KATP channel modulators increase survival rate during coronary occlusion-reperfusion in anaesthetized rats.
We investigated the effect of ATP-sensitive K+ channel (KATP) openers (pinacidil and cromakalim), and a KATP blocker (glibenclamide) on reperfusion-induced arrhythmias in pentobarbitone-anaesthetized rats. Arrhythmias were induced by reperfusion following a 6 min ligation of the left main coronary artery. Rats were pretreated with pinacidil (0.1 or 0.3 mg/kg), or cromakalim (28 or 56 micrograms/kg), or glibenclamide (5 mg/kg), or vehicle. Pinacidil and cromakalim produced dose-related reductions in blood pressure. Pinacidil (0.1 mg/kg) and cromakalim (56 micrograms/kg) significantly decreased the incidence of reperfusion-induced ventricular fibrillation and increased survival. Glibenclamide did not decrease ventricular fibrillation incidence, yet improved survival by increasing the possibility of recovery from ventricular fibrillation. The present study suggests that both opening and blocking KATP channels may increase survival during coronary occlusion and reperfusion in anaesthetized rats.
Baczkó
I
I
Department of Pharmacology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Leprán
I
I
Papp
J G
JG
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000401:mortality; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality; D019806:Cromakalim; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000401:mortality; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D002121:Calcium Channel Blockers; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide