Influence of isoprostane F2α-III on reflow after myocardial infarction

Aims To investigate whether the vasoconstrictor isoprostane F2alphaIII (iPF(2alpha)-III), released during myocardial reperfusion, contributes to the low/no reflow phenomenon observed following acute myocardial infarction (AMI). Methods and results Thirteen patients undergoing primary percutaneous coronary intervention (PCI) for AMI had iPF(2alpha)-III measured by high - performance liquid and gas chromatography-mass spectrometry. Isoprostane F-2alpha-III concentrations were significantly higher following PCI than in controls (1.5 +/- 1.3 vs. 16 +/- 0.06 nM, p < 0.001). Mean iPF(2alpha)-III concentration correlated positively with ST-segment resolution at 90 min (R = 0.62, p < 0.05). In the isolated murine heart: (a) coronary vasoconstriction occurred at, or above, iPF(2alpha)-III concentrations of 1 muM. From 1 to 10 muM, iPF(2alpha)-III induced dose-dependent vasoconstriction (p = 0.005) with reduction in coronary flows (CF) of 57 +/- 5% and 31 +/- 4% (percentage baseline), respectively; (b) SQ29548 1 muM completely reversed the vasoconstrictive effects of iPF(2alpha)-III 10 muM; (c) SQ29548 1 muM infused during reperfusion following 30 min ischaemia had no effect on CF or infarct volume. Conclusion Concentrations of iPF(2alpha)-III released into the venous circulation during reperfusion following AMI in humans are significantly tower than those required to diminish coronary flow in the murine heart; increased levels indicate successful reperfusion. Inhibition of iPF(2alpha)-III has no effect on coronary flow or infarct size in the murine heart, suggesting that iPF(2alpha)-III alone does not account for the low/no reflow phenomenon observed following AMI. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.