ArticleThe Journal of infectious diseases2009
Relationship of cell-free hemoglobin to impaired endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria.
Article in The Journal of infectious diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 131 citations in OpenAlex.
- Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
- Inhaled nitric oxide and cognition in pediatric severe malaria: A randomized double-blind placebo controlled trial.PloS one · 2018Trial
- B-type natriuretic peptide and plasma hemoglobin levels following transfusion of shorter-storage versus longer-storage red blood cells: Results from the TOTAL randomized trial.American heart journal · 2017Trial
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- Impaired systemic tetrahydrobiopterin bioavailability and increased oxidized biopterins in pediatric falciparum malaria: association with disease severity.PLoS pathogens · 2015Trial
- A randomized pilot study of L-arginine infusion in severe falciparum malaria: preliminary safety, efficacy and pharmacokinetics.PloS one · 2013Trial
- Transfusion of stored autologous blood does not alter reactive hyperemia index in healthy volunteers.Anesthesiology · 2012Trial
- Carbon Quantum Dots with Tunable Size and Fluorescence Intensity for Development of a Nano-biosensor.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Histidine-rich protein II nanoparticle delivery of heme iron load drives endothelial inflammation in cerebral malaria.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Carboxyhemoglobin (COHb): Unavoidable Bystander or Protective Player?Antioxidants (Basel, Switzerland) · 2023Review
- Ultraviolet light oxidation of fresh hemoglobin eliminates aggregate formation seen in commercially sourced hemoglobin.Blood cells, molecules & diseases · 2023Article
- Lessons for the pathogenesis of vasospasm from a patient with sickle cell disease, moyamoya disease, subarachnoid hemorrhage, and 1 month of persistent vasospasm: illustrative case.Journal of neurosurgery. Case lessons · 2022Article
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- Knowlesi malaria: Human risk factors, clinical spectrum, and pathophysiology.Advances in parasitology · 2021Article
- The effect of blood transfusion on outcomes among African children admitted to hospital with Plasmodium falciparum malaria: a prospective, multicentre observational study.The Lancet. Haematology · 2020Observational
- Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics.PLoS computational biology · 2020Article
- The Role of Circulating Cell-Free Hemoglobin in Sepsis-Associated Acute Kidney Injury.Seminars in nephrology · 2020Review
- Heme Induces IL-6 and Cardiac Hypertrophy Genes Transcripts in Sickle Cell Mice.Frontiers in immunology · 2020Article
- Safety and Efficacy of Adjunctive Therapy With Artesunate in the Treatment of Severe Malaria: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2020Review
- Hypertension is associated with an increased risk for severe imported falciparum malaria: a tertiary care hospital based observational study from Berlin, Germany.Malaria journal · 2019Observational
21 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 5 countries.
Funding
Abstract
backgroundHemolysis causes anemia in falciparum malaria, but its contribution to microvascular pathology in severe malaria (SM) is not well characterized. In other hemolytic diseases, release of cell-free hemoglobin causes nitric oxide (NO) quenching, endothelial activation, and vascular complications. We examined the relationship of plasma hemoglobin and myoglobin to endothelial dysfunction and disease severity in malaria.
methodsCell-free hemoglobin (a potent NO quencher), reactive hyperemia peripheral arterial tonometry (RH-PAT) (a measure of endothelial NO bioavailability), and measures of perfusion and endothelial activation were quantified in adults with moderately severe (n = 78) or severe (n = 49) malaria and control subjects (n = 16) from Papua, Indonesia.
resultsCell-free hemoglobin concentrations in patients with SM (median, 5.4 micromol/L; interquartile range [IQR], 3.2-7.4 micromol/L) were significantly higher than in those with moderately severe malaria (2.6 micromol/L; IQR, 1.3-4.5 micromol/L) or controls (1.2 micromol/L; IQR, 0.9-2.4 micromol/L; P < .001). Multivariable regression analysis revealed that cell-free hemoglobin remained inversely associated with RH-PAT, and in patients with SM, there was a significant longitudinal association between improvement in RH-PAT index and decreasing levels of cell-free hemoglobin (P = .047). Cell-free hemoglobin levels were also independently associated with lactate, endothelial activation, and proinflammatory cytokinemia.
conclusionsHemolysis in falciparum malaria results in NO quenching by cell-free hemoglobin, and may exacerbate endothelial dysfunction, adhesion receptor expression and impaired tissue perfusion. Treatments that increase NO bioavailability may have potential as adjunctive therapies in SM.
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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.