TiProtec preserves endothelial function in a rat model

J Surg Res. 2016 Jan;200(1):346-55. doi: 10.1016/j.jss.2015.06.062. Epub 2015 Jul 2.

Abstract

Background: Coronary artery bypass surgery provides excellent patency rates; however, the early and/or late graft failure reduces the long-term benefit of myocardial revascularization. We investigated the effectiveness of generally used saline, Custodiol solutions and a new solution (TiProtec) at preserving endothelium after cold ischemia and warm reperfusion injury.

Materials and methods: Aortic transplantations were performed in Lewis rats. Aortic arches were stored in saline, Custodiol, and TiProtec solutions for 2 h then were transplanted into the abdominal aorta. Two, 24 hours and 1 week after transplantation, the implanted grafts were harvested. Endothelium-dependent and -independent vasorelaxations were investigated in organ bath. DNA strand breaks were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-method, messenger RNA expressions by quantitative real-time polymerase chain reaction, and the expression of CD-31 and alpha smooth muscle actin by immunochemistry.

Results: Severely impaired endothelial function and integrity of implanted aortic grafts were shown after 2 h in the saline, Custodiol group (maximal vasorelaxation to acetylcholine: control: 91 ± 2%, saline: 26 ± 5%, Custodiol: 24 ± 5%, CD-31-positive area control: 96 ± 2%, saline: 35 ± 13% Custodiol: 54 ± 5%, P < 0.05, respectively); however, a preserved endothelial function was observed in the TiProtec group when compared with the saline and Custodiol group (maximal vasorelaxation: 46 ± 7%, CD-31-positive area: 54 ± 10%, P < 0.05). After 1 wk, endothelial function was partially recovered in all groups; however, it was significantly better in the TiProtec group (maximal vasorelaxation to acetylcholine: saline: 42 ± 3%, Custodiol: 48 ± 3%, TiProtec: 56 ± 3%, CD-31-positive area: saline: 56 ± 5%, Custodiol: 54 ± 4%; TiProtec: 83 ± 6%, P < 0.05, respectively). In addition, messenger RNA levels of Bax, B-cell lymphoma-2, endothelial NOS, vascular endothelial growth factor 2, and caspase-3 were significantly altered in both groups.

Conclusions: TiProtec appears to be superior for the preservation of endothelial- and smooth muscle cells of bypass graft after cold storage and warm reperfusion in our murine model.

Keywords: Bypass; Endothelium; Grafting; Ischemia; Reperfusion.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Aorta, Abdominal / surgery
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiopathology
  • Aorta, Thoracic / transplantation*
  • Cold Ischemia
  • Coronary Artery Bypass
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Glucose / pharmacology
  • In Situ Nick-End Labeling
  • Male
  • Mannitol / pharmacology
  • Organ Preservation Solutions / pharmacology*
  • Potassium Chloride / pharmacology
  • Procaine / pharmacology
  • Rats
  • Rats, Inbred Lew
  • Real-Time Polymerase Chain Reaction
  • Reperfusion
  • Sodium Chloride / pharmacology
  • Vasodilation / drug effects*

Substances

  • Bretschneider cardioplegic solution
  • Organ Preservation Solutions
  • Mannitol
  • Sodium Chloride
  • Procaine
  • Potassium Chloride
  • Glucose