title: Successful transplantation of rat hearts subjected to extended cold preservation with a novel preservation solution.
abstract: Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation. Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. In addition to graft survival, myocardial injury, ATP content, and Ca(2+) -dependent proteases activity were assessed in the 24-h preservation group. The cytosolic Ca(2+) concentration of H9c2 cardiomyocytes after 24-h cold preservation was assessed. Dsol significantly improved 7-day graft survival after 36-h preservation. After 24-h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase-3 after reperfusion. Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day. Dsol significantly inhibited Ca(2+) overload during cold preservation. Dsol inhibited myocardial injury and improved graft survival by suppressing Ca(2+) overload during the preservation and the activation of Ca(2+) -dependent proteases. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.
authors.affiliation: Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakayama
authors.forename: Moto
authors.initials: M
authors.lastname: Fukai
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yamashita
authors.forename: Taichi
authors.initials: T
authors.lastname: Kimura
authors.forename: Gentaro
authors.initials: G
authors.lastname: Hirokata
authors.forename: Susumu
authors.initials: S
authors.lastname: Shibasaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukumori
authors.forename: Sanae
authors.initials: S
authors.lastname: Haga
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sugawara
authors.forename: Tomomi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kamiyama
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
mesh_terms: D000241:Adenosine; D000255:Adenosine Triphosphate / Q000378:metabolism; D000493:Allopurinol; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D015925:Cryopreservation / Q000379:methods*; D017666:Deuterium Oxide; D005978:Glutathione; D006085:Graft Survival / Q000502:physiology*; D016027:Heart Transplantation; D007328:Insulin; D053208:Kaplan-Meier Estimate; D008297:Male; D008353:Mannitol; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D011917:Rats, Inbred Lew; D013395:Sucrose
chemical_list: D015415:Biomarkers; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D008353:Mannitol; D013395:Sucrose; D000493:Allopurinol; D000255:Adenosine Triphosphate; D002154:Calpain; D053148:Caspase 3; D005978:Glutathione; D017666:Deuterium Oxide; D000241:Adenosine; D011887:Raffinose; D002118:Calcium