity measurements using the blood viscosity equation of Dintenfass and expressed as T value. Platelet transport was studied in an annular perfusion chamber according to Baumgartner. Human umbilical arteries were used as blood vessels. Perfusion studies were performed with whole blood or with RBCs of the patients mixed with normal platelets and plasma at a standardized hematocrit and platelet count. An increase in RBC deformability concomitant with a decrease in platelet adherence was observed in patients on isoxsuprine with a drop in T value of approximately 0.06 (from 0.91 toward 0.86), and a concomitant decrease in platelet adherence of 20% to 40%. These observations differed significantly from the results in the placebo group and showed a significant group-period interaction at the cross-over of medication (analysis of variance). The effects on platelet adherence were observed at high vessel wall shear rate (1,800 s-1) with perfusates consisting of patients' RBCs and donor plasma and platelets at standardized hematocrit and platelet count. No differences were observed under these conditions at a shear rate of 300 s-1. When whole blood of patients was used, nonsignificant effect was observed at shear rates of 300 s-1 and 1,800 s-1. This was probably caused by the added noise due to variations in hematocrit and platelet number. These data demonstrate that isoxsuprine increases RBC deformability, and they suggest the possibility of decreasing platelet-vessel wall interaction in vivo by manipulation of RBC deformability.