Granulocyte colony-stimulating factor and stem cell factor improve contractile reserve of the infarcted left ventricle independent of restoring muscle mass.

Abstract

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