Effects of glibenclamide and nicorandil on cardiac function during ischemia and reperfusion in isolated perfused rat hearts.
We examined influences of a blocker (glibenclamide) and an opener (nicorandil) of the ATP-sensitive potassium (KATP) channel on extracellular K concentration [( K+]e), as well as the myocardial function and metabolites during global ischemia and reperfusion in Langendorff-perfused rat heart preparation. In control hearts, [K+]e began to rise 20 s after the onset of ischemia up to an initial peak (8.3 +/- 0.3 mM) at 2.5 +/- 0.7 min, then fell to 6.0 +/- 0.8 mM after 8.2 +/- 0.7 min, and then rose progressively to 14.6 +/- 0.8 mM at the end of 30 min of ischemia. Glibenclamide (50 microM) reduced the initial peak of [K+]e to 7.2 +/- 0.3 mM (P less than 0.01), and nicorandil (200 microM) increased it to 9.4 +/- 0.6 mM (P less than 0.01). There were no significant differences in [K+]e values among all groups at the end of ischemia. During ischemia, nicorandil decreased the time to mechanical arrest from 1.9 +/- 0.1 min to 1.5 +/- 0.1 min, whereas it was increased by glibenclamide to 2.7 +/- 0.4 min. In control hearts, the time to onset of ischemic contracture was 14.7 +/- 1.8 min. Nicorandil delayed onset of contracture and glibenclamide accelerated it. Thus we have confirmed that some part of the early increase in [K+]e during ischemia is attributable to K+ efflux through the KATP channel in our model, and opening of the KATP channel may contribute to a rapid reduction of the contractility of the ischemic myocardium that subsequently protects the myocardium against further ischemic injury.
Mitani
A
A
Division of Cardiovascular Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kinoshita
K
K
Fukamachi
K
K
Sakamoto
M
M
Kurisu
K
K
Tsuruhara
Y
Y
Fukumura
F
F
Nakashima
A
A
Tokunaga
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D016277:Ventricular Function, Left
D015221:Potassium Channels; D009536:Niacinamide; D020108:Nicorandil; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide