Platelet activating factor acetylhydrolase decreases lung reperfusion injury.
BACKGROUND
Ischemia-reperfusion injury involves free radical production, polymorphonuclear neutrophil chemotaxis/degranulation, and production of proteolytic enzymes, complement components, coagulation factors, and cytokines. Activated polymorphonuclear neutrophils, endothelial cells, and macrophages produce platelet activating factor, which further promotes these inflammatory reactions. The recently cloned plasma form of platelet activating factor-acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degrading platelet activating factor. We evaluated the effects of PAF-AH in an isolated perfused rat lung model by adding it to the flush solutions or to the reperfusion blood.


METHODS
Rat lungs were isolated, flushed with EuroCollins (EC) or University of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours, and reperfused using a cross-circulating syngeneic support rat. During reperfusion, oxygenation, compliance, and capillary filtration coefficient were calculated. There were four groups in the study; group I (control) had no PAF-AH added, group II had PAF-AH added to the flush solution, group III had PAF-AH added to reperfusion blood, and group IV had PAF-AH added to both flush solution and reperfusion blood.


RESULTS
After 6 hours of storage, oxygenation, compliance, and capillary filtration coefficient significantly improved for EC in group IV. For UW, oxygenation improved in group IV whereas compliance improved in groups II, III, and IV. After 12 hours of storage, compliance improved for EC in group IV and capillary filtration coefficient improved in groups III and IV. For UW, oxygenation and compliance improved in groups II and IV, whereas capillary filtration coefficient improved in group IV.


CONCLUSIONS
Addition of PAF-AH to intracellular organ preservation solutions and to the blood reperfusate significantly improves postreperfusion oxygenation and compliance, and reduces lung capillary permeability.
Kim
J D
JD
Department of Cardiothoracic Surgery, University of Southern California and Childrens Hospital, Los Angeles 90033, USA.
Baker
C J
CJ
Roberts
R F
RF
Darbinian
S H
SH
Marcus
K A
KA
Quardt
S M
SM
Starnes
V A
VA
Barr
M L
ML
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D005978:Glutathione; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D007328:Insulin; D008168:Lung / Q000098:blood supply*; D008297:Male; D019188:Organ Preservation Solutions; D018384:Oxidative Stress; D010741:Phospholipases A / Q000494:pharmacology*; D010972:Platelet Activating Factor; D011887:Raffinose; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*
C037096:Euro-Collins' solution; D006982:Hypertonic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; D010972:Platelet Activating Factor; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose