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Time Course of High-Energy Phosphate Depletion During Cold Storage of Human Heart Grafts Using the Celsior Solution
Frank Kober1, Thierry Caus2,3, Alberto Riberi2
1Aix-Marseille Univ., CNRS UMR 7339, Centre de Résonance Magnétique Biologique et Médicale (CRMBM), Marseille, France.
Insights
High-energy phosphate compounds like phosphocreatine and adenosine triphosphate in heart grafts decrease during cold storage. Magnetic Resonance Spectroscopy can assess graft metabolic status to potentially extend preservation time.
Area of Science:
- Cardiology
- Biochemistry
- Medical Imaging
Background:
- Heart transplantation outcomes are influenced by graft quality.
- Assessing metabolic status of heart grafts during cold storage is crucial for viability.
- Current methods may not fully capture dynamic metabolic changes in preserved organs.
Purpose of the Study:
- To investigate the concentration dynamics of high-energy phosphate compounds (HEPC) in heart grafts during clinical cold storage.
- To evaluate the utility of Magnetic Resonance Spectroscopy (MRS) for non-destructive assessment of graft metabolic state.
- To correlate HEPC levels and intracellular pH with ischemic time.
Main Methods:
- Utilized Magnetic Resonance Spectroscopy (MRS) on seven discarded heart grafts.
- Monitored concentrations of Phosphocreatine (PCr), Adenosine Triphosphate (ATP), and inorganic phosphate (Pi), along with intracellular pH.
- Performed measurements at 30-minute intervals over at least 9 hours at 4°C in Celsior solution.
Main Results:
- PCr/ATP and Pi/ATP ratios decreased, and intracellular pH declined with increasing ischemic time.
- ATP concentration remained stable for up to 9 hours as long as PCr was detectable.
- Moderate acidosis was observed, and MRS provided non-destructive metabolic assessment.
Conclusions:
- MRS can assess the metabolic status of heart grafts prior to transplantation.
- HEPC metabolites deplete predictably during cold storage, indicating potential viability markers.
- Understanding HEPC dynamics and pH changes may aid in developing strategies to extend graft ischemic time.
Abstract:
The aim of this study was to provide insight into high-energy phosphate compound concentration dynamics under realistic clinical cold-storage conditions using the Celsior solution in seven heart grafts discarded from transplantation. The hearts of seven local donors (three males, four females, age 37 ± 17 years, height 175 ± 5 cm, weight 75 ± 9 kg) initially considered for transplantation and eventually discarded were submitted to a Magnetic Resonance Spectroscopy observation in a clinical Magnetic Resonance Imaging scanner over at least 9 h. The grafts remained in their sterile container at 4°C during the entire examination. Hence, Phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH were recorded non-destructively at a 30-minute interval. With the ischemic time Ti, the concentration ratios decreased at PCr/ATP = 1.68-0.0028·Tis, Pi/ATP = 1.38 + 0.0029·Tis, and intracellular pH at 7.43-0.0012·Tis. ATP concentration remained stable for at least 9 h and did not decrease as long as phosphocreatine was detectable. Acidosis remained moderate. In addition to the standard parameters assessed at the time of retrieval, Magnetic Resonance Spectroscopy can provide an assesment of the metabolic status of heart grafts before transplantation. These results show how HEPC metabolites deplete during cold storage. Although many parameters determine graft quality during cold storage, the dynamics of HEPC and intracellular pH may be helpful in the development of strategies aiming at extending the ischemic time.
