Intramyocardial injection of fibroblast growth factor-2 plus heparin suppresses cardiac failure progression in rats with hypertensive heart disease.
A reduction of coronary flow reserve has been reported in patients with hypertensive heart disease (HHD), which suggests that myocardial ischemia may contribute to the progression to cardiac failure in HHD. Therefore, we evaluated whether fibroblast growth factor (FGF)-2 and/or heparin, which induce angiogenesis, may affect cardiac function in the setting of HHD. We used Dahl salt sensitive (DS) rats as an HHD model. Direct intramyocardial injection of 100 microg of FGF-2 plus 1.28 microg of heparin (n = 6), 100 microg of FGF-2 (n = 6), 1.28 microg of heparin (n = 6) or saline (n = 6) were performed in 9-week-old rats. Echocardiography was performed to evaluate cardiac function at 9, 11, and 13 weeks of age. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations were measured at 8 and 13 weeks of age. DS rats were killed 4 weeks after myocardial injection (at 13 weeks of age), and myocardial capillary density was assessed by von Willebrand factor staining. Injection of FGF-2 plus heparin significantly decreased left ventricular end-diastolic diameter (P < 0.0001) and left ventricular end-systolic diameter (P < 0.0001), significantly improved the reduction of left ventricular fractional shortening (P = 0.0005), significantly decreased plasma ANP (P < 0.0001) and BNP (P = 0.016) concentrations, and significantly increased myocardial capillary density (P = 0.0002) compared with injection of saline. These findings indicate that intramyocardial injection of FGF-2 plus heparin suppresses the progression of cardiac failure in DS rats. FGF-2 plus heparin administration may be a new therapeutic strategy for the treatment of HHD.
Yajima
Suguru
S
Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University School of Medicine, Ohashi Hospital, Tokyo, Japan.
Ishikawa
Michiro
M
Kubota
Tetsuya
T
Moroi
Masao
M
Sugi
Kaoru
K
Namiki
Atsushi
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure; D001835:Body Weight; D004452:Echocardiography; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D007267:Injections; D008297:Male; D009206:Myocardium; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009389:Neovascularization, Pathologic / Q000473:pathology; D051381:Rats; D020303:Rats, Inbred Dahl; D016276:Ventricular Function
D016222:Fibroblast Growth Factor 2; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006493:Heparin