THE SHEAR STRESSED NORMAL ERYTHROCYTE AS A MODEL DEFECT FOR DECREASED RED CELL DEFORMABILITY

[摘要] Exposure of normal erythrocytes to super-physiologic but subhemolytic shear stresses results in decreased red cell deformability. This model defect has helped pinpoint possible factors effecting similar cell damage from currently used medical devices. Red cell ATP is found not to be a primary determinant of this phenomenon. Intracellular calcium, as measured by a modification of Harrison and Long;;s procedure, is increased by 35 and 55% above control levels following exposure to shear stresses of 1000 and 1300 dynes/cm(;;2) for two minutes, and is associated with decreasing deformability. The disparate magnitudes of shear-related sodium influx and potassium efflux indicate genesis of a hyperpolarized membrane during shear, which apparently enhances calcium uptake. No significant changes are found for intracellular magnesium, 2,3-diphosphoglycerate or mean cell volume. Major results of the model studies are verified clinically by measurements on red cells from patients with chronic renal failure receiving hemodialysis or for patients with prosthetic cardiac valves. A strong correlation (r = .91, p < .001) has been found for our deformability indicator with intracellular calcium for the prosthetic heart valve patients; other correlations for this group are found with patient;;s values for hematocrit, serum lactate dehydrogenase, and percentage of abnormal cells. These findings imply that deformability is indeed an important pathophysiological quantity. Erythrocyte deformability for this work is determined by the pressure drop during constant volumetric flowrate filtration of a red cell suspension through the 3 (mu)m diameter pores of a Nuclepore filter. The zero time pressure drop from the linear portion of this curve is the deformability indicator P(,0). Pressure vs. filtration time curve characteristics of initial pressure drop, transient response, and a slight steady-state positive slope are attributed to membrane viscosity, the experimental setup, and pore plugging, respectively. Theoretical models lead to an estimate of the coefficient of surface viscosity for the red cell membrane (6(.)10(;;-3) dyn sec/cm) and to a curve fit for pressure as a function of filtration time.

[发布机构] Rice University