Hydroxyectoine ameliorates preservation injury in deceased after cardiac death donors in experimental liver grafts.

Abstract

BACKGROUND:

Due to the drastic shortage of organ donors, clinicians are increasingly considering the use of deceased after cardiac death donors (DCD). Compatible solutes like Ectoine and Hydroxyectoine are produced by extremophilic bacteria as a cell protectant to survive in harsh environments. We hypothesized that the addition of Hydroxyectoine to Histidine-Tryptophan-Ketoglutarate solution (HTK) could ameliorate cold ischemic preservation injury of DCD livers.

MATERIAL AND METHODS:

Rat livers were harvested from male Wistar rats weighing 250-300 g. Three experimental groups (n=5 per group) were studied: (1) CONTROLS: cold static storage in HTK for 24 h, (2) DCD: 30-min warm ischemia time and 24-h cold static storage in HTK, and (3) DCD+Hydroxyectoine: like DCD, but with 24-h cold static storage in HTK+Hydroxyectoine. Viability of the livers was assessed after 24 h of preservation by isolated perfusion for 45 min with oxygenated Krebs-Henseleit buffer solution.

RESULTS:

(mean ±SEM, Control vs. DCD vs. DCD+Hydroxyectoine) Parenchymal enzyme release was significantly lower in DCD+Hydroxyectoine compared to DCD (AST: 9±0.54; 56.8±2.05; 32.2±7.25 U/L, ALT: 9.5±0.5; 37.75±9.6; 17.5±4.17 U/L). Bile production at the end of 45 min reperfusion was significantly higher in DCD+Hydroxyectoine (5.16±1.32; 1.36±0.34; 10.75±2.24 µL/g liver weight/45 min). Malondialdehyde values were significantly lower in DCD+Hydroxyectoine (0.8±0.09, 1.14±0.18, 0.77±0.08 nmol/mL). Intercellular adhesion molecule-1 showed significantly lower values in DCD+Hydroxyectoine (219.07±51.79, 431.9±35.70, 205.2±37.71 pg/mL) and the portal venous pressure at 45 min was lower compared to DCD (20.41±0.12, 27.47±0.45, 22.08±0.78 mmHg).

CONCLUSIONS:

Our data provide evidence for the beneficial role of Hydroxyectoine-modified HTK solution for the preservation of DCD livers compared to HTK.

• Authors: Pramod Kadaba Srinivasan, Ngwi Fet, Christian Bleilevens, Mamdouh Afify, Benedict Doorschodt, Shintaro Yagi, Gerhild van Echten-Deckert, René Hany Tolba
• Journal: Annals of transplantation (Ann Transplant) Vol. 19 Pg. 165-73 (Apr 14 2014) ISSN: 2329-0358 [Electronic] United States
• PMID: 24727658 (Publication Type: Journal Article)

Chemical References

• Amino Acids, Diamino
• Krebs-Henseleit solution
• Organ Preservation Solutions
• hydroxyectoine
• Tromethamine
• Intercellular Adhesion Molecule-1
• Malondialdehyde
• Hyaluronic Acid
• Transaminases
• Glucose

Topics

• Amino Acids, Diamino (pharmacology)
• Animals
• Bile (metabolism)
• Cold Ischemia
• Cytoprotection (drug effects)
• Death
• Glucose (pharmacology)
• Graft Survival (drug effects)
• Hyaluronic Acid (metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Liver Transplantation
• Male
• Malondialdehyde (metabolism)
• Organ Preservation Solutions (pharmacology)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism, prevention & control)
• Transaminases (metabolism)
• Tromethamine (pharmacology)
• Warm Ischemia