*4.2.3. Additive(s) to perfusate*

There are multiple preservation fluids currently in existence. These can be broadly classified as those that are intracellular and extracellular/intermediate in nature, based largely upon the solution's potassium content, or low viscosity compared to high viscosity solutions [70]. Common components include colloid and/or impermeants to counteract cellular edema, antioxidants for protection against ROS generation, ATP precursors to allow replenishment upon

University of Wisconsin (UW) solution remains the most popular pancreatic preservation fluid, and was initially developed specifically for this purpose [71]. It is an intracellular solution with a high potassium content and high viscosity as it contains hydroxyethyl starch, a particularly important component for pancreas preservation [24]. UW contains other components that fulfill many ideal criteria that should be exhibited by preservation fluids, including the addition of impermeants such as raffinose, the ATP precursor adenosine, and anti-oxidants such as allopurinol. [68] Histidine-tryptophan-ketoglutarate (HTK) is another commonly utilized preservation fluid for the pancreas. In contrast to UW, HTK it is an "intermediate" solution with a significantly lower potassium and sodium concentration, thereby in effect preventing ongoing organ metabolism. HTK also has low viscosity, theoretically allowing higher flow rates, and the histidine component of HTK provides it with significant buffering capacity [68, 70]. The next most commonly studied and clinically utilized pancreas perfusion and preservation fluid is Celsior, which has similar potassium content to HTK in addition to containing histidine as a buffer. It differs from HTK in that it has much higher sodium content; furthermore, it incorporates some of the advantageous constituents of UW, including similar impermeants and one shared anti-oxidant [68, 70]. Most recently, the use of Institut Georges Lopez (IGL-1) solution has been reported in pancreatic transplantation [72]. This solution has similar constituents to UW, except the sodium and potassium concentrations are reversed such that it more closely resembles the extra-cellular environment [68]. A number of other more recently developed perfusion fluids have shown good effect in the preservation of pancreata for islet cell transplantation in particular the ET-Kyoto perfusion fluid. This fluid has a high sodium:low potassium ratio, and contains trehalose to protect the cell membrane against hypothermia and the nitric oxide donor nitroglycerin that facilitates

National guidelines and/or protocols differ with respect to recommended perfusion and preservation fluids for the pancreas [45, 60, 74, 75]. UW and HTK solutions are the two most frequently recommended solutions for pancreas retrieval by such guidelines, although their utilization and volumes vary significantly. UK guidelines stipulate that *in situ* UW perfusion must be undertaken for pancreas retrieval, whilst Eurotransplant, German, and Australia/ New Zealand guidelines allow for either UW or HTK. Furthermore, none of these guidelines preclude dual perfusion when the pancreas is being retrieved, although German standards stipulate portal venous perfusion via a catheter inserted directly into the portal vein above the pancreas/duodenum [45, 60, 74, 75]. The use of Celsior or IGL-1 solution has not yet been incorporated into major National or Regional guidelines, although both have been employed

reperfusion, and buffers to retard the acidosis attendant with organ ischemia [70].

166 Organ Donation and Transplantation - Current Status and Future Challenges

vasodilatation [73].

in the clinical context [64, 65, 72, 76].

Heparin is a standard additive to the *in situ* perfusion fluid during DCD organ retrievals, including for the pancreas. Additionally, thrombolytics such as streptokinase or tissue plasminogen activator (tPA) can be added to the *in situ* perfusion fluid, or alternatively our approach is to directly inject tPA into the aorta before commencement of the cold *in situ* flush; the aim of this is to achieve a higher quality vascular flush through the clearance of microthrombi [82–84]. However no comparative evidence exists for or against the use of thrombolytics in DCD pancreas retrieval, although there is certainly enthusiasm for this approach [83, 85].
