Reduced PAF-acetylhydrolase activity is associated with postinjury multiple organ failure.
Our basic laboratory work has identified the postischemic gut as a source of platelet-activating factor (PAF), which primes circulating neutrophils for the production of reactive oxygen metabolites (ROMs) leading to distant organ injury. Circulating PAF-acetylhydrolase (PAF-AH) hydrolyzes PAF to lyso-PAF. Recently, ROMs have been shown to rapidly and irreversibly inactivate human PAF-AH. Consequently, our study hypothesis was that reduced levels of PAF-AH in severely injured patients would be associated with the development of multiple organ failure (MOF). Over a 16 mo period, 26 patients at known risk for MOF (Injury Severity Score (ISS) > or = 25 or an ISS > 15 with > or = 6 U of blood transfused within the first 6 h) had blood sampled on postinjury days 0, 1, 2, 3, and 5. PAF-AH activity was assessed by measuring the percentage of 3H-labeled PAF hydrolyzed. MOF was defined by a standard score. The mean age of the 26 study patients was 34 +/- 2 yr; 19 (73%) were male. The injury mechanism was blunt in 18 (69%), and the mean ISS was 31 +/- 2. Eight patients (31%) developed MOF. In the MOF patients, plasma PAF-AH activity was significantly lower on the day of injury and remained depressed throughout the ensuing 5 days compared with the non-MOF patients. Reduced PAF-AH activity is associated with the development of postinjury MOF. With the recent molecular cloning of human plasma PAF-AH, repleting this circulating, anti-inflammatory enzyme may represent useful therapy for these high risk patients.
Partrick
D A
DA
Department of Surgery, Denver Health Medical Center, University of Colorado Health Sciences Center 80204, USA.
Moore
E E
EE
Moore
F A
FA
Biffl
W L
WL
Barnett
C C
CC
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D009102:Multiple Organ Failure / Q000201:enzymology* / Q000209:etiology; D010741:Phospholipases A / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D014947:Wounds and Injuries / Q000150:complications*
D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase