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Updated: Feb 7, 2026

Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats
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Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats

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Reducing mitochondrial dysfunction through combination therapy to limit ischemia-reperfusion injury in male DCD rats

Zachary Kiernan1, Gina Labate1, Qun Chen2,3

  • 1Division of Cardiothoracic Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA, United States.

Frontiers in Cardiovascular Medicine
|February 6, 2026
PubMed
Abstract

Insights

Cyclosporine A (CyA) effectively reduced infarct size in donation after circulatory death (DCD) rat hearts with extended warm ischemia. Combination therapy with MDL-28170 (MDL) showed no synergistic benefit, indicating mitochondrial permeability transition pore opening is a key factor in DCD heart IRI.

Area of Science:

  • Cardiology
  • Transplantation Biology
  • Ischemia Reperfusion Injury Research

Background:

  • Donation after circulatory death (DCD) hearts face ischemia reperfusion injury (IRI).
  • Mitochondrial permeability transition pore (MPTP) opening and Calpain-1 (CPN1) activation are key IRI pathways.
  • Inhibitors Cyclosporine A (CyA) and MDL-28170 (MDL) modulate IRI in DCD hearts with shorter warm ischemia times (WIT).

Purpose of the Study:

  • To investigate the effect of co-administering CyA and MDL during reperfusion on infarct size and graft function in DCD rat hearts with extended WIT (35 min).

Main Methods:

  • Male rats underwent 35 min warm ischemia followed by 90 min reperfusion.
  • Hearts received CyA, MDL, or a combination of both during reperfusion.
  • Cardiac function, coronary flow, and infarct size were assessed.

Main Results:

  • CyA treatment resulted in a significant reduction in infarct size (25.49%) compared to MDL (33.26%).
  • Combined CyA + MDL treatment (31.59%) did not show synergistic benefits over CyA alone.
  • Graft function and coronary flow rates were variable across groups.

Conclusions:

  • MPTP opening is a significant contributor to IRI in DCD hearts.
  • CyA is more effective than MDL in reducing infarct size in this model.
  • Combined therapy offers no additional advantage over CyA monotherapy.
Keywords:
MDL-28170MPTPcyclosporine Adonation after circulatory deathheart failure

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