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Updated: Jun 17, 2025
Rat Model of Normothermic Ex-Situ Perfused Heterotopic Heart Transplantation
Published on: April 21, 2023
Mitochondrial Function After Normothermic Regional Perfusion or Direct Procurement Followed by Hypothermic Oxygenated
Katrine Berg1,2, Imran Ertugrul3, Jacob M Seefeldt1,2
1Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Background:
Strategies to minimize ischemic damage during heart transplantation (HTX) by donation after circulatory death (DCD) are warranted because the inevitable ischemic injury linked to DCD HTX deteriorates mitochondrial respiratory capacity and ultimately graft quality. This study aimed to examine the myocardial mitochondrial function during DCD HTX with hypothermic oxygenated machine perfusion (HOPE) and compare the effect of normothermic regional perfusion (NRP) with that of direct procurement and perfusion (DPP).
Methods:
A porcine DCD HTX model was used with hearts subjected to either DPP (n = 6) or NRP (n = 7) followed by HOPE and orthotopic HTX. Mitochondrial respiratory function was analyzed by high-resolution respirometry in left ventricle biopsies at baseline, after 180 min of HOPE, and after 60 min of reperfusion post-HTX.
Results:
Mitochondrial oxidative phosphorylation ( P = 0.0008), respiratory control ratio ( P = 0.04), and coupling efficiency ( P = 0.04) declined during DCD HTX. Fatty acid oxidation was preserved after 3 h of HOPE with a modest, statistically nonsignificant decline after reperfusion ( P = 0.2). Oxidative phosphorylation was inversely correlated with troponin-T levels ( r = -0.70, P = 0.0004). No statistically significant difference in mitochondrial respiratory capacity was observed between participants exposed to NRP and DPP.
Conclusions:
Mitochondrial respiratory capacity declined gradually throughout the course of DCD HTX and correlated with the degree of myocardial damage. Following HOPE, the extent of mitochondrial deterioration was comparable between NRP and DPP.
