Reduction of ischemic damage in isolated rat hearts by the potassium channel opener, RP 52891.
Potassium channel activators have been shown to protect ischemic myocardium. We studied the ability of the novel potassium channel activator, RP 52891, to also reduce ischemic damage in isolated globally ischemic rat hearts. RP 52891 (1-100 microM) was given before the hearts were subjected to 25 min of ischemia and 30 min of reperfusion. Before ischemia, RP 52891 reduced contractile function only at the highest concentration (100 microM). Significant reductions in ischemic damage were observed at 3 microM and higher concentrations. RP 52891 improved reperfusion contractile function and reduced lactate dehydrogenase release. Contracture was significantly reduced by RP 52891 during reperfusion. The protective effects of RP 52891 were completely reversed by glyburide and sodium 5-hydroxydecanoate, both blockers of ATP-sensitive potassium channels. Thus, RP 52891 has direct cardioprotective efficacy, which may be related to activation of ATP-sensitive potassium channels.
Grover
G J
GJ
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, NJ 08543-4000.
Dzwonczyk
S
S
Sleph
P G
PG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003652:Decanoic Acids / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D010847:Picolines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D003652:Decanoic Acids; D006880:Hydroxy Acids; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; C061043:aprikalim; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005905:Glyburide