title: 15-F(2t)-isoprostane exacerbates myocardial ischemia-reperfusion injury of isolated rat hearts.
abstract: Reactive oxygen species induce formation of 15-F(2t)-isoprostane (15-F(2t)-IsoP), a specific marker of in vivo lipid peroxidation, which is increased after myocardial ischemia and during the subsequent reperfusion. 15-F(2t)-IsoP possesses potent bioactivity under pathophysiological conditions. However, it remains unknown whether 15-F(2t)-IsoP, by itself, can influence myocardial ischemia-reperfusion injury (IRI). Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit (KH) solution at a constant flow rate of 10 ml/min. 15-F(2t)-IsoP (100 nM), SQ-29548 (1 microM, SQ), a thromboxane receptor antagonist that can abolish the vasoconstrictor effect of 15-F(2t)-IsoP, 15-F(2t)-IsoP + SQ in KH, or KH alone (vehicle control) was applied for 10 min before induction of 40 min of global ischemia followed by 60 min of reperfusion. During ischemia, saline (control), 15-F(2t)-IsoP, 15-F(2t)-IsoP + SQ, or SQ in saline was perfused through the aorta at 60 microl/min. 15-F(2t)-IsoP, 15-F(2t)-IsoP + SQ, or SQ in KH was infused during the first 15 min of reperfusion. Coronary effluent endothelin-1 concentrations were significantly higher in the group treated with 15-F(2t)-IsoP than in the control group during ischemia and also in the later phase of reperfusion (P < 0.05). Infusion of 15-F(2t)-IsoP increased release of cardiac-specific creatine kinase, reduced cardiac contractility during reperfusion, and increased myocardial infarct size relative to the control group. SQ abolished the deleterious effects of 15-F(2t)-IsoP. 15-F(2t)-IsoP exacerbates myocardial IRI and may, therefore, act as a mediator of IRI. 15-F(2t)-IsoP-induced endothelin-1 production during cardiac reperfusion may represent a mechanism underlying the deleterious actions of 15-F(2t)-IsoP.
authors.affiliation: University of British Columbia, Department of Anesthesiology, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Kuo
authors.forename: David V
authors.initials: DV
authors.lastname: Godin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walker
authors.forename: Michelle C Y
authors.initials: MC
authors.lastname: Tao
authors.forename: David M
authors.initials: DM
authors.lastname: Ansley
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D052279:Creatine Kinase, MB Form; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D007527:Isoenzymes; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form