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Ann Thorac Surg 2005;79:1627-1634
© 2005 The Society of Thoracic Surgeons

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Original articles: Cardiovascular

Control-Released Hepatocyte Growth Factor Prevents the Progression of Heart Failure in Stroke-Prone Spontaneously Hypertensive Rats

^a Department of Cardiovascular Surgery, Kyoto University, Graduate School of Medicine, Kyoto, Japan
^b Department of Frontier Medical Science, Kyoto University, Kyoto, Japan
^c Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan

Accepted for publication October 20, 2004.

^_* Address reprint requests to Dr Komeda, Graduate School of Medicine, Dept of Cardiovascular Surgery, Kyoto University, 54 Kawahara-cho Shogoin Sakyo-ku, Kyoto, 606–8507, Japan (E-mail: masakom{at}kuhp.kyoto-u.ac.jp).

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.

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