Cardioprotective actions of potassium channel openers. Eur Heart J 1994 Aug;15 Suppl C:89-94
Date
08/01/1994Pubmed ID
7995278DOI
10.1093/eurheartj/15.suppl_c.89Scopus ID
2-s2.0-0028000768 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
The potential cardioprotective effect of two pure potassium channel openers, bimakalim (EMD 52692) and aprikalim (RP 52891), on myocardial ischaemia/reperfusion injury was investigated in barbital-anaesthetized dogs. In a model of reversible ischaemia/reperfusion injury, administration of bimakalim as an intravenous bolus prior to ischaemia or administration of a non-hypotensive dose of aprikalim as a constant intravenous infusion resulted in a reduction in reperfusion contractile dysfunction (myocardial 'stunning') produced by a single 15-min coronary artery occlusion. Administration of aprikalim only during the reperfusion period had no beneficial effect. Similarly, in a model of irreversible ischaemia/reperfusion injury (90 min of coronary artery occlusion followed by 5 h of reperfusion), intravenous infusion of bimakalim at a dose which reduced aortic blood pressure approximately 15-20 mmHg or infusion of aprikalim at a non-hypotensive dose throughout the entire experiment produced a significant reduction in myocardial infarct size. A protective effect of bimakalim was not observed when it was administered during the reperfusion period only. In both the stunned myocardium model as well as the infarcted myocardium model, the beneficial effects of the potassium channel openers could not be attributed to differences in the traditional determinants of the extent of ischaemia/reperfusion injury; area at risk size, oxygen consumption, or collateral blood flow. Furthermore, the anti-ischaemic actions of the potassium channel openers were blocked by pre-treatment with the ATP-dependent potassium (KATP) channel antagonist, glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Author List
Auchampach JA, Maruyama M, Gross GJAuthor
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBenzopyrans
Dihydropyridines
Disease Models, Animal
Dogs
Female
Glyburide
Male
Myocardial Infarction
Myocardial Stunning
Picolines
Potassium Channel Blockers
Potassium Channels
Pyrans
Vasodilator Agents