Hemoglobin encapsulation in vesicles retards NO and CO binding and O 2 release when perfused through narrow gas-permeable tubes

Hiromi Sakai*, Naoto Okuda, Atsushi Sato, Tatsuya Yamaue, Shinji Takeoka, Eishun Tsuchida

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Intravenous administration of cell-free Hb induces vasoconstriction and circulatory disorders, presumably because of the intrinsic affinities to endogenous nitric oxide (NO) and carbon monoxide (CO) as vasorelaxation factors and because of the facilitated O2 release that might induce autoregulatory vasoconstriction. We examined these gas reactions when Hb-containing solutions of four kinds were perfused through artificial narrow tubes at a practical Hb concentration (10 g/dl). Purified Hb solution, polymerized bovine Hb (PolyBHb), encapsulated Hb [Hb-vesicles (HbV), 279 nm], and red blood cells (RBCs) were perfused through a gas-permeable narrow tube (25 μm inner diameter) at 1 mm/s centerline velocity. The level of reactions was determined microscopically based on the visible-light absorption spectrum of Hb. When the tube was immersed in NO and CO atmospheres, both NO binding and CO binding of deoxygenated Hb (deoxy-Hb) and PolyBHb in the tube was faster than those of HbV and RBCs, and HbV and RBCs showed almost identical binding rates. When the tube was immersed in a N2 atmosphere, oxygenated Hb and PolyBHb showed much faster O2 release than did HbV and RBCs. PolyBHb showed a faster reaction than Hb because of the lower O2 affinity of PolyBHb than Hb. The diffusion process of the particles was simulated using Navier-Stokes and Maxwell-Stefan equations. Results clarified that small Hb (6 nm) diffuses laterally and mixes rapidly. However, the large-dimension HbV shows no such rapid diffusion. The purely physicochemical differences in diffusivity of the particles and the resulting reactivity with gas molecules are one factor inducing biological vasoconstriction of Hb-based oxygen carriers.

Original languageEnglish
Pages (from-to)H956-H965
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3
Publication statusPublished - 2010 Mar


  • Blood substitutes
  • Erythrocytes
  • Gas biology
  • Liposome
  • Microcirculation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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