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Citations to this article

Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin
Peter C. Minneci, … , Mark T. Gladwin, Steven B. Solomon
Peter C. Minneci, … , Mark T. Gladwin, Steven B. Solomon
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3409-3417. https://doi.org/10.1172/JCI25040.
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Research Article Vascular biology Article has an altmetric score of 9

Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin

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Abstract

During intravascular hemolysis in human disease, vasomotor tone and organ perfusion may be impaired by the increased reactivity of cell-free plasma hemoglobin (Hb) with NO. We experimentally produced acute intravascular hemolysis in a canine model in order to test the hypothesis that low levels of decompartmentalized or cell-free plasma Hb will severely reduce NO bioavailability and produce vasomotor instability. Importantly, in this model the total intravascular Hb level is unchanged; only the compartmentalization of Hb within the erythrocyte membrane is disrupted. Using a full-factorial design, we demonstrate that free water–induced intravascular hemolysis produces dose-dependent systemic vasoconstriction and impairs renal function. We find that these physiologic changes are secondary to the stoichiometric oxidation of endogenous NO by cell-free plasma oxyhemoglobin. In this model, 80 ppm of inhaled NO gas oxidized 85–90% of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous NO scavenging by cell-free Hb. As a result, the vasoconstriction caused by acute hemolysis was attenuated and the responsiveness to systemically infused NO donors was restored. These observations confirm that the acute toxicity of intravascular hemolysis occurs secondarily to the accelerated dioxygenation reaction of plasma oxyhemoglobin with endothelium-derived NO to form bioinactive nitrate. These biochemical and physiological studies demonstrate a major role for the intact erythrocyte in NO homeostasis and provide mechanistic support for the existence of a human syndrome of hemolysis-associated NO dysregulation, which may contribute to the vasculopathy of hereditary, acquired, and iatrogenic hemolytic states.

Authors

Peter C. Minneci, Katherine J. Deans, Huang Zhi, Peter S.T. Yuen, Robert A. Star, Steven M. Banks, Alan N. Schechter, Charles Natanson, Mark T. Gladwin, Steven B. Solomon

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 Total
Citations: 1 9 7 6 8 8 11 6 5 6 7 8 9 14 6 7 7 8 4 7 144
Citation information
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Citations to this article in year 2014 (8)

Title and authors Publication Year
Autologous Transfusion of Stored Red Blood Cells Increases Pulmonary Artery Pressure
L Berra, R Pinciroli, CP Stowell, L Wang, B Yu, BO Fernandez, M Feelisch, C Mietto, EA Hod, D Chipman, M Scherrer-Crosbie, KD Bloch, WM Zapol
American journal of respiratory and critical care medicine 2014
Elevated Pulse Pressure is Associated with Hemolysis, Proteinuria and Chronic Kidney Disease in Sickle Cell Disease
EM Novelli, M Hildesheim, C Rosano, R Vanderpool, M Simon, GJ Kato, MT Gladwin, D Guerrot
PloS one 2014
Does prolonged storage of red blood cells cause harm?
WA Flegel, C Natanson, HG Klein
British Journal of Haematology 2014
Angiotensin-Converting Enzyme Inhibitor Captopril Reverses the Adverse Cardiovascular Effects of Polymerized Hemoglobin
T Li, R Zhou, Y Yao, Q Yang, C Zhou, W Wu, Q Li, Z You, X Zhao, L Yang, C Li, D Zhu, Y Qiu, M Luo, Z Tan, H Li, Y Chen, G Gong, Y Feng, K Dian, J Liu
Antioxidants & Redox Signaling 2014
Transfusion of older stored blood worsens outcomes in canines depending on the presence and severity of pneumonia: Older Transfused RBCs Increase Sepsis Risk
D Wang, I Cortés-Puch, J Sun, SB Solomon, T Kanias, KE Remy, J Feng, M Alimchandani, M Quezado, C Helms, A Perlegas, MT Gladwin, DB Kim-Shapiro, HG Klein, C Natanson
Transfusion 2014
Transfusion related morbidity in premature babies: Possible mechanisms and implications for practice
Keith James Collard
World Journal of Clinical Pediatrics 2014
Haptoglobin, hemopexin, and related defense pathways—basic science, clinical perspectives, and drug development
DJ Schaer, F Vinchi, G Ingoglia, E Tolosano, PW Buehler
Frontiers in physiology 2014
Elevation of Plasma Cell-Free Hemoglobin in Pulmonary Arterial Hypertension
EL Brittain, DR Janz, ED Austin, JA Bastarache, LA Wheeler, LB Ware, AR Hemnes
Chest 2014

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