Prolonged Mouse Cardiac Graft Cold Storage via Attenuating Ischemia-Reperfusion Injury Using a New Antioxidant-Based Preservation Solution

Transplantation. 2016 May;100(5):1032-40. doi: 10.1097/TP.0000000000001079.

Abstract

Background: One of the major events in ischemia-reperfusion (I/R)-induced heart injury in cardiac transplantation is the generation of reactive oxygen species. We hypothesized that a novel preservation solution called SBI-SEIIKU II (SS-II) contains 3 antioxidant reagents: L-cysteine, glycine, ascorbic acid/ascorbic acid-2-phosphate magnesium, which can block the generation of reactive oxygen species to result in a prolongation of the cold storage time via attenuating I/R injury.

Methods: C57BL/6CrSlc(B6) mice underwent syngeneic mice heterotopic heart transplantation, and the animals were derived into 3 groups: recipients with nonpreserved grafts (control group), recipients with grafts preserved in histidine-tryptophan-ketoglutarate (HTK) for 24 and 48 hours (HTK group), and recipients with grafts preserved in SS-II for 24 and 48 hours (SS-II group).

Results: After 48 hours of preservation, there were no grafts that survived in the HTK group; however, the SS-II group had a high survival rate. After 24 hours of preservation, SS-II decreased the oxidative damage, myocardial apoptosis, and the infiltration of macrophages and neutrophils in the cardiac grafts in the early phase and suppressed the development of myocardial fibrosis in long-term grafts compared with HTK.

Conclusions: The SS-II prolongs the acceptable cold storage time and protects the myocardium from I/R injury via inhibiting oxidative stress-associated damage. We believe that this novel preservation solution may be simple and safe for use in the clinical transplantation field.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry*
  • Apoptosis
  • Ascorbic Acid / analogs & derivatives
  • Ascorbic Acid / chemistry
  • Cold Temperature*
  • Cryopreservation
  • Cysteine / chemistry
  • Glycine / chemistry
  • Graft Survival
  • Heart / drug effects
  • Heart Injuries / pathology
  • Heart Transplantation / methods*
  • Heme Oxygenase-1 / metabolism
  • Macrophages / metabolism
  • Magnesium / chemistry
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • Myocardium / metabolism
  • Neutrophils / metabolism
  • Organ Preservation
  • Organ Preservation Solutions / chemistry*
  • Organophosphorus Compounds / chemistry
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / therapy*
  • Time Factors

Substances

  • Antioxidants
  • Membrane Proteins
  • Organ Preservation Solutions
  • Organophosphorus Compounds
  • Reactive Oxygen Species
  • ascorbate-2-polyphosphate
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Magnesium
  • Cysteine
  • Ascorbic Acid
  • Glycine