title: Reduction of chronic graft injury with a new HTK-based preservation solution in a murine heart transplantation model.
abstract: 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.
  
  
  METHODS
  Hearts of C57BL/6J (H-2b) mice were stored for 15 h in 0-4 °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-β expression). The transplanted hearts were evaluated histologically for myocardial damage, vasculopathy and interstitial fibrosis. TGF-β expression was assessed immunohistologically. All investigators were blinded to the groups. ANOVA and LSD post hoc test were used for statistical analysis.
  
  
  RESULTS
  The re-beating time was significantly shorter in hearts stored in the new solution (10.3±2.6 min vs. HTK 14.2±4.1 min; p<0.05). The palpation score was significantly higher in hearts stored in the new solution (2.3±0.4 vs. HTK 1.6±0.5; p<0.01). Hearts stored in the new solution showed a lower myocardial injury score (1.8±0.2 vs. HTK 2.2±0.7), less interstitial fibrosis (4.8±1.9% vs. HTK 8.5±3.8%, p<0.05), less vasculopathy (14.7±6.9% vs. 22.0±23.2%; p=0.06) and lower TGF-β1-expression (6.6±1.4% vs. HTK 12.0±4.6%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Türk
authors.forename: Song
authors.initials: S
authors.lastname: Su
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauen
authors.forename: Thorsten
authors.initials: T
authors.lastname: Feldkamp
authors.forename: Herbert
authors.initials: H
authors.lastname: de Groot
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D050377:Cold Ischemia / Q000379:methods*; D004719:Endomyocardial Fibrosis / Q000517:prevention & control; D005998:Glycine / Q000737:chemistry; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D016027:Heart Transplantation / Q000379:methods*; D006639:Histidine / Q000737:chemistry; D007656:Ketoglutaric Acids / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D016042:Transplantation, Heterotopic; D014185:Transplantation, Isogeneic; D014364:Tryptophan / Q000737:chemistry
chemical_list: D007656:Ketoglutaric Acids; D019188:Organ Preservation Solutions; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006639:Histidine; D014364:Tryptophan; D000409:Alanine; D005998:Glycine