Effects of SEA0400, a novel inhibitor of the Na+/Ca2+ exchanger, on myocardial stunning in anesthetized dogs.
Activation of the Na+/Ca2+ exchanger may contribute to Ca2+ overload during reperfusion after transient ischemia. We examined the effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion injury (myocardial stunning). Myocardial stunning was induced by a 15-min occlusion of the left anterior descending coronary artery followed by a 4-h reperfusion in anesthetized open-chest dogs. Reperfusion gradually restored myocardial percent segment shortening but remained depressed during a 4-h reperfusion period. A bolus intravenous injection of SEA0400 (0.3 or 1.0 mg/kg), given 1 min before reperfusion, improved significantly the recovery of percent segment shortening in the ischemic/reperfused myocardium. SEA0400 did not affect the hemodynamics and electrocardiogram parameters. In addition, SEA0400 did not affect reperfusion-induced change in coronary blood flow. These results suggest that the Na+/Ca2+ exchanger is involved in the stunned myocardium of dogs after reperfusion, and that SEA0400 has a protective effect against myocardial stunning in dogs.
Takahashi
Teisuke
T
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan. teisuke.takahashi@po.rd.taisho.co.jp
Takahashi
Kenzo
K
Onishi
Michihito
M
Suzuki
Taizo
T
Tanaka
Yu
Y
Ota
Tomomi
T
Yoshida
Shigeru
S
Nakaike
Shiro
S
Matsuda
Toshio
T
Baba
Akemichi
A
D000758:Anesthesia; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications; D017682:Myocardial Stunning / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010647:Phenyl Ethers / Q000494:pharmacology*; D011897:Random Allocation; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000814:Aniline Compounds; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger