The morbidity and mortality of patients undergoing lung transplantation in the acute phase
following surgical intervention is mainly due to the primary graft failure (PGF).
The occurrence of PGF is multi factorial but is mainly caused by ischemia-reperfusion injury.
The pulmonary graft suffers two periods of ischemia one when it is explanted from the donor
(cold ischemia) followed by another when it is grafted into the recipient's thoracic cavity
(warm ischemia). The brutal reperfusion of the graft exposes it to reperfusion injury that
causes PGF. PGF occurs in up to 20% of transplanted patients and is associated with
significantly higher levels of 30-days all-cause mortality. Patients with PGF have a 40%
mortality at 30-days versus a 6% mortality in patients without PGF.
Ischemic postconditioning, has recently been described in experimental models of
ischemia-reperfusion injury in the heart, and although not yet fully understood. Several
studies suggest that the mitochondria play a central role in cellular survival mechanisms
after a prolonged period of ischemia-reperfusion (with the mitochondrial permeability
transition pore (mPTP)).
Experimental studies have shown that cyclosporin A (CsA) administered prior to reperfusion
binds to cyclophilin D and blocks the opening of mPTP after reperfusion. This protective
effect of ischemia-reperfusion injury by CsA has been shown in experimental studies and in
clinical phase II trials in reperfused myocardial infarction patients.
The hypothesis of this study is that the administration of CsA in transplanted patients
(before re-opening of the first pulmonary graft vessels) protects the transplanted lung(s)
from the deleterious effects of ischemia-reperfusion injury and thus reduce the frequency and
severity of PGF.