Histidine-tryptophan-ketoglutarate and delayed graft function after prolonged cold ischemia.

Area of Science:

• Transplantation immunology
• Organ preservation solutions
• Biochemistry of ischemia

Background:

• Histidine-tryptophan-ketoglutarate (HTK) solution is compared to University of Wisconsin (UW) solution for organ preservation.
• HTK shows comparable or superior results to UW for short cold ischemia times.
• HTK is less efficient for extended cold ischemia, leading to increased delayed graft function.

Purpose of the Study:

• To investigate the reasons behind HTK's inefficiency for prolonged cold ischemia.
• To evaluate energy levels, metabolites, and histological changes in HTK-preserved organs.
• To understand the biochemical basis of delayed graft function associated with HTK.

Main Methods:

• Rat livers were perfused with either HTK or UW preservation solutions.
• Tissue samples were collected at various time points.
• Analysis included adenine triphosphate and metabolite levels via high-performance liquid chromatography and histological examination.

Main Results:

• HTK-perfused livers showed a plateau in high energy charge for 5 minutes, followed by a decrease after 60 minutes.
• Excess glucose initially caused the plateau, but it was consumed after 1 hour.
• HTK-preserved livers had low uridine levels, essential for glycogen synthesis, unlike UW-preserved livers.

Conclusions:

• HTK is effective for up to 2 hours of cold ischemia, after which its benefits diminish.
• Longer HTK perfusion results in low energy charge and absent glycogen stores, mimicking a starved state.
• UW solution maintains higher uridine levels and glycogen content, explaining better outcomes in extended preservation.