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/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.
Department of Cardiothoracic and Vascular Surgery, Friedrich-Schiller University, Jena, Germany. Th.Wittwer-MD@t-online.de
T
T
Wittwer
M
M
Grote
P
P
Oppelt
U
U
Franke
H J
HJ
Schaefers
T
T
Wahlers
D004224:Diterpenes; D004311:Double-Blind Method; D046934:Ginkgolides; D006439:Hemodynamics; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008171:Lung Diseases / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects; D010100:Oxygen / Q000097:blood; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B; D010100:Oxygen