Granulocyte Colony-Stimulating Factor and Stem Cell Factor Improve Contractile Reserve of the Infarcted Left Ventricle Independent of Restoring Muscle Mass

J Am Coll Cardiol. 2005 Nov 1;46(9):1662-9. doi: 10.1016/j.jacc.2005.08.012.

Abstract

Objectives: We investigated whether granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) could promote myocardial regeneration after coronary artery occlusion and improve left ventricular (LV) function.

Background: Cytokine-induced mobilization of bone marrow stem cells in the heart may represent a promising strategy for replacing infarcted myocardium.

Methods: Sprague-Dawley rats were subjected to permanent coronary occlusion. A treated group (n = 19) received G-CSF (100 microg/kg) and SCF (25 microg/kg) subcutaneously, starting 2 h after surgery and continuing daily for an additional 4 days. Control rats (n = 21) received sterile water. The peripheral blood content in hematopoietic progenitor cells was analyzed.

Results: At eight weeks, LV angiograms (rest and dobutamine stress) and histologic analysis were performed. At rest, LV ejection fraction (LVEF) was 0.45 in controls and 0.52 in treated hearts (p = 0.16). For any infarct size, LVEF was greater in the treated group (p = 0.045). Under dobutamine stress, treated animals had smaller LV end-diastolic and -systolic volumes (0.37 +/- 0.04 ml and 0.16 +/- 0.03 ml) versus control animals (0.51 +/- 0.05 ml and 0.26 +/- 0.04 ml; p = 0.026 and 0.048) with a 7% improvement in ejection fraction. Scar thickness was 1.1 +/- 0.1 mm in treated hearts and 1.0 +/- 0.1 mm in controls (p = 0.36). Scar morphology was similar in both groups without obvious new muscle in the scar.

Conclusions: Because we did not find evidence of new muscle cells in the infarct area, our conclusion is that G-CSF and SCF enhanced the LV functional reserve of the heart without replacing scar tissue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Myocardial Contraction
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Factor / therapeutic use*
  • Ventricular Function, Left*

Substances

  • Stem Cell Factor
  • Granulocyte Colony-Stimulating Factor