15-F2t-isoprostane exacerbates myocardial ischemia-reperfusion injury of isolated rat hearts

• Published in: American journal of physiology. Heart and circulatory physiology 2005-10, Vol.289 (4), p.H1366
• Main Authors: Xia, Zhengyuan, Kuo, Kuo-Hsing, Godin, David V, Walker, Michael J, Tao, Michelle C. Y, Ansley, David M
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00042.2005

1 Centre for Anesthesia and Analgesia, Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver; 3 Department of Anatomy and Histology, University of Northern British Columbia, Prince George, British Columbia, Canada; and 2 Anesthesiology Research Laboratory, Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China Submitted 14 January 2005 ; accepted in final form 17 May 2005 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 µM, 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 µl/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. ischemia-reperfusion injury; SQ-29548; endothelin-1 Address for reprint requests and other correspondence: D. M. Ansley, Univ. of British Columbia, Dept. of Anesthesiology, Rm. 3200, 3rd Floor JPP, 910 West 10th Ave., Vancouver, BC, Canada V5Z 4E3 (E-mail: david.an