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Impact of PAF antagonist BN 52021 (Ginkolide B) on post-ischemic graft function in clinical lung transplantation
1Department of Cardiothoracic and Vascular Surgery, Friedrich-Schiller University, Jena, Germany. Th.Wittwer-MD@t-online.de
Background:
Platelet activating factor (PAF) is associated with ischemia/reperfusion injury (I/R) after lung transplantation. Following promising experimental results, this prospective trial investigated the potential effect of PAF antagonist BN 52021 (ginkolide B) on clinical Euro-Collins (EC)-based lung preservation.
Methods:
We analyzed 8 double-lung transplant patients in each of 3 groups. In the low-dose group (LDG), donor lungs were perfused with EC containing 2 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 administered intravenously 120 mg BN 52021 (LDG), 600 mg BN 52021 (HDG), or placebo (CG). Hemodynamics in terms of pulmonary arterial pressure, pulmonary vascular resistance and serial determinations of the alveolo-arterial oxygen difference (AaDO(2)) were recorded. We measured blood levels of PAF pre-operatively 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 HDG, with significant deterioration 10 minutes after reperfusion. In contrast, placebo led to higher PAF levels. We measured significantly lower PAF concentrations (HDG vs CG) at 10 minutes and at 6 days post-operatively.
Conclusions:
Use of high-dose PAF antagonist BN 52021 can easily be combined with clinical preservation methods and may help optimize pulmonary function with reduced PAF levels, in the early post-ischemic period.
Insights
High-dose ginkgolide B (BN 52021) improved lung function after transplantation by reducing platelet-activating factor (PAF). This PAF antagonist shows promise for optimizing early post-ischemic lung preservation.
Area of Science:
- Transplantation immunology
- Pharmacology
- Cardiopulmonary medicine
Background:
- Platelet-activating factor (PAF) is implicated in ischemia/reperfusion (I/R) injury following lung transplantation.
- Experimental studies suggested PAF antagonists may mitigate I/R injury.
- This trial evaluated BN 52021 (ginkgolide B) in clinical lung preservation.
Purpose of the Study:
- To investigate the efficacy of PAF antagonist BN 52021 in clinical lung preservation.
- To assess the impact of BN 52021 on ischemia/reperfusion injury markers.
- To evaluate the effect on early post-transplant pulmonary function.
Main Methods:
- Prospective trial involving 24 double-lung transplant patients across three groups: low-dose BN 52021 (LDG), high-dose BN 52021 (HDG), and placebo (CG).
- Donor lungs preserved with Euro-Collins (EC) solution containing BN 52021 (2 mg/kg LDG, 10 mg/kg HDG) or placebo.
- Intravenous administration of BN 52021 or placebo prior to reperfusion.
- Monitoring of hemodynamic parameters (pulmonary arterial pressure, vascular resistance) and alveolo-arterial oxygen difference (AaDO2).
- Serial measurement of blood PAF levels pre- and post-operatively.
Main Results:
- A trend towards improved AaDO2 observed in LDG and HDG compared to CG within 32 hours.
- Significant AaDO2 improvement at 3 hours (HDG) and 8 hours (LDG) post-reperfusion.
- Lowest PAF concentrations in HDG, with significant reduction at 10 minutes and 6 days post-operatively compared to CG.
- Placebo group exhibited higher PAF levels post-reperfusion.
Conclusions:
- High-dose PAF antagonist BN 52021 is compatible with clinical lung preservation methods.
- BN 52021 effectively reduces PAF levels in the early post-ischemic period.
- This intervention may optimize early pulmonary function after lung transplantation.
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