Evidence map›Paper›PMID 23488474›Full record

ArticleTransfusion2013

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

Dong Wang, Barbora Piknova, Steven B Solomon, Irene Cortes-Puch, Steven J Kern, Junfeng Sun, Tamir Kanias, Mark T Gladwin, Christine Helms, Daniel B Kim-Shapiro and 2 more

Open access · greenAbstract read
In one paragraph

Article in Transfusion, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Red blood cell storage lesion: causes and potential clinical consequences.Blood transfusion = Trasfusione del sangue · 2019
    Review
  7. Article
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Dong WangCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; Division of Pulmonary, Allergy and Critical Care Medicine and the Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Physics and the Translational Science Center, Wake Forest University, Winston-Salem, North Carolina; Anesthesia and Critical Care Medicine Department, West China Hospital of Sichuan University, Cheng Du, China; Critical Care Medicine Department, Hospital Universitario de Getafe, Getafe, Madrid, Spain.
Barbora Piknova
Steven B Solomon
Irene Cortes-Puch
Steven J Kern
Junfeng Sun
Tamir Kanias
Mark T Gladwin
Christine Helms
Daniel B Kim-Shapiro
Alan N Schechter
Charles Natanson
Wake Forest University · USHospital Universitario de Getafe · ESNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health Clinical Center · USSichuan University · CNWest China Hospital of Sichuan University · CN

Funding

Vascular Subphenotypes of Lung DiseaseP01HL103455 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLADWIN, MARK T · 2011 to 2020
$26.1M
Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide HomeostasisR01HL098032 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mark T Gladwin · 2009 to 2026
$12.5M
Clinical Applications of Nitrite and NitrateZIADK025104 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI SCHECHTER, ALAN · 2009 to 2025
$10.4M
Nitric Oxide Transport By HemoglobinZIADK025093 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI SCHECHTER, ALAN · 2009 to 2022
$7.2M
Effects of Nitric Oxide in Sickle Cell BloodR37HL058091 · NHLBI · WAKE FOREST UNIVERSITY · PI KIM-SHAPIRO, DANIEL B · 2007 to 2016
$3.5M
Effects of Nitric Oxide in Sickle Cell BloodR01HL058091 · NHLBI · WAKE FOREST UNIVERSITY · PI KIM-SHAPIRO, DANIEL B · 2002 to 2006
$1.6M
Myoglobin as a Nitrite Reductase that Regulates Hypoxic Cardiac NO SignalingR01HL096973 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLADWIN, MARK T, SHIVA, SRUTI · 2010 to 2013
$1.5M
MECHANISM AND KINETICS OF SICKLE CELL HEMOGLOBINR29HL058091 · NHLBI · WAKE FOREST UNIVERSITY · PI KIM-SHAPIRO, DANIEL B · 1998 to 2002
$260k
The Effect of Angeli's salt on Acute Hemolysis in a Canine ModelZIACL008096 · CLC · CLINICAL CENTER · PI NATANSON, CHARLES · 2009 to 2014
$0k
Intramural NIH HHS Z99 DA999999Intramural NIH HHS Z99 DK999999Intramural NIH HHS Z99 OD999999NHLBI NIH HHS HL058091NHLBI NIH HHS HL098032NHLBI NIH HHS P01 HL103455NHLBI NIH HHS P01HL103455NHLBI NIH HHS R01 HL058091NHLBI NIH HHS R01 HL096973NHLBI NIH HHS R01HL096973NHLBI NIH HHS R01 HL098032NHLBI NIH HHS R29 HL058091NHLBI NIH HHS R37 HL058091
6 · The paper itself

Abstract

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 (200 μmol/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 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).

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.

Indexed as

AlbuminsAnimalsBlood PressureDogsMethemoglobinNitric OxideOxyhemoglobinsRandom AllocationVasoconstrictionAlbuminsMethemoglobinNitric OxideOxyhemoglobins

Identifiers

PMID23488474
PMCPMC3686899
OpenAlexW1900275564

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.