INCREASED FORMATION OF THE ISOPROSTANES IPF2-ALPHA-I AND 8-EPI-PROSTAGLANDIN F2-ALPHA IN ACUTE CORONARY ANGIOPLASTY - EVIDENCE FOR OXIDANT STRESS DURING CORONARY REPERFUSION IN HUMANS

Background The role of oxidant stress in cardiac ischemia/reperfusion injury in humans remains controversial. This is due, in part, to the l imitations of available indices of oxidant stress in vivo. Isoprostane s are stable, free radical-catalyzed products of arachidonic acid. We assessed their formation in patients undergoing coronary reperfusion v ia percutaneous transluminal coronary angioplasty (PTCA). Methods and Results We developed specific, mass spectrometry assays for two struct urally distinct F-2 isoprostanes, 8-epi-PGF(2 alpha), and IPF2 alpha-I . Urine samples for isoprostane determination were collected in patien ts undergoing coronary arteriography (n = 11), elective PTCA (n = 15), and angiography after thrombolysis for acute myocardial infarction (M I) (n = 10). Urinary levels (pmol/mmol creatinine) of both isoprostane s were markedly increased from baseline in the first 6 hours after PTC A for acute MI (105 +/- 17.8 versus 230 +/- 66 for 8-epi-PGF(2 alpha) [P = .009] and 466 +/- 91 versus 833 +/- 153 for IPF2 alpha-I [P = .00 1]) and returned toward preprocedural values by 24 hours (122 +/- 18 f or 8-epi-PCF2 alpha and 457 +/- 102 for IPF2 alpha-I), There was a sli ght increase in urinary 8-epi-PGF(2 alpha) levels (64.7 +/- 9.5 versus 84.9 +/- 10.6 P = .02) after diagnostic coronary arteriography and el ective 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-PGF(2 alpha) and IPF2 alpha-I levels in patients receiving throm bolytic agents for acute MI, Conclusions Urinary F-2 isoprostane level s are elevated in patients after treatments resulting in reperfusion f or acute MI, These findings provide evidence consistent with increased oxidant stress in vivo in this setting. Measurement of urinary isopro stanes may offer a noninvasive approach to the assessment of oxidant s tress and the efficacy of antioxidant therapies in these syndromes.