Hepatocyte Viability and Adenosine Triphosphate Content Decrease Linearly Over Time During Conventional Cold Storage of Rat Liver Grafts

Abstract

Introduction The gold standard in organ preservation is static cold storage (SCS) using University of Wisconsin solution (UW). While it’s known that there is a finite limit to SCS preservation, and that there is a correlation between the ATP levels and organ function post preservation, a quantitative relationship has not been established, which is important in understanding the fundamental limitations to preservation, minimizing cold ischemic injury and hence maximizing utilization of the donor organ pool. Aim To determine the time limits of cellular viability and metabolic function during SCS, and to characterize the relationship between cellular viability and energetic state, using clinically relevant techniques in organ preservation. Methods Rat livers were procured and stored using conventional storage in UW solution at 4°C. Viability was assessed by determining the amount of viable hepatocytes and intracellular ATP content after 0, 24, 48, 72 and 120 hours of storage. Results Numbers of viable hepatocytes that were isolated from these livers decreased steadily during SCS. After 5 days, viable hepatocytes decreased from 25.95×106 to 0.87×106 cells/gram tissue. Intracellular ATP content decreased from 9.63 to 0.93 μmoles/gram tissue. Statistical analysis (ANOVA) established a linear relation for both parameters as a function of time (P<0.05). Conclusion The linear correlation between hepatocyte viability, ATP content, and storage time suggests a shared physiological foundation. These findings confirm ATP as direct predictor for organ quality in the context of liver preservation, which will aid quantitative assessment of donor organs for various applications.

The Impact of Solute Carrier (SLC) Drug Uptake Transporter Loss in Human and Rat Cryopreserved Hepatocytes on Clearance Predictions

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Simple Machine Perfusion Significantly Enhances Hepatocyte Yields of Ischemic and Fresh Rat Livers

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Potential approaches to improve the outcomes of donation after cardiac death liver grafts

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