KATP channel modulation in working rat hearts with coronary occlusion: Effects of cromakalim, cicletanine, and glibenclamide

Péter Ferdinandy, Zoltán Szilvássy, Marie T. Droy-Lefaix, Thierry Tarrade, Matyas Koltai

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Objectives: 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 μM cromakalim, an opener of KATP; 3–60 μM cicletanine; and 0.1–10 μM glibenclamide, a blocker of KATP, respectively. Results: All concentrations of cicletanine, similarly to 0.1–10 μM 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 μM) and cromakalim (10 and 60 μM) significantly reduced the incidence of reperfusion-induced VF; however, 60 μM 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 μM) did not significantly affect cardiac performance, but it did abolish the anti-ischemic effect of cromakalim (1–10 μM) and cicletanine (60 μM). Glibenclamide suppressed the anti-arrhythmic effect of 10 and 60 μM 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.

Original languageEnglish
Pages (from-to)781-787
Number of pages7
JournalCardiovascular research
Issue number5
Publication statusPublished - Nov 1995



  • Arrhythmias
  • Cicletanine
  • Heart
  • Myocardial function
  • Myocardial ischemia
  • Potassium channel openers
  • Rat
  • Reperfusion
  • Sulphonylureas

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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