Y-26763 protects the canine heart from a stunning injury through opening of the KATP channels

• Published in: European journal of pharmacology 1997-04, Vol.323 (2-3), p.197-204
• Main Authors: FUKUNARI, A, MIYAI, H, SHINAGAWA, K, KAWAHARA, K, NAKAJIMA, T
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Antihypertensive Agents - pharmacology; Benzopyrans - pharmacology; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Cardiovascular system; Dogs; Female; Glyburide - pharmacology; Hemodynamics - drug effects; Male; Medical sciences; Miscellaneous; Myocardial Stunning - physiopathology; Myocardial Stunning - prevention & control; Nifedipine - pharmacology; Pharmacology. Drug treatments; Potassium Channels - drug effects
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)00035-6

The present study describes the protective effects of the ATP-sensitive K+ (KATP) channel opener Y-26763 ((-)-(3S,4R-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl -2H-1-benzopyran-3-ol), on a model of reversible ischemia/reperfusion injury ('stunned' myocardium). Stunning was caused by 10-min occlusion of the left circumflex coronary artery followed by 3-h reperfusion in pentobarbital anesthetized beagle dogs. This procedure reduced by over 80% myocardial segment function measured by sonomicrometry in control preparations. Y-26763, administered 10 min before the left circumflex coronary artery occlusion, at a dose (3 micrograms/kg, i.v.) lacking significant systemic hemodynamic effects, produced a rapid and marked (80%) recovery of the shortening of the ischemic segment. By contrast, nifedipine (1 microgram/kg plus 0.2 microgram/kg per min, i.v.) did not ameliorate postischemic function. Glibenclamide, administered before Y-26763 at a dose (0.3 mg/kg, i.v.) that did not affect adversely hemodynamics and stunning injury negated the beneficial action of Y-26763. However, glibenclamide failed to do so when administered 2 min before starting reperfusion. The ischemia/reperfusion areas, which were measured by digital image analysis with NIH image software, were similar among experimental groups. Overall, these results indicate that Y-26763 protects the canine myocardium from reversible ischemia/reperfusion injury, probably through activation of myocardial KATP channels which appear to be involved in affording protection during the ischemic insult and not at the reperfusion.