Influence of isoprostane F2alpha-III on reflow after myocardial infarction.
OBJECTIVE
To investigate whether the vasoconstrictor isoprostane F2alpha-III (iPF2alpha-III), released during myocardial reperfusion, contributes to the low/no reflow phenomenon observed following acute myocardial infarction (AMI).


RESULTS
Thirteen patients undergoing primary percutaneous coronary intervention (PCI) for AMI had iPF2alpha-III measured by high-performance liquid and gas chromatography-mass spectrometry. Isoprostane F2alpha-III concentrations were significantly higher following PCI than in controls (1.5+/-1.3 vs.16+/-0.06 nM, p < 0.001). Mean iPF2alpha-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, iPF2alpha-III concentrations of 1 microM. From 1 to 10 microM, iPF2alpha-III induced dose-dependent vasoconstriction (p = 0.005) with reduction in coronary flows (f) of 57+/-5% and 31+/-4% (percentage baseline), respectively; (b) SQ29548 1 microM completely reversed the vasoconstrictive effects of iPF2alpha-III 10 microM; (c) SQ29548 1 microM infused during reperfusion following 30 min ischaemia had no effect on CF or infarct volume.


CONCLUSIONS
Concentrations of iPF2alpha-III released into the venous circulation during reperfusion following AMI in humans are significantly lower than those required to diminish coronary flow in the murine heart; increased levels indicate successful reperfusion. Inhibition of iPF2alpha-III has no effect on coronary flow or infarct size in the murine heart, suggesting that iPF2alpha-III alone does not account for the low/no reflow phenomenon observed following AMI.
Greaves
Kim
K
Department of Cardiology, The Cardiovascular Division, King's College London, St. Thomas' Hospital, London, UK.
Dixon
Simon R
SR
Coker
Ivan O'Brien
IO
Mallet
Anthony I
AI
Avkiran
Metin
M
Shattock
Michael J
MJ
Fejka
Martin J
MJ
O'Neill
William W
WW
Senior
Roxy
R
Redwood
Simon
S
Marber
Michael S
MS
D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000097:blood*; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015425:Myocardial Reperfusion / Q000379:methods*; D011446:Prospective Studies; D014665:Vasodilator Agents / Q000378:metabolism*
D028421:Isoprostanes; D014665:Vasodilator Agents; C438786:isoprostane F2alpha III