Basic Research in Cardiology

, Volume 106, Issue 6, pp 995–1008

G-CSF therapy reduces myocardial repolarization reserve in the presence of increased arteriogenesis, angiogenesis and connexin 43 expression in an experimental model of pacing-induced heart failure

  • Peter Milberg
  • Rainer Klocke
  • Gerrit Frommeyer
  • Trong Hung Quang
  • Kati Dieks
  • Jörg Stypmann
  • Nani Osada
  • Michael Kuhlmann
  • Michael Fehr
  • Hendrik Milting
  • Sigrid Nikol
  • Johannes Waltenberger
  • Günter Breithardt
  • Lars Eckardt
Original Contribution

DOI: 10.1007/s00395-011-0230-8

Cite this article as:
Milberg, P., Klocke, R., Frommeyer, G. et al. Basic Res Cardiol (2011) 106: 995. doi:10.1007/s00395-011-0230-8

Abstract

G-CSF (granulocyte colony-stimulating factor) treatment has been shown to cause beneficial effects including a reduction of inducible arrhythmias in rodent models of ischemic cardiomyopathy. The aim of the present study was to test whether these effects do also apply to pacing-induced non-ischemic heart failure. In 24 female rabbits, heart failure was induced by rapid ventricular pacing. 24 rabbits were sham operated. The paced rabbits developed a significant decrease of ejection fraction. 11 heart failure rabbits (CHF) and 11 sham-operated (S) rabbits served as controls, whereas 13 sham (S-G-CSF) and 13 heart failure rabbits (CHF-G-CSF) were treated with 10 μg/kg G-CSF s.c. over 17 ± 4 days. G-CSF treatment caused a ~25% increased arterial and capillary density and a ~60% increased connexin 43 expression in failing hearts. In isolated, Langendorff-perfused rabbit hearts eight monophasic action potential recordings showed prolongation of repolarization in CHF as compared with controls in the presence of the QT prolonging agent erythromycin (+33 ± 12 ms; p < 0.01). Moreover, a significant increase in dispersion of repolarization contributed to a significantly higher rate of ventricular tachyarrhythmias in CHF. G-CSF-pre-treated hearts showed a further increase in prolongation of repolarization as compared with S and CHF. The further increase in dispersion of repolarization [S-G-CSF: +23 ± 9 ms (spatial), +13 ± 7 ms (temporal); CHF-G-CSF: +38 ± 14 ms (spatial), +10 ± 4 ms (temporal); p < 0.05 as compared with S and CHF], increased the incidence of ventricular tachyarrhythmias. In summary, chronic G-CSF treatment has moderate beneficial effects on parameters potentially related to hemodynamic function in the non-ischemic rabbit CHF model. However, a significant reduction of repolarization reserve might seriously challenge its suitability as a therapeutic agent for chronic CHF therapy.

Keywords

G-CSF therapy Chronic heart failure Repolarization reserve Dispersion of repolarization Ventricular tachyarrhythmia 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Peter Milberg
    • 1
    • 7
  • Rainer Klocke
    • 6
  • Gerrit Frommeyer
    • 1
  • Trong Hung Quang
    • 6
  • Kati Dieks
    • 1
  • Jörg Stypmann
    • 2
    • 6
  • Nani Osada
    • 3
  • Michael Kuhlmann
    • 6
  • Michael Fehr
    • 4
  • Hendrik Milting
    • 5
  • Sigrid Nikol
    • 6
  • Johannes Waltenberger
    • 6
  • Günter Breithardt
    • 1
  • Lars Eckardt
    • 1
  1. 1.Division of Clinical and Experimental Electrophysiology, Department of Cardiology and AngiologyHospital of the Westfälische Wilhelms-UniversityMünsterGermany
  2. 2.Interdisciplinary Centre for Clinical Research, Central Project Group (ZPG 4a)Westfälische Wilhelms-UniversityMünsterGermany
  3. 3.Department of Medical Informatics and BiomathematicsUniversity of MünsterMünsterGermany
  4. 4.Stiftung Tierärztliche Hochschule HannoverHannoverGermany
  5. 5.Heart and Diabetes CenterBad OeynhausenGermany
  6. 6.Division and Clinic of Cardiology, Department of Cardiology and AngiologyHospital of the Westfälische Wilhelms-UniversityMünsterGermany
  7. 7.Department für Kardiologie und Angiologie, Abteilung für RhythmologieUniversitätsklinikum MünsterMünsterGermany

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