HBOC vasoactivity

Interplay between nitric oxide scavenging and capacity to generate bioactive nitric oxide species

Pedro Cabrales, Joel M. Friedman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Significance: Despite many advances in blood substitute research, the development of materials that are effective in maintaining blood volume and oxygen delivery remains a priority for emergency care and trauma. Clinical trials on hemoglobin (Hb)-based oxygen carriers (HBOCs) have not provided information on the mechanism of toxicity, although all commercial formulations have safety concerns. Specifically, it is important to reconcile the different hypotheses of Hb toxicity, such as nitric oxide (NO) depletion and oxidative reactions, to provide a coherent molecular basis for designing a safe HBOC. Recent Advances: HBOCs with different sizes often exhibit differences in the degree of HBOC-induced vasoactivity. This has been attributed to differences in the degree of NO scavenging and in the extent of Hb extravasation. Additionally, it is appears that Hb can undergo reactions that compensate for NO scavenging by generating bioactive forms of NO. Critical Issues: Engineering modifications to enhance bioactive NO production can result in diminished oxygen delivery by virtue of increased oxygen affinity. This strategy can prevent the HBOC from fulfilling the intended goal on preserving oxygenation; however, the NO production effects will increase perfusion and oxygen transport. Future Directions: Hb modifications influence NO scavenging and the capacity of certain HBOCs to compensate for NO scavenging through nitrite-mediated reactions that generate bioactive NO. Based on the current understanding of these NO-related factors, possible synthetic strategies are presented that address how HBOC formulations can be prepared that: (i) effectively deliver oxygen, (ii) maintain tissue perfusion, and (iii) limit/reverse underlying inflammation within the vasculature. Antioxid. Redox Signal. 18, 2284-2297.

Original languageEnglish (US)
Pages (from-to)2284-2297
Number of pages14
JournalAntioxidants and Redox Signaling
Volume18
Issue number17
DOIs
StatePublished - Jun 10 2013

Fingerprint

Scavenging
Nitric Oxide
Oxygen
Hemoglobins
Toxicity
Perfusion
Blood Substitutes
Oxygenation
Emergency Medical Services
Nitrites
Blood Volume
Oxidation-Reduction
Blood
Clinical Trials
Tissue
Inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

HBOC vasoactivity : Interplay between nitric oxide scavenging and capacity to generate bioactive nitric oxide species. / Cabrales, Pedro; Friedman, Joel M.

In: Antioxidants and Redox Signaling, Vol. 18, No. 17, 10.06.2013, p. 2284-2297.

Research output: Contribution to journalArticle

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