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Hemodialysis-Induced Release of Hemoglobin Limits Nitric Oxide Bioavailability and Impairs Vascular Function

Meyer, Christian, Heiss, Christian, Drexhage, Christine, Kehmeier, Eva S., Balzer, Jan, Mühlfeld, Anja, Merx, Marc W., Lauer, Thomas, Kühl, Harald, Floege, Jürgen , Kelm, Malte and Rassaf, Tienush (2010) Hemodialysis-Induced Release of Hemoglobin Limits Nitric Oxide Bioavailability and Impairs Vascular Function Journal of the American College of Cardiology, 55 (5). pp. 454-459.

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Abstract

Objectives This study sought to characterize the impact of hemodialysis (HD)-induced release of hemoglobin on the bioavailability of nitric oxide (NO) and endothelial function.

Background Patients on chronic HD suffer from endothelial dysfunction and a massively increased risk for cardiovascular events. Although dialysis-dependent and -independent factors are discussed, the exact mechanisms are not fully understood.

Methods In 14 HD patients (56 ± 15 years of age), endothelial function was determined by measuring flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound before and after treatment. The NO consumption activity of plasma isolated from patients before and after hemodialysis was studied with an NO-sensitive electrode.

Results HD impaired FMD (3.5 ± 2.6% to 1.7 ± 1.4%, p = 0.04) without affecting brachial artery diameter (4.7 ± 0.6 mm vs. 4.4 ± 0.9 mm, p = 0.27). This was accompanied by an increase in cell-free plasma hemoglobin (196 ± 43 mg/l to 285 ± 109 mg/l, p = 0.01), which led to a decrease in the bioavailability of free NO by more than 70%. Oxidation of the released plasma ferrous hemoglobin prevented the consumption of NO. The amount of decompartmentalized hemoglobin after HD correlated inversely with the change in FMD (r = −0.65, p = 0.041).

Conclusions Our data support a role of HD-induced release of hemoglobin in the pathogenesis of endothelial dysfunction in patients with end-stage renal disease. Approaches that oxidize free plasma hemoglobin may restore NO bioavailability and may have potential beneficial effects on vascular function. (Influence of Hemodialysis on Endothel-Depending Dilatation of Peripheral Arteries; NCT00764192)

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Clinical and Experimental Medicine
Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Faculty of Health and Medical Sciences
Authors :
NameEmailORCID
Meyer, Christian
Heiss, Christianc.heiss@surrey.ac.uk
Drexhage, Christine
Kehmeier, Eva S.
Balzer, Jan
Mühlfeld, Anja
Merx, Marc W.
Lauer, Thomas
Kühl, Harald
Floege, Jürgen
Kelm, Malte
Rassaf, Tienush
Date : 2 February 2010
Identification Number : 10.1016/j.jacc.2009.07.068
Copyright Disclaimer : © 2010 by the American College of Cardiology Foundation
Uncontrolled Keywords : Nitric oxide; Endothelial function; Hemodialysis; Hemolysis
Depositing User : Diane Maxfield
Date Deposited : 14 Aug 2018 12:04
Last Modified : 14 Aug 2018 12:23
URI: http://epubs.surrey.ac.uk/id/eprint/848924

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