(Circulation. 1997;95:2492.)
© 1997 American Heart Association, Inc.
Articles |
8-Epi PGF2
Generation During Coronary Reperfusion
A Potential Quantitative Marker of Oxidant Stress In Vivo
the Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia; Philadelphia Biomedical Research Institute, King of Prussia, Pa (S.T.O.); the Department of Cardiothoracic Surgery, Mater Hospital, Dublin, Ireland (J.F.M., A.E.W.); and the Center for Cardiovascular Science, RCSI, Dublin, Ireland (D.J.F.).
Correspondence to Dr G.A. FitzGerald, Center for Experimental Therapeutics, 905 Stellar-Chance Laboratories, 422 Curie Blvd, University of Pennsylvania, Philadelphia, PA 19104. E-mail garret{at}spirit.gcrc.upenn.edu
Abstract
Background Myocardial reperfusion is believed to be associated with free radical injury. However, indexes of oxidative stress in vivo have been limited by their poor specificity and sensitivity. Isoprostanes are stable products of arachidonic acid formed in a nonenzymatic, free radical–catalyzed manner. We have developed a sensitive and specific assay for one of these compounds, 8-epi prostaglandin (PG) F2
.
Methods and Results To address its utility as an index of oxidative stress during coronary reperfusion, we measured urinary levels by gas chromatography/mass spectrometry in a canine model of coronary thrombolysis, in patients with acute myocardial infarction treated with thrombolytic therapy, and in patients after elective coronary artery bypass surgery. Urinary 8-epi PGF2 was unchanged after circumflex artery occlusion in a canine model of coronary thrombolysis (n=13; 437.2±56.4 versus 432.7±55.2 pmol/mmol creatinine) but increased significantly (P<.05) immediately after reperfusion (553.8±64.7 pmol/mmol). Urinary levels were increased (P<.001) in patients (n=12) with acute myocardial infarction given lytic therapy (265.8±40.8 pmol/mmol) compared with age-matched control subjects (n=20; 91.5±11.8 pmol/mmol) and patients with stable coronary disease (n=20; 95.7±6.3 pmol/mmol). Preoperative levels rose from 113.2±11.8 to 248.2±86.3 pmol/mmol at 30 minutes into revascularization to 332.2±82.6 pmol/mmol by 15 minutes after global myocardial reperfusion (P<.05) and dropped to 181.2±50.4 pmol/mmol at 30 minutes and 120.2±9.9 pmol/mmol at 24 hours after bypass surgery (n=5). Corresponding changes in spin adduct formation, found with electron paramagnetic resonance, were noted in 2 patients.
Conclusions These data support the hypothesis that free radical generation occurs during myocardial reperfusion. Measurement of isoprostane production may serve as a noninvasive index of oxidative stress.
Key Words: reperfusion • free radicals • prostaglandins
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