(Circulation. 2000;102:1007.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Oxidant Stress and Aspirin-Insensitive Thromboxane Biosynthesis in Severe Unstable Angina
From the Departments of Medicine and Aging (F. Cipollone, P.P., M.P., G.D., F. Cuccurullo, C.P.) and Biomedical Sciences (T.B.), University of Chieti "G. D’Annunzio" School of Medicine, Chieti, Italy; Department of Pharmacology (G.C.), Catholic University School of Medicine, Rome, Italy; and the Division of Cardiology (D. Di G.), "F. Renzetti" Hospital, Lanciano, Italy.
Correspondence to Carlo Patrono, MD, Dipartimento di Medicina e Scienze dell’Invecchiamento, Università degli Studi "G. D’Annunzio," Via dei Vestini 31, 66013 Chieti, Italy. E-mail cpatrono{at}unich.it
Background—Unstable angina is
associated with enhanced lipid peroxidation and reduced antioxidant
defenses. We have previously reported aspirin failure in the
suppression of enhanced thromboxane (TX) biosynthesis in a
subset of episodes of platelet activation in this setting. We
tested the hypothesis that the in vivo formation of the
F2-isoprostane 8-iso-prostaglandin
(PG)F2
, a bioactive product of
arachidonic acid peroxidation, is enhanced in unstable
angina and contributes to aspirin-insensitive TX biosynthesis.
Methods and Results—Urine samples were obtained from patients
with unstable angina (n=32), stable angina (n=32), or variant angina
(n=4) and from 40 healthy subjects for the measurement of
immunoreactive 8-iso-PGF2 and
11-dehydro-TXB2. 8-Iso-PGF2 excretion was
significantly higher in patients with unstable angina (339±122 pg/mg
creatinine) than in matched patients with stable angina
(236±83 pg/mg creatinine, P=0.001) and
control subjects (192±71 pg/mg creatinine,
P<0.0001). In patients with unstable angina,
8-iso-PGF2 was linearly correlated with
11-dehydro-TXB2 excretion (
=0.721,
P<0.0001) and inversely correlated with plasma vitamin
E (=-0.710, P=0.004). Spontaneous myocardial
ischemia in patients with variant angina or ischemia
elicited by a stress test in patients with stable angina was not
accompanied by any change in 8-iso-PGF2 excretion, thus
excluding a role of ischemia per se in the induction of
increased F2-isoprostane production.
Conclusions—These findings establish a putative biochemical link between increased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of antioxidants in this setting.
Key Words: angina • aspirin • isoprostanes • thromboxane • oxidant stress
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