Subcutaneous microvasuclar-responses to hemodilution with a red cell substitute consisting of polyethyleneglycol-modified vesicles encapsulating hemoglobin

Hiromi Sakai, Amy G. Tsai, Heinz Kerger, Sung Ick Park, Shinji Takeoka, Hiroyuki Nishide, Eishun Tsuchida, Marcos Intaglietta

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Phospholipid vesicles encapsulating purified hemoglobin [Hb vesicles (HbV); diameter 259 ± 82 mm; oxygen affinity 31 mm Hg; [Hb] 5 and 10 g/dL] were developed to provide oxygen-carrying capacity to plasma expanders. Their function as a blood replacement was tested in the subcutaneous microvasculature of awake hamsters during severe hemodilution in which 80% of the red blood cell mass was substituted with suspensions of the vesicles in 5% human serum albumin (HSA) solution. Vesicles were tested with membranes that were unmodified (HbV/HSA) or conjugated with polyethyleneglycol (PEG) on the vesicular surface (PEG-HbV/HSA). The viscosity of 10 g/dL HbV/HSA was 8 cP at 358 s-1 owing to the intervesicular aggregation, while that of 10 g/dL PEG-HbV/HSA was 3.5 cP, since PEG chains inhibit aggregation. Both materials yielded normal mean arterial pressure, heart rate, and blood gas parameters at all levels of exchange, which could not be achieved with HSA alone. Subcutaneous microvascular studies showed that PEG-HbV/HSA significantly improved microhemodynamic conditions (flow rate, functional capillary density, vessel diameter, and oxygen tension) relative to unmodified HbV/HSA. Even though the enhancement of PEG modification did not achieved that functional characteristics of the blood-perfused microcirulation, PEG reduced vesicular aggregation and viscosity, improving microvascular perfusion relative to the unmodified type. These results highlight the significance of microvascular analysis in the design of red cell substitutes and the necessity of surface modification of HbV to prevent aggregation.

Original languageEnglish
Pages (from-to)66-78
Number of pages13
JournalJournal of Biomedical Materials Research
Volume40
Issue number1
DOIs
Publication statusPublished - 1998 Apr

Keywords

  • Hemoglobin
  • Liposome
  • Microcirculation
  • Polyethyleneglycol
  • Red cell substitute

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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