Changes in shear-induced hemolysis due to blood additives: synthetic biopolymers and asthma drugs

Abstract

Mechanical fragility of human red blood cells was evaluated by shearing the blood between rotating polyethylene disks and measuring the timedependent release of hemoglobin. Several blood additives were tested for their effect on this hemolysis: (a) two synthetic polynucleotides (polyadenylate and polycytidylate) as biopolymers with purine and pyrimidine moieties, respectively; (b) two low-molecular-weight purine derivatives (the drug theophylline and uric acid). It was found that polyadenylate always increased hemolysis, polycytidylate often reduced it, theophylline always reduced it, and uric acid was always ineffective. Drug localization data on theophylline showed a large uptake of the additive by cell membranes, the degree of hemolysis protection being proportional to the mass of the drug absorbed. Supplementary cell characterization by resistive pulse spectroscopy documented that the protective drugs caused cell volumes to increase, deformability to decrease, and osmotic fragility to decrease. Chemical and mechanical mechanisms for changes in mechanical fragility are proposed.