Chronic inborn erythrocytosis leads to cardiac dysfunction and premature death in mice overexpressing erythropoietin

The most common cause of an increase of the hematocrit is secondary to elev ated erythropoietin levels. Erythrocytosis is assumed to cause higher blood viscosity that could put the cardiovascular system at hemodynamic and rheo logical risks. Secondary erythrocytosis results from tissue hypoxia, and on e can hardly define what cardiovascular consequences are caused by chronic erythrocytosis or hypoxia, Herein, a novel transgenic (tg) mouse line is ch aracterized that is erythrocytotic because of chronic over-expression of th e 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 inc reased by 75%, Unexpectedly, blood pressure was not elevated and cardiac ou tput was not decreased. Still, the adult tg mice showed features of cardiac dysfunction with increased heart weight. In vivo, high-frequency echocardi ography revealed marked ventricular dilatation that was confirmed by histol ogic examination. Furthermore, by transmission electron microscopy, a promi nent intracellular edema of the cardiomyocytes was seen. Exercise performan ce of the tg mice was dramatically reduced, unmasking the severity of their compromised cardiovascular function, in addition, life expectancy of the t g mice was significantly reduced to 7.4 months. Our findings suggest that s evere erythrocytosis per se results in cardiac dysfunction and markedly red uced life span, (C) 2001 by The American Society of Hematology.