Impact of PAF antagonist BN 52021 (Ginkolide B) on post-ischemic graft function in clinical lung transplantation

Background: Platelet activating factor (PAF) is associated with ischemia/re perfusion injury (I/R) after lung transplantation. Following promising expe rimental results, this prospective trial investigated the potential effect of PAF antagonist BN 52021 (ginkolide B) on clinical Euro-Collins (EC)-base d lung preservation. Methods: We analyzed 8 double-lung transplant patients in each of 3 groups. Tn the low-dose group (LDG), donor lungs were perfused with EC containing 3 mg/kg BN 52021, whereas we used 10 mg/kg in the high-dose group (HDG) and placebo in the control group (CG). Before reperfusing the first lung, we a dministered intravenously 120 mg BN 52021 (LDG), 600 mg BN 52021 (HDG), or placebo (CG). Hemodynamics in terms of pulmonary arterial pressure, pulmona ry vascular resistance and serial determinations of the alveolo-arterial ox ygen difference (AaDO(2)) were recorded. We measured blood levels of PAF pr eoperatively and post-operatively, after 10 minutes and after 3, 8, 24, 48, and 144 hours. Results: Within 32 hours, we noted a tendency toward better AaDO(2) in the LDG and the HDG compared with the CG (p > 0.05). We observed a significant improvement of AaDO(2) after 3 hours (HDG, p = 0.033) and 8 hours (LDG, p = 0.024), with poorest values in the CG. The PAF concentrations were lowest in the HDC, with significant deterioration 10 minutes after reperfusion. In contrast, placebo led to higher PAF levels. We measured significantly lowe r PAF concentrations (HDC vs CG) at 10 minutes and at 6 days post-operative ly. Conclusions: Use of high-dose PAF antagonist BN 52021 can easily be combine d with clinical preservation methods and may help optimize pulmonary functi on with reduced PAF levels, in the early post-ischemic period.