Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-06, Vol.109 (21), p.2572-2580
• Main Authors: MINATOGUCHI, Shinya, TAKEMURA, Genzou, GOTO, Kazuko, KOMADA, Ai, TAKAHASHI, Tomoyuki, KOSAI, Kenichiro, FUJIWARA, Takako, FUJIWARA, Hisayoshi, CHEN, Xue-Hai, NINGYUAN WANG, UNO, Yoshihiro, KODA, Masahiko, ARAI, Masazumi, MISAO, Yu, CHUANJIANG LU, SUZUKI, Koji
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Cell Size - drug effects; Cicatrix - etiology; Cicatrix - pathology; Cicatrix - prevention & control; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Evaluation, Preclinical; Echocardiography; Granulation Tissue - pathology; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte Colony-Stimulating Factor - therapeutic use; Heart; Heart - drug effects; Macrophages - physiology; Matrix Metalloproteinase 1 - analysis; Matrix Metalloproteinase 9 - analysis; Medical sciences; Microscopy, Confocal; Miscellaneous; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardium - enzymology; Myocardium - pathology; Myocytes, Cardiac - drug effects; Pharmacology. Drug treatments; Rabbits; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Regeneration - drug effects; Ventricular Remodeling - drug effects
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000129770.93985.3E

We investigated whether the improvement of cardiac function and remodeling after myocardial infarction (MI) by granulocyte colony-stimulating factor (G-CSF) relates to acceleration of the healing process, in addition to myocardial regeneration. In a 30-minute coronary occlusion and reperfusion rabbit model, saline (S) or 10 microg x kg(-1) x d(-1) of human recombinant G-CSF (G) was injected subcutaneously from 1 to 5 days after MI. Smaller left ventricular (LV) dimension, increased LV ejection fraction, and thicker infarct-LV wall were seen in G at 3 months after MI. At 2, 7, and 14 days and 3 months after MI, necrotic tissue areas were 14.2+/-1.5/13.4+/-1.1, 0.4+/-0.1/1.8+/-0.5*, 0/0, and 0/0 mm2 x slice(-1) x kg(-1), granulation areas 0/0, 4.0+/-0.7/8.5+/-1.0*, 3.9+/-0.8/5.7+/-0.7,* and 0/0 mm2 x slice(-1) x kg(-1), and scar areas 0/0, 0/0, 0/0, and 4.2+/-0.5/7.9+/-0.9* mm2 x slice(-1) x kg(-1) in G and S, respectively (*P