Apohemoglobin Haptoglobin Complexes Attenuate the Hypertensive Response to Low Molecular Weight Polymerized Hemoglobin
- Type: Conference Presentation
- Conference Type: AIChE Annual Meeting
- Presentation Date: November 16, 2020
- Duration: 15 minutes
- Skill Level: Intermediate
- PDHs: 0.30
Methodology: In this study, we synthesized a low MW PolyHb. The hydrodynamic diameter, O2 affinity, and size distribution were measured. The Hp used for this study was purified from human Cohn Fraction IV derived from pooled human plasma. The resulting Hp contained both Hp2-1 and Hp2-2 phenotypes. Hp binding to PolyHb was confirmed in vitro with stop-flow fluorescence spectrometry and size exclusion chromatography. Hp was stabilized by binding it to heme-free Hb (apoHb) in the form of an apoHb-Hp complex. Systemic parameters, including heart rate (HR) and mean arterial pressure (MAP), were used as indicators of reduced hypertension. Additionally, intravital microscopy was used to examine how co-administration of apoHb-Hp influences functional capillary density (FCD), vascular tone, and blood flow.
Results and Conclusions: Polymerization of Hb resulted in decreased O2 affinity and increased MW. PolyHb contained a significant fraction of low MW species (< 250 kDa). Hp was able to bind low MW PolyHb. Hp binding resulted in a significant increase in the average size of PolyHb. In the apoHp-Hb group, there was negligible change in MAP, FCD, HR, and microhemodynamics compared to baseline conditions. When compared to the systemic and microcirculatory changes observed in the apoHb and saline groups, the relatively small changes in the apoHb-Hp group indicate that Hp-based species may serve as materials to counteract the pressor effects of low MW HBOCs that are capable of binding to Hp. Thus, the administration of a Hb scavenging apoHb-Hp solution maintained physiologic hemodynamics during the transfusion of PolyHb.
|AIChE Member Credits||0.5|
|AIChE Graduate Student Members||Free|
|AIChE Undergraduate Student Members||Free|