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(Circulation. 1997;96:3314-3320.)
© 1997 American Heart Association, Inc.
Articles |
Increased Formation of the Isoprostanes IPF2
-I and 8-Epi-Prostaglandin F2 in Acute Coronary Angioplasty
Evidence for Oxidant Stress During Coronary Reperfusion in Humans
From The Center for Experimental Therapeutics, University of Pennsylvania (M.P.R., N.D., J.A.L., G.A.F.); Institute of Cardiology, Hopital Laval, Quebec City, Canada (L.R.); Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology (J.R.), Melbourne; and Department of Cardiology, St James Hospital, Dublin, Ireland (P.O.C., P.C.).
Background The role of oxidant stress in cardiac ischemia/reperfusion injury in humans remains controversial. This is due, in part, to the limitations of available indices of oxidant stress in vivo. Isoprostanes are stable, free radical–catalyzed products of arachidonic acid. We assessed their formation in patients undergoing coronary reperfusion via percutaneous transluminal coronary angioplasty (PTCA).
Methods and Results We developed specific, mass spectrometry
assays for two structurally distinct F2 isoprostanes,
8-epi-PGF2 and IPF2-I. Urine samples for
isoprostane determination were collected in patients undergoing
coronary arteriography (n=11), elective PTCA (n=15), and
angiography after thrombolysis for acute myocardial
infarction (MI) (n=10). Urinary levels (pmol/mmol
creatinine) of both isoprostanes were markedly increased
from baseline in the first 6 hours after PTCA for acute MI (105±17.8
versus 230±66 for 8-epi-PGF2 [P=.009]
and 466±91 versus 833±153 for IPF2-I
[P=.001]) and returned toward preprocedural values by
24 hours (122±18 for 8-epi-PGF2 and 457±102 for
IPF2-I). There was a slight increase in urinary
8-epi-PGF2 levels (64.7±9.5 versus 84.9±10.6;
P=.02) after diagnostic coronary
arteriography and elective PTCA (88.7±7.5 versus 114.3±16.1;
P=.01). A striking correlation was observed
(r=.68, P<.0001; n=33) between urinary
8-epi-PGF2 and IPF2-I levels in patients
receiving thrombolytic agents for acute MI.
Conclusions Urinary F2 isoprostane levels are elevated in patients after treatments resulting in reperfusion for acute MI. These findings provide evidence consistent with increased oxidant stress in vivo in this setting. Measurement of urinary isoprostanes may offer a noninvasive approach to the assessment of oxidant stress and the efficacy of antioxidant therapies in these syndromes.
Key Words: oxidant stress • lipids • angioplasty
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