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Cyclooxygenase-1 Mediates the Final Stage of Morphine-Induced Delayed Cardioprotection in Concert With Cyclooxygenase-2

Xiaojing Jiang, MD^_*, Enyi Shi, MD, PhD, Yoshiki Nakajima, MD, PhD^_*, Shigehito Sato, MD^_*,_*, Koji Ohno, PhD and Hui Yue, MD^_*

^_* Department of Anesthesiology, Hamamatsu University School of Medicine, Hamamatsu, Japan
First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine, Hamamatsu, Japan.

View larger version (27K): [in a new window]   Figure 1 Experimental groups and protocol. IN = indomethacin; IP = intraperitoneal; M = morphine; NS = NS-398; SC = SC-560.

View larger version (19K): [in a new window]   Figure 2 Measurement of myocardial region at risk in all experimental groups. The region at risk is expressed as a percentage of the weight of left ventricle. Open circles represent individual mice, whereas solid circles represent mean ± SEM. There was no significant difference among the 13 groups. IN = indomethacin; M = morphine; NS = NS-398; SC = SC-560.

View larger version (21K): [in a new window]   Figure 3 Measurement of myocardial infarct size in all experimental groups. The infarct size is expressed as a percentage of the region at risk. Open circles represent individual mice, whereas solid circles represent mean ± SEM. IN = indomethacin; IP = intraperitoneal; M = morphine; NS = NS-398; SC = SC-560.

View larger version (22K): [in a new window]   Figure 4 Myocardial content of prostaglandin (PG)E2 and 6-keto-PGF1-alpha after morphine (M) pretreatment. Data are mean ± SEM. IN = indomethacin; NS = NS-398; SC = SC-560. *p < 0.05 vs. control; p < 0.05 vs. M 48 h; p < 0.05 vs. M 24 h.

View larger version (23K): [in a new window]   Figure 5 Expression of cyclooxygenase (COX)-2 in the membranous fraction of myocardium. (A) Representative Western blots illustrating COX-2 expression. (B) Densitometric quantification of COX-2 protein expressed as a percentage of the average value of control mice. Data are mean ± SEM. M = morphine. *p < 0.05 vs. control.

View larger version (25K): [in a new window]   Figure 6 Expression of cyclooxygenase (COX)-1 in the membranous fraction of myocardium. (A) Representative Western blots showing COX-1 expression. (B) Densitometric quantification of COX-1 protein expressed as a percentage of the average value of control mice. Data are mean ± SEM. M = morphine. *p < 0.05 vs. control.