Bepridil as an antisickling agent: membrane internalization and cell rigidity.

The calcium channel antagonist, bepridil, beta-(2-methylpropoxy)methyl-N-phenyl-N-(phenylmethyl)-1-pyrrol idineethanamine monochloride monohydrate, inhibits the sickling of deoxygenated sickle (SS) erythrocytes, as determined by light microscopy. The anti-sickling effect was seen only in dilute suspensions of red cells. In concentrated erythrocyte suspensions, sickling was not inhibited and measurements of hematocrit and cell density were unchanged by bepridil.

Modified celluloses for erythrocyte deformability fractionation.

Cellulose columns have been used to separate erythrocytes into deformability classes, but recoveries have been variable and incomplete. Columns of modified cellulose (propylaminocarbonylmethyl cellulose [PAC] and butylisourea cellulose [BIC]) were effective in increasing the recovery of both normal and sickle cells applied to the columns, with reasonable yields of rigid cells in the late fractions. In particular, sickle cells were recovered in 95% yield, and late eluting cells had a sharply reduced deformability index.

Isolation and quantitation of human erythrocyte deformability classes.

A new technique is described that fractionates erythrocytes according to their deformability. The method is a modification of the method of Beutler et al. (J Lab Clin Med 1976;88:328-33), in which small cellulose columns are used to remove white cells from blood samples.

Electron microscopic studies of the intracellular polymerization of sickle hemoglobin.

Transmission electron microscopy has been used to study intracellular sickle hemoglobin polymer in unfractionated cells from the arterial and venous blood of patients and after external deoxygenation. We detect polymerized hemoglobin in up to 10% of the cells in the venous circulation, especially in cells that are "cigar-shaped" and appear to be irreversibly sickled. We could not see well-defined polymer in mixed arterial samples; nevertheless, we found electron opaque spots, which could be ferritin granules, hemosiderin, or small aggregates of hemoglobin S.

The development of a filtration system for evaluating flow characteristics of erythrocytes.

A complete description of the pathophysiology of sickle cell disease requires a physiologically meaningful measurement of red cell deformability. We have designed and built a system which allows one to determine filtration characteristics of erythrocytes. A dilute red cell suspension is forced through a 3.