Gluconate-Lactobionate-Dextran Perfusion Solutions Attenuate Ischemic Injury and Improve Function in a Murine Cardiac Transplant Model

Abstract

Static cold storage is the cheapest and easiest method and current gold standard to store and preserve donor organs. This study aimed to compare the preservative capacity of gluconate-lactobionate-dextran (Unisol) solutions to histidine-tryptophan-ketoglutarate (HTK) solution. Murine syngeneic heterotopic heart transplantations (Balb/c-Balb/c) were carried out after 18 h of static cold storage. Cardiac grafts were either flushed and stored with Unisol-based solutions with high-(UHK) and low-potassium (ULK) ± glutathione, or HTK. Cardiac grafts were assessed for rebeating and functionality, histomorphologic alterations, and cytokine expression. Unisol-based solutions demonstrated a faster rebeating time (UHK 56 s, UHK + Glut 44 s, ULK 45 s, ULK + Glut 47 s) compared to HTK (119.5 s) along with a better contractility early after reperfusion and at the endpoint on POD 3. Ischemic injury led to a significantly increased leukocyte recruitment, with similar degrees of tissue damage and inflammatory infiltrate in all groups, yet the number of apoptotic cells tended to be lower in ULK compared to HTK. In UHK- and ULK-treated animals, a trend toward decreased expression of proinflammatory markers was seen when compared to HTK. Unisol-based solutions showed an improved preservative capacity compared with the gold standard HTK early after cardiac transplantation. Supplemented glutathione did not further improve tissue-protective properties.

Successful Extension of Vascularized Composite Allograft Perfusion Cold Storage to 24 h in a Rat Hindlimb Transplant Model

“…It is likely that the most significant factor contributing to excessive cell death in ex vivo machine perfusion is the perfusion solution itself. 32,33,35 Although not a clinical standard, NS has previously been used in practice for the flushing of grafts; however, our results show that it causes extensive damage to skeletal muscle when used for VCA HMP storage. In contrast, KPS-1 demonstrated the ability to significantly reduce TUNEL staining, CC3 staining, and histological markers of apoptosis and necrosis compared with NS.…”

Freezing Biological Time: A Modern Perspective on Organ Preservation

“…Post-thaw survival results were equivalent or improved, as compared to traditional water bath approaches, depending on the freezing media used 18 . Solutions designed to mimic the intracellular milieu that restrict passive ion fluxes across cell membranes, rather than plasma-like extracellular formulations such as culture media, are often best for hypothermic cell storage as well as cryopreservation 19 . Adherent cells may be particularly difficult to rewarm with retention of good viability.…”