Oxidative Stress Increases Erythrocyte Sensitivity to Shear‐Mediated Damage

Abstract

Patients receiving mechanical circulatory support often present with heightened inflammation and free radical production associated with pre-existing conditions in addition to that which is due to blood interactions with nonbiological surfaces. The aim of this experimental laboratory study was to assess the deformability of red blood cells (RBC) previously exposed to oxygen free radicals and determine the susceptibility of these cells to mechanical forces. In the present study, RBC from 15 healthy donors were washed and incubated for 60 min at 37°C with 50 µM phenazine methosulfate (PMS; an agent that generates superoxide within RBC). Incubated RBC and negative controls were assessed for their deformability and susceptibility to mechanical damage (using ektacytometry) prior to the application of shear stress, and also following exposure to 25 different shear conditions of varied magnitudes (shear stress 1, 4, 16, 32, 64 Pa) and durations (1, 4, 16, 32, 64 s). The salient findings demonstrate that incubation with PMS impaired important indices of RBC deformability indicating altered cell mechanics by ∼19% in all conditions (pre- and postexposure to shear stress). The typical trends in shear-mediated changes in RBC susceptibility to mechanical damage, following conditioning shear stresses, were maintained for PMS incubated and control conditions. We demonstrated that free radicals hinder the ability of RBC to deform; however, RBC retained their typical mechanical response to shear stress, albeit at a decreased level compared with control following exposure to PMS. Our findings also indicate that low shear exposure may decrease cell sensitivity to mechanical damage upon subsequent shear stress exposures. As patients receiving mechanical circulatory support have elevated exposure to free radicals (which limits RBC deformability), concomitant exposure to high shear environments needs to be minimized.

The Red Blood Cell—Inflammation Vicious Circle in Sickle Cell Disease

“…All these changes may affect the fragility of RBCs. For instance, McNamee et al (99) recently showed that phenazine methosulfate (an agent that generates superoxide anion within RBCs) decreased RBC deformability and increased the sensitivity of RBCs to shear-mediated damage. Hierso et al (100) compared the biophysical response of healthy and SCD RBCs to in-vitro oxidative stress, using tbutyl hydroperoxide (TBHP).…”

Study on Oxidation Stability and Oxygen Affinity of Hemoglobin During Storage

“…HBOCs in practice were expected to maintain stability in long production and storage processes . However, in the absence of an antioxidant system, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) , the heme iron of Hb is easily oxidized to the ferric state (methemoglobin, metHb), which cannot carry oxygen . Therefore, research on oxidation is essential to improve the capability of Hb as an HBOC.…”

Sublethal mechanical trauma alters the electrochemical properties and increases aggregation of erythrocytes

“…The impact of shear removal of membrane-bound sialic acid content may also explain the decreased RBC deformability and increased membrane rigidity observed in other studies (Horobin et al, 2017;McNamee et al, 2017;McNamee et al, 2016b;Simmonds et al, 2014;Simmonds and Meiselman, 2017). As sialic acid is negatively ionized, and cytosolic hemoglobin is positively charged, membrane-bound sialic acid is proposed to be an important regulator of hemoglobin distribution in the cytoplasm, thus also playing a role in maintaining the oxygen carrying capacity of RBCs (Huang et al, 2016).…”

“…complications have been reported with long-term use that are suggestive of blood damage and malfunction, without remarkable hemolysis. This damage, which is due to bloodinteraction with non-physiological environments (i.e., contact with foreign surfaces, elevated shear forces, turbulence and cavitation), can cause dangerous complications of altered perfusion and rheological properties of blood (Horobin et al, 2017;McNamee et al, 2017;McNamee et al, 2016b;Ruggeri et al, 2006). The observed complications of hemorrhagic events, thrombotic events, tissue ischemia and anemia, leading to multi-system organ failure (Kirklin et al, 2014), may be partially explained by altered RBC aggregation behavior.…”