Differential effects of ischemia/reperfusion on endothelial function and contractility in donation after circulatory

Natalia Méndez-Carmona1, Rahel K Wyss1, Maria Arnold1

  • 1Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.

Insights

Donation after circulatory death (DCD) heart ischemia impairs endothelial function earlier than cardiac function. Improving endothelial nitric oxide synthase (eNOS) coupling may enhance DCD heart recovery for transplantation.

Area of Science:

  • Cardiovascular Research
  • Transplantation Immunology
  • Organ Preservation

Background:

  • Donation after circulatory death (DCD) offers potential for increased cardiac graft availability.
  • DCD hearts face challenges from warm ischemia/reperfusion (I/R) injury.
  • Endothelial damage is a critical component of cardiac I/R injury.

Purpose of the Study:

  • Investigate the tolerance of cardiac and endothelial function to varying warm ischemia durations.
  • Inform optimal timing and selection of cardioprotective therapies for DCD hearts.
  • Determine the threshold for warm ischemia-induced endothelial dysfunction.

Main Methods:

  • Isolated, working rat hearts subjected to 20 minutes aerobic perfusion.
  • Varied durations of warm global ischemia followed by 30 or 60 minutes reperfusion.
  • Assessed cardiac function (left ventricular work) and endothelial function (vasodilation).

Main Results:

  • Cardiac function recovery reduced with ≥27 minutes ischemia.
  • Cell death and edema increased with ≥27 minutes ischemia.
  • Endothelial dysfunction observed with ≥24 minutes ischemia; eNOS uncoupling indicated by increased superoxide and peroxynitrite.

Conclusions:

  • Endothelial dysfunction occurs earlier than cardiac functional decline following ischemia.
  • Increased eNOS uncoupling may drive early endothelial dysfunction.
  • Enhancing eNOS coupling could improve DCD heart recovery and transplantation outcomes.
Abstract

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