OBJECTIVES: Long-time preservation of the donor heart before transplantation is 
associated with mitochondrial damages resulting in functional deterioration 
after transplantation, although the exact mechanism behind this is still 
uncertain. Here, we have demonstrated the opening of a nonspecific pore in the 
inner membrane of the mitochondria, the mitochondrial permeability transition 
pore (PTP), as one of the reasons responsible for this functional deterioration.
METHODS: After 30 minutes of perfusion with the Krebs Henseleit buffer at 37 
degrees C in working mode, hearts from Wistar rats were arrested with ice-cold 
St. Thomas cardioplegic solution and preserved University of Wisconsin solution 
at 4 degrees C with or without inhibiting the PTP with cyclosporin A (CsA) (0.2 
microM). After 12 hours, the hearts were reperfused for 60 minutes at 37 degrees 
C with or without perfusing the hearts during first 15 minutes of reperfusion 
with PTP openers lonidamine (30 microM) or atractyloside (20 microM).
RESULTS: Inhibiting PTP with CsA resulted in (a) significant recovery of cardiac 
functions, (b) well-preserved myocardial adenosine triphosphate (ATP) levels 
(P<0.001), (c) less myocardial water content (P<0.01), (d) less mitochondrial 
swelling and cytochrome C release, and (e) up-regulation of Bcl-2 expression 
compared with the control hearts without PTP inhibition. These effects are 
completely inhibited on opening the PTP before preservation, resulting in poor 
recovery of cardiac functions, loss of myocardial ATP, and severe mitochondrial 
swelling.
CONCLUSION: The present study demonstrates the potential role of mitochondrial 
PTP after long- time hypothermic preservation of the heart, and therefore, 
regulation of PTP would prolong the preservation time of donor hearts.