Platelet-activating factor acetylhydrolase prevents myocardial ischemia-reperfusion injury.
BACKGROUND
Platelet-activating factor (PAF) is one of the most potent biological mediators of tissue injury. PAF acetylhydrolase (PAF-AH) is a recently isolated naturally occurring enzyme that hydrolyzes PAF and renders it inactive. We hypothesize that inhibition of PAF with PAF-AH will reduce myocardial ischemia-reperfusion (I/R) injury in vivo.


RESULTS
The coronary ligation model was used in New Zealand white rabbits. The large branch of the marginal coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given either 2 mg/kg of vehicle or of PAF-AH. At the completion of 120 minutes of reperfusion, percentage of necrosis, degree of neutrophil infiltration, and measurements of regional contractility were assessed. Data are expressed as the mean+/-SEM and compared by Student's t test or Mann-Whitney ANOVA. Both groups of animals showed an equivalent area at risk; however, 46.7+/-11% was necrotic in the animal treated with vehicle. In contrast, 20.9+/-7.0% was necrotic in the animals treated with PAF-AH (P<0.05). Systolic shortening and wall thickness were significantly greater in those animals treated with PAF-AH at 15, 30, 60, and 120 minutes of reperfusion (P<0.05). Quantification of neutrophil infiltration showed a 62% reduction in the PAF-AH treated animals compared with those treated with vehicle alone.


CONCLUSIONS
PAF-AH is a potent cardioprotective agent in an in vivo model of I/R injury.
Morgan
E N
EN
Department of Surgery, University of Washington, Seattle, WA 98195, USA.
Boyle
E M
EM
Yun
W
W
Kovacich
J C
JC
Canty
T G
TG
Chi
E
E
Pohlman
T H
TH
Verrier
E D
ED
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D009203:Myocardial Infarction / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010741:Phospholipases A / Q000008:administration & dosage*; D011817:Rabbits
D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase