Increased Formation of the Isoprostanes IPF 2α -I and 8-Epi-Prostaglandin F 2α in Acute Coronary Angioplasty

Abstract

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 F 2 isoprostanes, 8-epi-PGF 2α and IPF 2α -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-PGF 2α [ P =.009] and 466±91 versus 833±153 for IPF 2α -I [ P =.001]) and returned toward preprocedural values by 24 hours (122±18 for 8-epi-PGF 2α and 457±102 for IPF 2α -I). There was a slight increase in urinary 8-epi-PGF 2α 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-PGF 2α and IPF 2α -I levels in patients receiving thrombolytic agents for acute MI. Conclusions Urinary F 2 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.