Reduction of chronic graft injury with a new HTK-based preservation solution in a murine heart transplantation model

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• 作者：Tobias R. T&uuml ; rk^a ; ^b ; ¹ ; Song Su^a ; ^c ; ¹ ; Ursula Rauen^d ; Thorsten Feldkamp^a ; Herbert de Groot^d ; Andreas Kribben^a ; Oliver Witzke^a ; ^{oliver.witzke@uk-essen.de}
• 关键词：Glycine ; Ischemia-reperfusion ; N-acetyl-l-histidine ; Preservation injury ; Alanine ; Vasculopathy
• 刊名：Cryobiology
• 出版年：2012
• 期刊代码：166_00112240
• 类别：bio
• 出版时间：June, 2012
• 卷：64
• 期：3
• 页码：273-278
• 文件大小：758 K

摘要

lass="h4">Objective

Aim of this study was to evaluate a new histidine-tryptophan-ketoglutarate (HTK)-based preservation solution on chronic isograft injury in comparison to traditional HTK solution.

lass="h4">Methods

Hearts of C57BL/6J (H-2b) mice were stored for 15 h in 0-4 掳C cold preservation solution and then transplanted heterotopically into C57BL/6J (H-2b) mice. Three groups were evaluated: HTK, the base solution of a new preservation solution and hearts without cold ischemia (control). Time to restoration of heartbeat was measured (re-beating time). Strength of the heartbeat was palpated daily and scored on a 4-level scale (palpation score). Animals were sacrificed after 60 days of observation (24 h for TGF-尾 expression). The transplanted hearts were evaluated histologically for myocardial damage, vasculopathy and interstitial fibrosis. TGF-尾 expression was assessed immunohistologically. All investigators were blinded to the groups. ANOVA and LSD post hoc test were used for statistical analysis.

lass="h4">Results

The re-beating time was significantly shorter in hearts stored in the new solution (10.3 卤 2.6 min vs. HTK 14.2 卤 4.1 min; p < 0.05). The palpation score was significantly higher in hearts stored in the new solution (2.3 卤 0.4 vs. HTK 1.6 卤 0.5; p < 0.01). Hearts stored in the new solution showed a lower myocardial injury score (1.8 卤 0.2 vs. HTK 2.2 卤 0.7), less interstitial fibrosis (4.8 卤 1.9%vs. HTK 8.5 卤 3.8%, p < 0.05), less vasculopathy (14.7 卤 6.9%vs. 22.0 卤 23.2%; p = 0.06) and lower TGF-尾1-expression (6.6 卤 1.4%vs. HTK 12.0 卤 4.6%).

lass="h4">Conclusion

The new HTK-based solution reduces the chronic isograft injury. This protective effect is likely achieved through several modifications and supplements into the new solution like N-acetyl-l-histidine, glycine, alanine, arginine and sucrose.