University of Wisconsin solution

University of Wisconsin solution. It is a specialized Hypothermic Organ preservation fluid developed to extend the viable storage time of donor organs prior to Organ transplantation. First introduced clinically in 1987, it represented a major advancement over previous solutions like Euro-Collins solution and allowed for the reliable preservation of abdominal organs such as the Liver, Pancreas, and Kidney. Its formulation is designed to minimize Cellular edema, prevent Intracellular acidosis, and counteract injury from Reactive oxygen species during the Ischemia of Static cold storage.

History and development

The solution was developed in the late 1980s at the University of Wisconsin–Madison by a team led by surgeon Folkert O. Belzer and biochemist James H. Southard. Their research was driven by the clinical need to safely preserve organs for longer periods, facilitating better Organ matching and long-distance Organ procurement. A key breakthrough was the successful multi-day preservation of the Canine Pancreas, which demonstrated unprecedented efficacy. Following pivotal trials, it received approval from the Food and Drug Administration and was commercially marketed as Viaspan by Bristol-Myers Squibb. Its adoption revolutionized the logistics of Liver transplantation and Pancreas transplantation worldwide.

Composition and formulation

The solution is a complex, intracellular-type fluid with multiple specific components. Key impermeants include Lactobionate and Raffinose, which are large molecules that counteract Osmotic pressure and prevent cellular swelling. Hydroxyethyl starch serves as a Colloid to suppress interstitial edema. Important additives for Cellular metabolism and protection include Adenosine (a precursor for Adenosine triphosphate synthesis), Allopurinol (a Xanthine oxidase inhibitor), Glutathione (an Antioxidant), and Insulin. Magnesium sulfate and Potassium phosphate are included as Electrolyte buffers, while Penicillin G and Dexamethasone are common antibiotic and anti-inflammatory adjuncts.

Mechanism of action

Its primary mechanism during Hypothermic Static cold storage is to maintain Cellular homeostasis and minimize Reperfusion injury. The impermeants Lactobionate and Raffinose create an osmotic gradient that counteracts the influx of water into cells, thereby preventing lethal Cellular edema. Adenosine helps replenish Adenosine triphosphate stores upon Reperfusion. Glutathione and Allopurinol work to scavenge Reactive oxygen species generated during ischemia and subsequent Oxidative stress. The solution also helps stabilize Cell membranes and inhibits the activation of damaging Proteases and Phospholipases that occur during cold ischemia.

Clinical applications

It became the gold-standard solution for the Static cold storage of abdominal organs, profoundly impacting Transplant surgery. Its most significant application is in Liver transplantation, where it reliably permits preservation times of up to 12-15 hours, compared to much shorter times with prior solutions. It is also standard for the preservation of the Pancreas for Pancreas transplantation and is frequently used for the Kidney, though some centers prefer other solutions like Histidine-tryptophan-ketoglutarate solution for renal grafts. Its use is integral to the protocols of Organ procurement organizations like the United Network for Organ Sharing.

Comparison to other preservation solutions

Compared to the earlier extracellular-type Euro-Collins solution, it provides superior protection against Cellular edema and Oxidative stress, leading to significantly longer safe preservation times for the Liver. The Histidine-tryptophan-ketoglutarate solution, developed later in Europe, is also an intracellular-type solution but has a lower viscosity and different buffer system, making it popular for Kidney and some Liver transplants. Solutions like Celsior and Custodiol are often used in Cardiac surgery and Thoracic transplantation, whereas the University of Wisconsin solution remains dominant for abdominal organs.

Modifications and variants

Several modified versions have been developed to simplify the formula or target specific injuries. One common variant omits the expensive and potentially allergenic Hydroxyethyl starch, creating a lower-viscosity solution. Other research formulations have experimented with different Antioxidant additives, such as N-acetylcysteine or Trimetazidine. For machine perfusion techniques like Hypothermic machine perfusion, the basic electrolyte and impermeant composition is often used but may be adjusted. These variants are studied in institutions like the Mayo Clinic and Cleveland Clinic to further optimize outcomes in Transplant medicine. Category:Organ transplantation Category:Medical treatments