Abstract
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 (AaDO2) 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 AaDO2 in the LDG and the HDG compared with the CG (p > 0.05). We observed a significant improvement of AaDO2 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.
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References
- Experience with lung transplantation.Ann Thorac Surg. 1999; 76: 305-312
- Platelet activating factor (PAF). A review of its effects, antagonists and possible future clinical implications (Part I).Drugs. 1991; 42: 9-29
- Hypoxia-induced interleukin-6 and interleukin-8 production is mediated by platelet-activating factor and platelet-derived growth factor in primary human lung cells.Am J Respir Cell Mol Biol. 1998; 19: 653-661
- Studies on the mechanism of PAF-induced vasopermeability in rat lungs.Prostaglandins Leukot Essent Fatty Acids. 1995; 52: 245-249
- Platelet-activating factor plays a pivotal role in the induction of experimental lung injury.Am J Respir Cell Mol Biol. 1998; 18: 197-204
Coyle AJ, Page EP. The role of PAF in pulmonary pathology. In: Handley DA, Saunders RN, Houlihan WJ, Tomeseh DC, eds. Platelet activating factor in endotoxin and immune disease. New York: Marcel Dekker, 1990, pp. 285–307.
- Future horizons of lung preservation by application of a platelet-activating factor antagonist compared with current clinical standards. Euro-Collins flush perfusion versus donor core cooling.J Thorac Cardiovasc Surg. 1992; 103: 200-204
- Donor administration of PAF antagonist (TCV-309) enhances lung preservation.Transplant Proc. 1995; 27: 570-573
- Extended lung preservation with platelet-activating factor-antagonist TCV-309 in combination with prostaglandin E1.J Heart Lung Transplant. 1997; 16: 946-955
- A new platelet-activating factor antagonist (CV-6209) in preservation of heart and lung for transplantation.Cardiovasc Drugs Ther. 1997; 11: 777-785
- The role of platelet-activating factor (PAF) in interstitial pulmonary disease.J Invest Allergol Clin Immunol. 1994; 4: 149-157
Patterson GA, Cooper JD. Lung transplantation. In: Pearson FG, Deslauriers J, Ginsberg RJ, Hiebert C, McKneally MF, Urschel HC, ed. Thoracic surgery. New York: Churchill Livingstone, 1995, pp. 931–59.
- Regulation of eicosanoid generation in activated macrophages.Int Arch Allergy Appl Immunol. 1991; 95: 77-85
Anderson G, Fennessy M. Eicosanoids and the bronchopulmonary effects of platelet-activating factor. In: Handley DA, Saunders RN, Houlihan WJ, Tomesch JC, eds. Platelet-activating factor in endotoxin and immune diseases. New York: Marcel Dekker, 1990, pp. 329–50.
Qayumi AK, Jamieson WRE. Pathophysiology of reperfusion injury in organ transplantation. In: Das DK, ed. Pathophysiology of reperfusion injury. Boca Raton: CRC Press, 1993, pp. 325–62.
- Long-term lung preservation with the PAF antagonist BN52021.Transplantation. 1991; 51: 1152-1156
- Platelet activating factor antagonist enhances lung preservation.J Surg Res. 1992; 52: 615-620
- Anti-inflammatory properties of a platelet-activating factor acetylhydrolase.Nature. 1995; 374: 549-552
- Protection against oxidative stress-induced cell death by intracellular platelet-activating factor-acetylhydrolase II.J Biol Chem. 1997; 272: 32315-32320
Article info
Publication history
Accepted:
October 12,
2000
Received:
June 2,
2000
Identification
Copyright
© 2001 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
