The effects of potassium-ATP channel modulation on ventricular fibrillation and defibrillation in the pig heart.
BACKGROUND
Drugs acting on the cardiac ATP-sensitive potassium (K-ATP) channels may modulate responses to ischaemia and arrhythmogenesis. We investigated the effects of K-ATP channel modulation on frequency patterns of ventricular fibrillation (VF) and on defibrillation threshold (DFT).


RESULTS
Each group of 24 pigs randomly received intravenous levcromakalim (LKM) 40 microgram/kg (K-ATP agonist), glibenclamide (Glib) 20 mg/kg (K-ATP antagonist), saline or vehicle. Firstly, QTc interval was measured before and after drug. VF was then induced by endocardial stimulation and its power spectra and dominant frequencies over 15 min determined by fast Fourier transformation. Secondly, transthoracic DFT was determined (step-up/step-down protocol) before and after each drug. LKM reduced QTc interval (e.g., lead II, 354-321 ms, P<0.05) and increased the dominant VF frequency between 6 and 8 min (9.5+/-0.5 Hz at 6.5 min compared with 7.2+/-0.6 Hz (saline), 7.4+/-0.8 Hz (vehicle), 6.8+/-0.5 Hz (Glib), P=0.03). LKM reduced (to 57.2+/-2.1 mmHg) and Glib increased (to 107.8+/-6.1) mean arterial BP compared with saline (80.3+/-5.6) and vehicle (87. 6+/-7.1; P<0.01). There was no significant difference in defibrillation threshold energy, current or voltage, after any drug.


CONCLUSIONS
Activation of K-ATP channels reduced blood pressure and QTc interval. The lack of major effect on VF dominant frequency and DFT of either LKM or Glib suggests that prior administration of similar drugs to patients should not prejudice outcome from VF cardiac arrest.
Harbinson
M T
MT
Regional Medical Cardiology Centre, Royal Victoria Hospital, BT12 6BA, N. Ireland, Belfast, UK.
Allen
J D
JD
Adgey
A A
AA
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology*; D004594:Electrophysiology; D005583:Fourier Analysis; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D005905:Glyburide