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(Circulation. 2001;104:2210.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Roles of Prostaglandin I₂ and Thromboxane A₂ in Cardiac Ischemia-Reperfusion Injury

A Study Using Mice Lacking Their Respective Receptors

Chun-Yang Xiao, PhD; Akiyoshi Hara, PhD; Koh-ichi Yuhki, MS; Takayuki Fujino, MD; Hong Ma, MD; Yuji Okada, MD; Osamu Takahata, MD; Takehiro Yamada, MS; Takahiko Murata, BS; Shuh Narumiya, MD; Fumitaka Ushikubi, MD

From the Department of Pharmacology, Asahikawa Medical College, Asahikawa (C-Y.X., A.H., K.Y., T.F., H.M., Y.O., O.T., T.Y., F.U.), and the Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto (T.M., S.N.), Japan.

Correspondence to Fumitaka Ushikubi, MD, Department of Pharmacology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan. E-mail ushikubi{at}asahikawa-med.ac.jp

Background— Prostaglandin (PG) I₂ and thromboxane (TX) A₂, the most common prostanoids in the cardiovascular system, are produced abundantly during cardiac ischemia/reperfusion (I/R); their roles in I/R injury, however, remain undetermined. We intended to clarify these roles of PGI₂ and TXA₂ using mice lacking the PGI₂ receptor, IP^-/- mice, or the TXA₂ receptor, TP^-/- mice.

Methods and Results— The left anterior descending coronary artery was occluded for 1 hour and then reperfused for 24 hours. The size of myocardial infarct in IP^-/- mice was significantly larger than that in wild-type mice, although the size of the area at risk was similar between the 2 groups of mice. In contrast, there was no such difference between TP^-/- and wild-type mice. To further determine whether PGI₂ and TXA₂ act directly on the cardiac tissue or indirectly through their action on blood constituents, we perfused excised heart according to the Langendorff technique. The isolated heart was then subjected to global ischemia followed by reperfusion. In IP^-/- mice, developed tension and coronary flow rate during reperfusion were significantly lower and release of creatine kinase was significantly higher than those in wild-type mice. There were no such differences, however, between TP^-/- and wild-type mice.

Conclusions— PGI₂, which was produced endogenously during cardiac I/R, exerts a protective effect on cardiomyocytes independent of its effects on platelets and neutrophils. In contrast, TXA₂ has little role in the cardiac I/R injury.

Key Words: prostaglandins • thromboxane • ischemia • reperfusion • myocardium

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