Treatment with granulocyte-colony stimulating factor in patients with acute myocardial infarction. Evidence for a stimulation of neovascularization and improvement of myocardial perfusion.
BACKGROUND
Stem cell therapy has been suggested to be beneficial in patients after acute myocardial infarction (AMI). Strategies of treatment are either a local application of mononuclear bone marrow cells (BMCs) into the infarct-related artery or a systemic therapy with the granulocyte-stimulating factor (G-CSF) to mobilize BMCs. Nevertheless, the mechanisms responsible for improvement of cardiac function and perfusion are speculative at present. This study has been performed to investigate the effect of G-CSF on systemic levels of vascular growth factors and chemokines responsible for neovascularization, that might help to understand the positive effects of a G-CSF therapy after AMI.


RESULTS
Five patients in the treatment group and 5 patients in the control group were enrolled in this study. The patients in the treatment group received 10 microg/kg bodyweight/day of G-CSF subcutaneously for a mean treatment duration of 6.6 +/- 1.1 days. In both groups, levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and monocyte chemotactic protein-1 (MCP-1) were measured on day 2 to 3 and day 5 after AMI. The regional wall perfusion and the ejection fraction (EF) were evaluated before discharge and after 3 months with ECG-gated MIBI-SPECT and radionuclide ventriculography, respectively. Significant higher levels of VEGF (p < 0.01), bFGF (p < 0.05) and MCP-1 (p < 0.05) were found in the treatment group compared to the control group. Levels of VEGF and bFGF remained on a plateau during the G-CSF treatment and decreased significantly in the control group. The wall perfusion improved significantly within the treatment group and between the groups (p < 0.05), respectively. The EF improved significantly within the treatment group (p < 0.05), but the change of the EF between the groups was not significant.


CONCLUSIONS
In patients with AMI, the treatment with G-CSF modulates the formation of vascular growth factors that might improve neovascularization and result in an improved myocardial perfusion and function.
Kuethe
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Friedhelm Küthe, MD, Friedrich-Schiller-Universität Jena, Klinik für Innere Medizin I, Erlanger Allee 101, D-07740 Jena, Germany.
Krack
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A
Fritzenwanger
M
M
Herzau
M
M
Opfermann
T
T
Pachmann
K
K
Sayer
H G
HG
Werner
G S
GS
Gottschild
D
D
Figulla
H R
HR
D000208:Acute Disease; D000368:Aged; D018932:Chemokine CCL2 / Q000097:blood; D018925:Chemokines / Q000096:biosynthesis; D003326:Coronary Circulation / Q000187:drug effects*; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011446:Prospective Studies; D015635:Radionuclide Ventriculography; D019275:Radiopharmaceuticals; D013318:Stroke Volume / Q000502:physiology; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D018932:Chemokine CCL2; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016179:Granulocyte Colony-Stimulating Factor; D017256:Technetium Tc 99m Sestamibi