KATP channel modulation in working rat hearts with coronary occlusion: effects of cromakalim, cicletanine, and glibenclamide.
OBJECTIVE
We studied the effects of ATP-sensitive potassium channel (KATP) modulation on ischemic cardiac performance and reperfusion-induced ventricular fibrillation (VF), and assessed the contribution of KATP to the cardioprotective and anti-arrhythmic effect of the anti-hypertensive drug cicletanine.


METHODS
Isolated working rat hearts, subjected to a 10-min coronary occlusion followed by reperfusion, were perfused in the presence of vehicle, 0.1-60 microM cromakalim, an opener of KATP; 3-60 microM cicletanine; and 0.1-10 microM glibenclamide, a blocker of KATP, respectively.


RESULTS
All concentrations of cicletanine, similarly to 0.1-10 microM cromakalim, attenuated ischemia-induced deterioration of aortic flow, left ventricular developed pressure, and left ventricular end-diastolic pressure. In contrast to cromakalim, cicletanine did not increase coronary flow. Cicletanine (60 microM) and cromakalim (10 and 60 microM) significantly reduced the incidence of reperfusion-induced VF; however, 60 microM cromakalim triggered VF during ischemia. Lower concentrations of cromakalim and cicletanine did not produce an anti-arrhythmic effect. Cardiac functional parameters were concentration dependently worsened by glibenclamide, and the drug did not change the incidence of VF. Glibenclamide (0.1 microM) did not significantly affect cardiac performance, but it did abolish the anti-ischemic effect of cromakalim (1-10 microM) and cicletanine (60 microM). Glibenclamide suppressed the anti-arrhythmic effect of 10 and 60 microM cromakalim; however, it did not affect the anti-arrhythmic effect of cicletanine.


CONCLUSIONS
(i) The anti-ischemic but not the anti-arrhythmic effect of cicletanine may involve opening of KATP. (ii) opening of KATP attenuates, inhibition of the channel exacerbates functional consequences of coronary occlusion, and (iii) KATP opening attenuates reperfusion-induced VF, but it triggers ischemia-induced VF. KATP blocking does not affect VF.
Ferdinandy
P
P
Department of Physiology, Albert Szent-Györgyi University Medical School, Szeged, Hungary. peter@biochem.szote.u-szeged.hu
Szilvássy
Z
Z
Droy-Lefaix
M T
MT
Tarrade
T
T
Koltai
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D015221:Potassium Channels; D011725:Pyridines; D011758:Pyrroles; D019806:Cromakalim; C038068:cicletanine; D005905:Glyburide