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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wagner, K. F. Articles by Fandrey, J. Search for Related Content PubMed PubMed Citation Articles by Wagner, K. F. Articles by Fandrey, J. Related Collections Hematopoiesis and Stem Cells Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 January 2001, Vol. 97, No. 2, pp. 536-542 RED CELLS Chronic inborn erythrocytosis leads to cardiac dysfunction and premature death in mice overexpressing erythropoietin Klaus F. Wagner, Dörthe M. Katschinski, Jo Hasegawa, Dunja Schumacher, Birgit Meller, Ulrich Gembruch, Uda Schramm, Wolfgang Jelkmann, Max Gassmann, and Joachim Fandrey From the Department of Anesthesiology, the Institute of Physiology, the Department of Radiotherapy and Nuclear Medicine, the Department of Gynecology and Obstetrics, and the Institute of Anatomy, Medical University of Lübeck, Lübeck, Germany; the Institute of Physiology, University of Zürich, Switzerland; and the Institute of Physiology, University of Essen, Essen, Germany. The most common cause of an increase of the hematocrit is secondary to elevated erythropoietin levels. Erythrocytosis is assumed to cause higher blood viscosity that could put the cardiovascular system at hemodynamic and rheological risks. Secondary erythrocytosis results from tissue hypoxia, and one can hardly define what cardiovascular consequences are caused by chronic erythrocytosis or hypoxia. Herein, a novel transgenic (tg) mouse line is characterized that is erythrocytotic because of chronic overexpression of the human erythropoietin gene. These mice grow up well, reaching a hematocrit of about 0.80 in adulthood. Blood volume of adult tg mice was markedly increased by 75%. Unexpectedly, blood pressure was not elevated and cardiac output was not decreased. Still, the adult tg mice showed features of cardiac dysfunction with increased heart weight. In vivo, high-frequency echocardiography revealed marked ventricular dilatation that was confirmed by histologic examination. Furthermore, by transmission electron microscopy, a prominent intracellular edema of the cardiomyocytes was seen. Exercise performance of the tg mice was dramatically reduced, unmasking the severity of their compromised cardiovascular function. In addition, life expectancy of the tg mice was significantly reduced to 7.4 months. Our findings suggest that severe erythrocytosis per se results in cardiac dysfunction and markedly reduced life span. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. van Rooijen, E. E. Voest, I. Logister, J. Korving, T. Schwerte, S. Schulte-Merker, R. H. Giles, and F. J. van Eeden Zebrafish mutants in the von Hippel-Lindau tumor suppressor display a hypoxic response and recapitulate key aspects of Chuvash polycythemia Blood, June 18, 2009; 113(25): 6449 - 6460. [Abstract] [Full Text] [PDF] J. Soliz, J. J. Thomsen, C. Soulage, C. Lundby, and M. Gassmann Sex-dependent regulation of hypoxic ventilation in mice and humans is mediated by erythropoietin Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2009; 296(6): R1837 - R1846. [Abstract] [Full Text] [PDF] M. Gassmann, A. Manini, T. Stallmach, B. Saam, G. Kuhn, B. Grenacher, A. Y. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020