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Transfusion. 2003 Apr;43(4):509-16.

MP4, a new nonvasoactive PEG-Hb conjugate.

Author information

  • 1Sangart, Inc., 11189 Sorrento Valley Road, Suite 104, San Diego, CA 92121, USA.

Abstract

BACKGROUND:

Vasoconstriction has been an obstacle to clinical development of Hb-based O2 carriers. It is proposed that this limitation can be overcome by increasing molecular size and oxygen affinity.

STUDY DESIGN AND METHODS:

Surface-modified Hb (MP4) was designed, whose properties are consistent with the theory that cell-free Hb engages autoregulatory vasoconstrictive responses to Hb diffusion in the plasma space ("facilitated diffusion"). Human Hb was modified by reaction first with 2-iminothiolane to add sulfhydryl groups and then with monofunctional maleimide- activated 5-kDa PEG.

RESULTS:

MP4 was found to have a molecular weight of 90 kDa, a molecular radius increased relative to native Hb (9.3 +/- 1.4 vs. 3.2 nm), high oxygen affinity (p50 approximately 5-6 mmHg), and a Bohr effect approximately half that of native human Hb (-0.24Deltalogp50/DeltapH). At 4.2 g per dL in Ringer's lactate, its viscosity was 2.5 cP, and its oncotic pressure was 50 mmHg. The t50 of 14C-MP4 in rats was approximately 24 hours. No significant elevation in mean arterial pressure was observed.

CONCLUSION:

MP4 appears to be free of a pressor effect, a major limitation to the development of a safe and effective RBC substitutes in the past.

PMID:
12662285
[PubMed - indexed for MEDLINE]
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