Successful transplantation of rat hearts subjected to extended cold preservation with a novel preservation solution

被引:16
|
作者
Wakayama, Kenji
Fukai, Moto [1 ]
Yamashita, Kenichiro
Kimura, Taichi [2 ]
Hirokata, Gentaro
Shibasaki, Susumu
Fukumori, Daisuke
Haga, Sanae [3 ]
Sugawara, Mitsuru [4 ]
Suzuki, Tomomi
Taniguchi, Masahiko
Shimamura, Tsuyoshi
Furukawa, Hiroyuki
Ozaki, Michitaka [3 ]
Kamiyama, Toshiya
Todo, Satoru
机构
[1] Hokkaido Univ, Grad Sch Med, Dept Gen Surg, Kita Ku, Sapporo, Hokkaido 0608638, Japan
[2] Hokkaido Univ, Grad Sch Med, Dept Pathol, Canc Res Lab, Sapporo, Hokkaido 0608638, Japan
[3] Hokkaido Univ, Grad Sch Med, Dept Mol Surg, Sapporo, Hokkaido 0608638, Japan
[4] Hokkaido Univ, Fac Pharmaceut Sci, Sapporo, Hokkaido 0608638, Japan
关键词
cold preservation; deuterium oxide; heart transplantation; preservation solution; rat; OF-WISCONSIN SOLUTION; HEAVY-WATER D2O; ISCHEMIA/REPERFUSION INJURY; ORGAN PRESERVATION; CELSIOR SOLUTION; CELL-DEATH; CALPAIN; DEUTERIUM; STORAGE; REPERFUSION;
D O I
10.1111/j.1432-2277.2012.01469.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
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 Ca2+ -dependent proteases activity were assessed in the 24-h preservation group. The cytosolic Ca2+ 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 Ca2+ overload during cold preservation. Dsol inhibited myocardial injury and improved graft survival by suppressing Ca2+ overload during the preservation and the activation of Ca2+ -dependent proteases. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.
引用
收藏
页码:696 / 706
页数:11
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