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In vivo reduction of cell‐free methemoglobin to oxyhemoglobin results in vasoconstriction in canines
Author(s) -
Wang Dong,
Piknova Barbora,
Solomon Steven B.,
CortesPuch Irene,
Kern Steven J.,
Sun Junfeng,
Kanias Tamir,
Gladwin Mark T.,
Helms Christine,
KimShapiro Daniel B.,
Schechter Alan N.,
Natanson Charles
Publication year - 2013
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12162
Subject(s) - methemoglobin , hemoglobin , vasoconstriction , chemistry , nitric oxide , in vivo , hematocrit , saline , endocrinology , medicine , biochemistry , biology , microbiology and biotechnology
Background Cell‐free hemoglobin ( Hb ) in the vasculature leads to vasoconstriction and injury. Proposed mechanisms have been based on nitric oxide ( NO ) scavenging by oxyhemoglobin ( oxyHb ) or processes mediated by oxidative reactions of methemoglobin ( metHb ). To clarify this, we tested the vascular effect and fate of oxyHb or metHb infusions. Study Design and Methods Twenty beagles were challenged with 1‐hour similar infusions of (200 μmol/L ) metHb (n = 5), oxyHb (n = 5), albumin (n = 5), or saline (n = 5). Measurements were taken over 3 hours. Results Infusions of the two pure Hb species resulted in increases in mean arterial blood pressure ( MAP ), systemic vascular resistance index, and NO consumption capacity of plasma (all p < 0.05) with the effects of oxyHb being greater than that from metHb ( MAP ; increase 0 to 3 hr; 27 ± 6% vs. 7 ± 2%, respectively; all p < 0.05). The significant vasoconstrictive response of metHb (vs. albumin and saline controls) was related to in vivo autoreduction of metHb to oxyHb , and the vasoactive Hb species that significantly correlated with MAP was always oxyHb , either from direct infusion or after in vivo reduction from metHb . Clearance of total Hb from plasma was faster after metHb than oxyHb infusion (p < 0.0001). Conclusion These findings indicate that greater NO consumption capacity makes oxyHb more vasoactive than metHb . Additionally, metHb is reduced to oxyHb after infusion and cleared faster or is less stable than oxyHb . Although we found no direct evidence that metHb itself is involved in acute vascular effects, in aggregate, these studies suggest that metHb is not inert and its mechanism of vasoconstriction is due to its delayed conversion to oxyHb by plasma‐reducing agents.