Therapeutic angiogenesis induced by injecting hepatocyte growth factor in ischemic canine hearts.
OBJECTIVE
Therapeutic angiogenesis, induced by the direct injection of angiogenic growth factors or by transmyocardial laser revascularization (TMLR), has shown great potential as a new therapeutic strategy for end-stage coronary artery disease. However, no significant differences in angiogenic effects of TMLR and vascular endothelial growth factor (VEGF) have been reported. We compared the effects of the intramyocardial injection of hepatocyte growth factor (HGF), a novel angiogenic factor, with those of TMLR, by evaluating the improvement in regional blood flow and regional function in a canine heart model of chronic ischemia.


METHODS
To create a model of chronic ischemia, we ligated the left anterior descending artery (LAD) in 15 beagles. We divided the dogs into three groups according to the treatment given 1 month after ligation. Four dogs were given an intracardial injection of human recombinant HGF (H group), six dogs were given TMLR (T group), and five dogs were used as a control (C group). We compared the degree of improvement in regional blood flow and regional function 1 month after the treatment.


RESULTS
The regional myocardial blood flow and function were significantly better in the H group than in the T or C groups (P < 0.05). Histologically, there were significantly more von Willebrand factor-positive cells in the LAD region in the H group than in the T or C groups.


CONCLUSIONS
The intramural injection of recombinant human HGF resulted in therapeutic angiogenesis with an intrinsic contractile state, and it may have greater advantages than TMLR for the treatment of chronic ischemic heart disease.
Yamaguchi
Takahiro
T
First Department of Surgery, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Sawa
Yoshiki
Y
Miyamoto
Yuji
Y
Takahashi
Toshiki
T
Jau
Chung Chung
CC
Ahmet
Ismayil
I
Nakamura
Toshikazu
T
Matsuda
Hikaru
H
D000818:Animals; D001707:Biopsy, Needle; D003326:Coronary Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D004285:Dogs; D006334:Heart Function Tests; D006439:Hemodynamics / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011336:Probability; D020127:Recovery of Function; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D017228:Hepatocyte Growth Factor