Kfc determination after ischemia-reperfusion in lungs treated with sildenafil and tadalafil

Ischemia reperfusion phenomenon (IR) is the major factor implicated in primary graft failure, condition that occurs around the 20% of the lung transplants. Some drugs in theory can diminish the IR injury. Sildenafil and tadalafil are drugs that inhibit the 5-Phosphodiesterase, enzyme that inhibits cGMP, leading to vasoconstriction, edema and finally organ failure. The inhibition of 5-phosphodiesterase results in dilatation of pulmonary vasculature and lower hydrostatic pressure, likely decreasing edema formation. The objective of this study was to determinate the edema formation in lungs treated with Sildenafil and tadalafil in animal (ex vivo) model of ischemia-reperfusion. Lung blocks were harvested (Wistar rats) and distributed in the following groups (G): G I: immediately reperfusion. G II: 8 hours preservation, and reperfusion. G III and G IV: Sildenafil (0.7 mg/kg) or tadalafil (0.15 mg/kg) donor pretreatment respectively, 8 hours preservation, and reperfusion. Pulmonary arterial pressure (PAP), pulmonary venous pressure (PVP), lung difference weight (W), pulmonary capillary pressure (PCP) and the capillary filtration coefficient (Kfc) were measured. Results: (mean ± SE). PAP (mmHg): G I: 20.31±1.23, G II: 25.53 ±3.31, G III: 20.78±0.90, G IV: 18.94±1.87. Kfc (ml/min/cmH2O/100gr): G I: 0.18±0.047 G II: 0.99±0.89 G III: 0.34±0.12 G IV: 1.81±0.90*. p=<0.05. Conclusion: Donor pretreatment with sildenafil decrease PAP and edema formation compared with lungs without pretreatment (not statistical significant). The use of tadalafil decrease the PAP (not statistical significant) but increase the lung edema formation (statistical significant) compared with control lungs.