Effect of the potassium channel opener EMD 56431 on globally ischemic rat hearts.
The effect of the ATP-sensitive potassium channel opener EMD 56431 on coronary vasodilation and cardioprotection in isolated rat hearts was investigated. EMD 56431 caused a significant increase in pre-ischemic coronary flow. Time to contracture and reperfusion function were significantly increased at 3, 10 and 30 microM concentrations. LDH release was significantly reduced at 10 and 30 microM concentrations. 1 microM glyburide completely abolished the protective effects found with 10 microM EMD 56431. When given during reperfusion only, 10 microM EMD 56431 showed no cardioprotection. Thus, EMD 56431 appeared to reduce the severity of ischemia/reperfusion injury. The vasorelaxant versus cardioprotective effects for EMD 56431 are similar to other potassium channel openers, such as cromakalim.
Sargent
C A
CA
Bristol-Myers Squibb Pharmaceutical Research Institute, Department of Pharmacology, Princeton, NJ 08543.
Dzwonczyk
S
S
Grover
G J
GJ
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D015221:Potassium Channels / Q000187:drug effects*; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011728:Pyridones; D014665:Vasodilator Agents; C078701:EMD 56431; D007770:L-Lactate Dehydrogenase; D005905:Glyburide