Skip Navigation

Cardiovascular Research 2004 61(1):105-114; doi:10.1016/j.cardiores.2003.10.026
© 2004 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Deten, A.
Right arrow Articles by Zimmer, H.-G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Deten, A.
Right arrow Articles by Zimmer, H.-G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2004, European Society of Cardiology

Norepinephrine-induced acute heart failure in transgenic mice overexpressing erythropoietin

Alexander Deten*,a, Junpei Shibatab, Dimitri Scholzc, Wilfried Briesta, Klaus F Wagnerb, Roland H Wengera and Heinz-Gerd Zimmera

aCarl-Ludwig-Institute of Physiology, Leipzig University, Liebigstraße 27, D-04103 Leipzig, Germany
bDepartment of Anesthesiology, Lübeck University, Ratzeburger Allee 160, D-23538 Lübeck, Germany
cDepartment of Experimental Cardiology, Max-Planck-Institute, Benekestraße 2, D-61231 Bad Nauheim, Germany

* Corresponding author. Tel.: +49-341-971-5500; fax: +49-341-971-5509. deta{at}medizin.uni-leipzig.de

Objective: Overexpression of erythropoietin (Epo) in mice (Epo-tg6) leads to an increase in hematocrit and blood volume, and strongly reduces endurance upon exercise. It was the aim of this study to characterize the mechanisms underlying the reduced cardiac performance. Methods: Left (LV) and right (RV) ventricular function was measured with and without norepinephrine (NE) stimulation in 12 anaesthetized Epo-tg6 and in 13 wild-type (WT) control mice. Results: There were no differences in heart function under baseline resting conditions. Stimulation with NE (10 µl bolus injections of 1–100 ng per mouse) in WT mice led to a dose-dependent increase in heart rate (HR), LV developed pressure (LVDP) and rate of rise in LV pressure (LV dP/dtmax), while LV end-diastolic pressure (LVEDP) was unchanged. Except for HR, these parameters increased to a lesser extent in EPO-tg6 mice. Strikingly, LVEDP strongly increased in Epo-tg6 mice after NE (up to >20 mmHg). Eleven out of 13 Epo-tg6, but none of the WT mice died or required resuscitation after high-doses of NE. In these cases severe diastolic dysfunction became overt since the relative myocardial relaxation time was significantly prolonged and the duration of diastole was shortened. Moreover, the ECG showed a marked ST segment depression as well as deep negative T-waves. The NE-induced reduction in myocardial adenosin-triphosphate (ATP) content was more pronounced in Epo-tg6 mice after 10 min of continuous NE infusion (50 ng/min per mouse). Conclusion: NE-induced stress in Epo-tg6 mice led to acute heart failure associated with diastolic dysfunction and myocardial ischemia.

KEYWORDS Adrenergic agonists; Heart failure; Ischemia

Time for primary review 24 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.