Sodium bicarbonate alters protein stability and blood coagulability in a simulated Impella purge gap model

• Published in: Artificial organs 2023-06, Vol.47 (6), p.971-981
• Main Authors: Ammann, Kaitlyn R., Ding, Jun, Gilman, Vladimir, Corbett, Scott, Slepian, Marvin J.
• Format: Article
• Language: English
• Subjects: Anticoagulants; Anticoagulants - pharmacology; Anticoagulants - therapeutic use; Biofouling; Biopolymer denaturation; Blood circulation; Blood Coagulation; Blood pumps; Clotting; Dextrose; Heparin; Heparin - pharmacology; Heparin - therapeutic use; High performance liquid chromatography; Human serum albumin; Humans; Liquid chromatography; mechanical circulatory support; Mixtures; Monomers; pH effects; Protein denaturation; Protein Stability; Proteins; purge; Serum albumin; Simulation; Sodium; Sodium Bicarbonate; Stability analysis; Stirring
• ISSN: 0160-564X; 1525-1594
• DOI: 10.1111/aor.14497

Background The Impella® microaxial blood pumps utilize purge fluid containing heparin to prevent biofouling of internal surfaces. Purge fluid interfaces with blood or blood components at two notable internal locations: (1) 5–8 μm radial gap (“Radial Gap” or “Gap 1”) between the motor shaft and bearing, a site accessible by blood proteins or small molecules; and (2) 100 μm axial gap (“Axial Gap” or “Gap 2”) between the impeller rotor and bearing, the site of mixing with larger circulating blood components. Despite its efficacy, heparin in the purge fluid complicates overall patient anticoagulation management. Here, we investigate sodium bicarbonate as an alternative to heparin in the purge fluid in a simulated purge gap micro‐environment. Methods To assess protein stability simulated at Gap 1, human serum albumin (HSA; 40 mg/ml) species were quantified utilizing size exclusion liquid chromatography (SEC‐HPLC) after stirring with purge fluid (5% dextrose in water (D5W) with heparin (25 U/ml) or sodium bicarbonate (25 or 50 mEq/L)) over a 24‐h period. pH measurements were taken immediately prior to stirring. Mixing between blood and purge fluid at Gap 2 was mimicked in vitro utilizing a 60:40 blood: purge fluid ratio. Purge fluid consisted of D5W with or without sodium bicarbonate (25 or 50 mEq/L). Human citrated blood samples were freshly collected with or without the addition of heparin (5 U/ml). Coagulability was determined via thromboelastography (TEG). pH measurements of blood mixtures were taken immediately before and after TEG analysis. Results Sodium bicarbonate alone or synergistically with heparin was effective in increasing protein stability, increasing pH, and reducing coagulability. In the Gap 1 model, sodium bicarbonate led to preservation of HSA monomer after 24 h mixing, with monomer composing 88.3 ± 2.3% and 88.6 ± 0.9% of total HSA species for 25 or 50 mEq/L sodium bicarbonate, respectively. Only 60.4 ± 4.3% monomer was observed with D5W alone (p