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      Blockade of Renin-Angiotensin System Reduces QT Dispersion and Improves Intracellular Ca/Mg Status in Hemodialysis Patients


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          Background: Electrolyte impairments are common in hemodialysis (HD) patients. Consequently, QT dispersion (QTd) is prolonged, correlating with high intracellular magnesium. In patients with cardiac disorders, renin-angiotensin system (RAS) inhibition reduces QTd. Aim: To compare the effects of ACE inhibition or AT-1 blockade on QTd duration and intracellular magnesium (Mg)/calcium (Ca) in peripheral blood mononuclear cells (PBMC) from chronic HD patients. Methods: 24 HD patients received cilazapril for 8 weeks and, following a 2-week withdrawal, were switched to valsartan for additional 8 weeks. QTd measurements and PBMC isolation were performed at the beginning and the end of each period. Total intracellular Ca and Mg were assessed by atomic spectrometer, and cytosolic free Ca<sup>2+</sup> by fluorocytometer. Results: Both treatments significantly decreased QTd, demonstrating similar reduction magnitudes. In both groups, PBMC exhibited basally low cytosolic Ca<sup>2+</sup> and undisturbed high transmembrane Ca<sup>2+</sup> influx following phytohemagglutinin stimulation. Total intracellular Ca was increased, while Mg was reduced, following either treatment. The total intracellular Ca/Mg ratio inversely correlated with QTd duration. Conclusions: (1) RAS inhibition reduces prolonged QTd in HD patients. (2) In PBMC from ordinarily Ca-depleted HD patients, RAS suppression brings about elevation of total intracellular Ca. (3) RAS blockade decreases high intracellular Mg in PBMC from HD patients. Consequently, the Ca/Mg ratio increases, inversely correlating with QTd reduction.

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          Most cited references26

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          Measurement, interpretation and clinical potential of QT dispersion.

          QT dispersion was originally proposed to measure spatial dispersion of ventricular recovery times. Later, it was shown that QT dispersion does not directly reflect the dispersion of recovery times and that it results mainly from variations in the T loop morphology and the error of QT measurement. The reliability of both automatic and manual measurement of QT dispersion is low and significantly lower than that of the QT interval. The measurement error is of the order of the differences between different patient groups. The agreement between automatic and manual measurement is poor. There is little to choose between various QT dispersion indices, as well as between different lead systems for their measurement. Reported values of QT dispersion vary widely, e.g., normal values from 10 to 71 ms. Although QT dispersion is increased in cardiac patients compared with healthy subjects and prognostic value of QT dispersion has been reported, values are largely overlapping, both between healthy subjects and cardiac patients and between patients with and without adverse outcome. In reality, QT dispersion is a crude and approximate measure of abnormality of the complete course of repolarization. Probably only grossly abnormal values (e.g. > or =100 ms), outside the range of measurement error may potentially have practical value by pointing to a grossly abnormal repolarization. Efforts should be directed toward established as well as new methods for assessment and quantification of repolarization abnormalities, such as principal component analysis of the T wave, T loop descriptors, and T wave morphology and wavefront direction descriptors.
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            The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens.

            To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.
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              ACE inhibitors and survival of hemodialysis patients.

              Cardiovascular disease is a leading cause of death in patients with end-stage renal disease (ESRD). Hypertension is a major risk factor for cardiovascular complications in these patients. Angiotensin-converting enzyme (ACE) inhibitors are an effective treatment for hypertension in patients with ESRD and are known to improve prognosis in patients with chronic renal failure. We investigated their effect on mortality in patients undergoing long-term hemodialysis therapy. Clinical data for patients on hemodialysis therapy between 1994 and 2000 were reviewed. Patients were grouped according to whether they had been treated with ACE inhibitors. Sixty patients had been treated with ACE inhibitors (treated group) and 66 patients had not (untreated group). Blood pressure reduction was not significantly different between the treated and untreated groups. Nevertheless, comparing the treated group with the untreated group, mortality was decreased significantly in the treated group, with a risk reduction of 52% (rate ratio [RR], 0.482; confidence interval [CI], 0.25 to 0.91; P < 0.0019). In treated patients 65 years or younger, the absolute risk reduction of mortality was 79% (RR, 0.211; CI, 0.08 to 0.58; P < 0.0006). Although further research is needed, these preliminary findings suggest that ACE inhibitors, independently of their antihypertensive effect, may dramatically reduce mortality among chronic hemodialysis patients 65 years or younger. Copyright 2002 by the National Kidney Foundation, Inc.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                November 2006
                25 September 2006
                : 104
                : 4
                : c176-c184
                Nephrology Division, Assaf Harofeh Medical Center, Affiliated to Sackler Medical School, Tel Aviv University, Zerifin, Israel
                95853 Nephron Clin Pract 2006;104:c176–c184
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                : 11 January 2006
                : 25 July 2006
                Page count
                Figures: 4, Tables: 3, References: 40, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/95853
                Self URI (text/html): https://www.karger.com/Article/FullText/95853
                Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
                Original Paper

                Cardiovascular Medicine,Nephrology
                Intracellular Ca/Mg,Hemodialysis,QT dispersion,Renin-angiotensin system,ACE inhibitors


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