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

• Published in: Journal of the American College of Cardiology 2010-02, Vol.55 (5), p.454-459
• Main Authors: Meyer, Christian, MD, Heiss, Christian, MD, Drexhage, Christine, MSc, Kehmeier, Eva S., MD, Balzer, Jan, MD, Mühlfeld, Anja, MD, Merx, Marc W., MD, Lauer, Thomas, MD, Kühl, Harald, MD, Floege, Jürgen, MD, Kelm, Malte, MD, Rassaf, Tienush, MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological activity; Biological and medical sciences; Body mass index; Brachial Artery - physiopathology; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Cardiovascular Diseases - etiology; Cholesterol; Dehydrogenases; Electrodes; Emergency and intensive care: renal failure. Dialysis management; endothelial function; Endothelium; Endothelium, Vascular - physiopathology; Enzymes; Female; Free radicals; Glycerol; hemodialysis; Hemoglobins - metabolism; Hemolysis; Humans; Intensive care medicine; Internal Medicine; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - physiopathology; Kidney Failure, Chronic - therapy; Male; Medical sciences; Middle Aged; nitric oxide; Nitric Oxide - blood; Patients; Potassium; Proteins; Renal Dialysis - adverse effects; Vasodilation
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2009.07.068

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 )