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: Zhengyuan Xia, Kuo-Hsing Kuo, David V Godin, Michael J Walker, Michelle C Y Tao, David M Ansley
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 289 Issue 4 Pg. H1366-72 (Oct 2005) ISSN: 0363-6135 [Print] United States
• PMID: 15937102 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin-1
• Isoenzymes
• Vasoconstrictor Agents
• 8-epi-prostaglandin F2alpha
• Dinoprost
• Creatine Kinase
• Creatine Kinase, MB Form

Topics

• Animals
• Blood Pressure (physiology)
• Creatine Kinase (metabolism)
• Creatine Kinase, MB Form
• Dinoprost (analogs & derivatives, pharmacology)
• Endothelin-1 (metabolism)
• Heart (drug effects, physiology)
• In Vitro Techniques
• Isoenzymes (metabolism)
• Male
• Myocardial Infarction (metabolism, pathology, physiopathology)
• Myocardial Reperfusion Injury (metabolism, pathology, physiopathology)
• Myocardium (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Vasoconstrictor Agents (pharmacology)