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

Cells. 2022 May 16;11(10):1653. doi: 10.3390/cells11101653.

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.

Keywords: animal research; heart transplant; murine model; organ preservation; preservation solutions; static cold storage.

MeSH terms

  • Animals
  • Dextrans
  • Disaccharides
  • Gluconates / pharmacology
  • Glutathione
  • Heart Transplantation* / methods
  • Humans
  • Ischemia
  • Mice
  • Organ Preservation / methods
  • Organ Preservation Solutions* / pharmacology
  • Perfusion / methods
  • Tissue Donors

Substances

  • Dextrans
  • Disaccharides
  • Gluconates
  • Organ Preservation Solutions
  • lactobionic acid
  • Glutathione

Grants and funding

This research received no external funding.