4.2 Article

In vivo reduction of cell-free methemoglobin to oxyhemoglobin results in vasoconstriction in canines

Journal

TRANSFUSION
Volume 53, Issue 12, Pages 3149-3163

Publisher

WILEY
DOI: 10.1111/trf.12162

Keywords

-

Categories

Funding

  1. NIH [HL058091, HL098032, RO1HL096973, P01HL103455]
  2. Institute for Transfusion Medicine
  3. Hemophilia Center of Western Pennsylvania
  4. US government

Ask authors/readers for more resources

BackgroundCell-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 MethodsTwenty beagles were challenged with 1-hour similar infusions of (200mol/L) metHb (n=5), oxyHb (n=5), albumin (n=5), or saline (n=5). Measurements were taken over 3 hours. ResultsInfusions 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 3hr; 276% 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). ConclusionThese 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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.2
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available