Role of temperature in reconditioning and evaluation of cold preserved kidney and liver grafts

Abstract

Purpose of review: Organ shortage in transplantation medicine forces surgical research toward the development of more efficient approaches in organ preservation to enable the application of 'less than optimal' grafts. This review summarizes current techniques aiming to recondition cold-stored organ grafts prior to transplantation to reduce reperfusion-induced tissue injury and improve postimplantation graft function.

Recent findings: End-ischemic reconditioning has classically been attempted by cold oxygenated perfusion. By contrast, evaluation of graft performance prior to transplantation might be facilitated by perfusion at higher temperatures, ideally at normothermia. A drastic temperature shift from cold preservation to warm perfusion, however, has been incriminated to trigger a so-called rewarming injury associated with mitochondrial alterations. A controlled gradual warming up during machine perfusion could enhance the restitution of cellular homeostasis and improve functional outcome upon warm reperfusion.

Summary: Machine perfusion after conventional cold storage is beneficial for ulterior function after transplantation. Cold grafts should be initially perfused at low temperatures allowing for restitution of cellular homeostasis under protective hypothermic limitation of metabolic turnover. Delayed slow rewarming of the organ might further mitigate rewarming injury upon reperfusion and also increases the predictive power of evaluative measures, taken during pretransplant perfusion.

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FIGURE 1

Impact of reperfusion temperature on enzyme release after cold preservation. Rat livers retrieved 30 min after cardiac standstill and cold stored for 18 h in HTK solution. Reperfusion was performed with fully oxygenated Williams-E solution at the indicated temperatures, and cumulative release of mitochondrial glutamate dehydrogenase was recorded during 2 h. Values are mean ± SD from n = 5 per group; ^{∗, ∗∗}P < 0.05 vs. 4 and 22 °C, respectively, by Tukey–Kramer multiple comparisons test. HTK, histidine-tryptophan-ketoglutarate solution.

FIGURE 2

Schematic illustration of mitochondrial rewarming injury.