title: Control-released hepatocyte growth factor prevents the progression of heart failure in stroke-prone spontaneously hypertensive rats.
abstract: BACKGROUND
  We have developed a hepatocyte growth factor (HGF)-incorporating gelatin hydrogel sheet (HGF sheet), which was designed to release HGF more than 2 weeks in vivo. The present study investigated whether the HGF sheet could prevent the progression of heart failure in stroke-prone spontaneously hypertensive rats.
  
  
  METHODS
  Stroke-prone spontaneously hypertensive rats at the age of 25 weeks received placement of an HGF sheet on the left ventricular free wall (HGF, n = 10) or sham-operation (control, n = 10). All animals were followed up with Doppler echocardiography during the next 4 weeks and then underwent histologic analysis. The influence of the hydrogel sheet alone was assessed by echocardiography and left ventricular pressure measurements. Survival study was performed (each group, n = 11) at the age of 30 weeks.
  
  
  RESULTS
  There were two deaths in the control group and no deaths in the HGF group during the 4 weeks. Fractional shortening was significantly higher, and left ventricular diastolic dimension was significantly smaller in the HGF than in the control group. The slope of the peak early diastolic filling velocity and the ratio of that slope to the slope of the peak filling velocity at atrial contraction were significantly lower in the HGF than the control group. Myocardial fibrosis was lower and capillary density was significantly higher in the HGF than the control group. Placement of the hydrogel sheet alone did not affect any cardiac function compared with sham operation. The survival rate at 10 weeks after the surgery was much higher in the HGF than the control group.
  
  
  CONCLUSIONS
  The HGF sheet improves cardiac function, reverses left ventricular remodeling, and markedly improves survival in spontaneously hypertensive rats. These beneficial effects are associated with angiogenesis and reduced fibrosis in the left ventricular myocardium.
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University, Graduate School of Medicine, Kyoto, Japan.
authors.forename: Genichi
authors.initials: G
authors.lastname: Sakaguchi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tambara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozeki
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Goditha
authors.initials: G
authors.lastname: Premaratne
authors.forename: Xue
authors.initials: X
authors.lastname: Lin
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Nishimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Komeda
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D018450:Disease Progression; D015150:Echocardiography, Doppler; D006333:Heart Failure / Q000503:physiopathology / Q000517:prevention & control*; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D003692:Delayed-Action Preparations; D017228:Hepatocyte Growth Factor