Effect of cyclosporine A in ex vivo reperfused pig lungs

Rationale: The ex vivo pulmonary reperfusion is a suitable method of evaluation of lung ischemia reperfusion injuries (IRI). The role of the Cyclosporine A (CsA) in the prevention of IRI has been shown in different organs of several animal species but not clearly evaluated in lungs. Our objective was to evaluate the effects of CsA in ex vivo reperfused pig lungs. Methods: 10 lungs were perfused with an extracorporeal perfusion circuit, and mechanically ventilated. CsA was administered before and during reperfusion procedure (either at 1 or 30μM). Results: Lungs treated by 30 μM of CsA had increased capillary pressure (Pcap), pulmonary vascular resistances (PVR), lung permeability to proteins, IL1 beta and TNF alpha concentrations in bronchoalveolar lavage (BAL). 1μM of CsA seemed to have no effect compared to control group. Lungs parameters Pcap PVR total K [IL1β] in BAL [TNFα] in BAL (mmHg) (mmHg/l/min) (min –1 ) (pg/mL) (pg/mL) Control (n=4) 7.62±1.20 9.54±0.62 0.006±0.004 66.1±70.1 17.7±25.8 CsA 1μM (n=3) 8.80±1.19 13.08±4.99 0.012±0.010 78.3±92.7 10.0±14.1 CsA 30μM (n=3) 13.37±3.39* 16.02±1.53* 0.024±0.009* 198.2±2.1* 46.3±10.7* *p<0.05 between control and CsA 30μM ; K = coefficient of permeability to Dextran of the capillary-alveolar membrane. Discussion: CsA, at the concentration of 30 μM, seems to be deleterious in lung IRI. The hemodynamic effects of CsA may explain these results.