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Updated: May 24, 2026
Blood Circuit Reconstruction in an Abdominal Mouse Heart Transplantation Model
Published on: June 3, 2021
Reduction of chronic graft injury with a new HTK-based preservation solution in a murine heart transplantation model
Tobias R Türk1, Song Su, Ursula Rauen
1Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Germany.
Insights
A novel histidine-tryptophan-ketoglutarate (HTK)-based solution significantly reduces chronic isograft injury in heart transplantation compared to traditional HTK. This new solution enhances graft survival and function by minimizing myocardial damage and fibrosis.
Area of Science:
- Transplantation immunology
- Cardiovascular research
- Organ preservation
Background:
- Chronic isograft injury remains a significant challenge in heart transplantation.
- Traditional histidine-tryptophan-ketoglutarate (HTK) solution is widely used for organ preservation.
- Optimizing preservation solutions is crucial for improving long-term graft outcomes.
Purpose of the Study:
- To evaluate a new HTK-based preservation solution.
- To compare its efficacy against the traditional HTK solution in reducing chronic isograft injury.
- To assess the impact on myocardial damage, vasculopathy, and fibrosis.
Main Methods:
- Hearts from C57BL/6J mice were stored for 15 hours at 4°C in either the new HTK-based solution, traditional HTK, or without cold storage (control).
- Heterotopic heart transplantation was performed, and graft function was assessed by re-beating time and daily palpation scores.
- Histological analysis evaluated myocardial damage, interstitial fibrosis, vasculopathy, and transforming growth factor-beta (TGF-β) expression after 60 days.
Main Results:
- The new HTK-based solution resulted in significantly shorter re-beating times and higher palpation scores compared to traditional HTK.
- Hearts preserved with the new solution exhibited lower myocardial injury scores, reduced interstitial fibrosis (p<0.05), and less vasculopathy.
- A significant reduction in TGF-β1 expression was observed in the new solution group compared to the traditional HTK group.
Conclusions:
- The novel HTK-based preservation solution effectively reduces chronic isograft injury in heart transplantation.
- The protective effects are attributed to modifications including N-acetyl-L-histidine, glycine, alanine, arginine, and sucrose.
- This improved solution holds promise for enhancing long-term heart transplant graft survival and function.
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%).
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.
