title: Myocardial protective effect of human recombinant hepatocyte growth factor for prolonged heart graft preservation in rats.
abstract: BACKGROUND
  In heart transplantation, myocardial apoptosis during hypothermic storage contributes to graft dysfunction. On the other hand, hepatocyte growth factor (HGF) has been reported to be an antiapoptotic factor in the heart. Therefore, we assessed whether the administration of recombinant human HGF (rh-HGF) prevents apoptosis in the prolonged preserved myocardium, resulting in an improvement in the cardiac function of the graft.
  
  
  METHODS
  Isolated rat hearts were subjected to 4 hr (group A), 6 hr (group B), and 8 hr (group C: without rh-HGF vs. group D: with 100 microg of rh-HGF) of hypothermic storage followed by 60 min of normothermic reperfusion (n=5 in each group).
  
  
  RESULTS
  Compared with non-HGF-treated hearts (group C), HGF-treated hearts (group D) showed a significantly higher recovery rate of left ventricular developed pressure (38+/-5% vs. 58+/-6%, P<0.01) and maximum dp/dt (53+/-7% vs. 74+/-4%, P<0.01) and a lower rate of TUNEL-positive cardiomyocytes (7.8+/-6.0% vs. 25.3+/-8.9%, P<0.05) after 60 min of reperfusion. Western blot analysis revealed that c-Met/HGF receptor expression was stronger in the HGF-treated myocardium than in the non-HGF-treated myocardium after 8 hr of storage and was associated with a weaker expression of caspase-3 and a stronger expression of Bcl-xL after 60 min of reperfusion.
  
  
  CONCLUSIONS
  The administration of rh-HGF before storage improved cardiac function after prolonged myocardial preservation by preventing apoptosis through the c-Met/HGF receptor. Thus, the addition of rh-HGF in the storage solution may be a promising strategy for prolonged heart graft preservation.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ryugo
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ono
authors.forename: Norihide
authors.initials: N
authors.lastname: Fukushima
authors.forename: Alexey N
authors.initials: AN
authors.lastname: Aleshin
authors.forename: Shinya
authors.initials: S
authors.lastname: Mizuno
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015925:Cryopreservation; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D009926:Organ Preservation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology*; D020127:Recovery of Function; D013194:Staining and Labeling; D013997:Time Factors; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051020:bcl-X Protein; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases