This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Meyer, C. Articles by Rassaf, T. Search for Related Content PubMed PubMed Citation Articles by Meyer, C. Articles by Rassaf, T. Related Collections Related Articles

CLINICAL RESEARCH: VASCULAR DISEASE

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

Christian Meyer, MD^_*, Christian Heiss, MD^_*, Christine Drexhage, MSc^_*, Eva S. Kehmeier, MD^_*, Jan Balzer, MD^_*, Anja Mühlfeld, MD, Marc W. Merx, MD^_*, Thomas Lauer, MD^_*, Harald Kühl, MD, Jürgen Floege, MD, Malte Kelm, MD^_* and Tienush Rassaf, MD^_*,_*

^_* Division of Cardiology, Pulmonology and Vascular Medicine, University Hospital, Duesseldorf, Germany
Division of Nephrology and Immunology, Rheinisch-Westfälisch-Technische-Hochschule Aachen, Medical Faculty, Aachen, Germany
Division of Cardiology and Pulmonology, Rheinisch-Westfälisch-Technische-Hochschule Aachen, Medical Faculty, Aachen, Germany

Manuscript received April 9, 2009; revised manuscript received July 7, 2009, accepted July 12, 2009.

^_* Reprint requests and correspondence: Dr. Tienush Rassaf, Department of Medicine, Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany (Email: Tienush.Rassaf{at}med.uni-duesseldorf.de).

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 [ClinicalTrials.gov] )

Key Words: nitric oxide • endothelial function • hemodialysis • hemolysis

Abbreviations and Acronyms   ESRD = end-stage renal disease   FeCN = ferricyanide   FMD = flow-mediated dilation   GTN = glycerol trinitrate   HD = hemodialysis   NO = nitric oxide

Related Articles

Hemodialysis Hyperhemolysis: A Novel Mechanism of Endothelial Dysfunction and Cardiovascular Risk?

Chenell L. Donadee and Mark T. Gladwin
J. Am. Coll. Cardiol. 2010 55: 460-462. [Full Text] [PDF]

This article has been cited by other articles:

				I. C. Vermeulen Windsant, S. J. Hanssen, W. A. Buurman, and M. J. Jacobs Cardiovascular surgery and organ damage: Time to reconsider the role of hemolysis J. Thorac. Cardiovasc. Surg., July 1, 2011; 142(1): 1 - 11. [Full Text] [PDF]

				A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, G. K. Feld, B. H. Greenberg, J. Hall, M. Hlatky, W. Y. W. Lew, J. A. C. Lima, A. S. Maisel, et al. Highlights of the Year in JACC 2010 J. Am. Coll. Cardiol., January 25, 2011; 57(4): 480 - 514. [Full Text] [PDF]

				C. L. Donadee and M. T. Gladwin Hemodialysis Hyperhemolysis: A Novel Mechanism of Endothelial Dysfunction and Cardiovascular Risk? J. Am. Coll. Cardiol., February 2, 2010; 55(5): 460 - 462. [Full Text] [PDF]