Cardioplegic Machine Perfusion of Hearts Donated after Circulatory Death

Lars Saemann1,2, Kristin Wächter3, Anne Großkopf3

  • 1Department of Cardiac Surgery, University Hospital Halle (Saale), University of Halle, Ernst-Grube-Straße 40, 06120, Halle (Saale), Germany. Lars.saemann@uk-halle.de.

Insights

Ex-vivo machine perfusion (EVMP) with HTK-N solution improved heart function and microcirculation in donor hearts after circulatory death (DCD) compared to Del Nido cardioplegia (DNC). This approach also positively regulated longevity and aging pathways.

Area of Science:

  • Cardiology
  • Transplantation Immunology
  • Organ Preservation

Background:

  • Donor hearts after circulatory death (DCD) present preservation challenges.
  • Standard cardioplegia solutions may limit the viability of DCD hearts.
  • Ex-vivo machine perfusion (EVMP) offers a dynamic approach to organ preservation.

Purpose of the Study:

  • To compare the efficacy of EVMP using HTK-N versus Del Nido cardioplegia (DNC) for preserving DCD hearts.
  • To evaluate the impact on left-ventricular (LV) contractility and myocardial microcirculation.
  • To analyze transcriptomic differences associated with each preservation method.

Main Methods:

  • Utilized a DCD pig model for heart transplantation.
  • Hearts underwent EVMP with either HTK-N or DNC under hypothermic, oxygenated conditions.
  • Assessed LV contractility (ESP, dp/dtmax, dp/dtmin) and microcirculation (Laser-Doppler-Flow) post-reperfusion.
  • Performed transcriptomic analysis using microarrays.

Main Results:

  • DCD hearts preserved with HTK-N via EVMP demonstrated significantly higher LV contractility (ESP, dp/dtmax, dp/dtmin) compared to DNC.
  • Relative myocardial microcirculation (Laser-Doppler-Flow) was superior in the HTK-N group.
  • Transcriptomic analysis revealed differential regulation of inflammatory, signaling, and cell death pathways.
  • Longevity-associated pathways were upregulated, while aging-associated pathways were downregulated in the HTK-N group.

Conclusions:

  • EVMP of DCD hearts with HTK-N leads to superior left-ventricular function and myocardial microcirculation compared to DNC.
  • HTK-N preservation influences key molecular pathways relevant to short- and long-term organ health.
  • This study highlights the potential of EVMP with HTK-N for improving outcomes in DCD heart transplantation.