Post-conditioning with Cyclosporine A after a 24-hour cold ischemia in ex vivo reperfused pig lungs

ABSTRACT

Objective: To evaluate the effects of 1 and 5 μM of Cyclosporine A (CsA), administered 24 hours after a cold ischemic period, in an ex vivo reperfused pig lung model. Methods: The experiments were performed in 15 pigs. Each pair of lungs was surgically separated. Extracorporeal perfusion and mechanical ventilation were started after a cold ischemia of 2 hours for one lung and 24 hours for the contralateral. We constituted three groups (n = 5 each): two groups for which the lung underwent a 24-hour ischemia received either 1 or 5 μM of CsA at the time of reperfusion, and a control group without CsA. For each group, lungs undergoing a 2-hour ischemia did not receive CsA. Results: Reperfusion with either CsA increased the PO₂ levels in a dose dependent manner, and reduced concentrations of the receptor for advanced glycation endproducts, compared to the control. The pulmonary arterial pressure, the capillary pressure, and the pulmonary vascular resistances were not increased, even with 5 μM of CsA. No significant change was shown on cytokines levels. Discussion: Postconditioning with CsA improves lung function, after a 24-hour cold ischemic period. Either 1 or 5 μM seemed to be safe regarding the pulmonary vascular pressures and resistances.

KEYWORDS :

• experimental
• ischemia reperfusion injury
• pulmonary edema
• transplantation