Dose-related shortening of ventricular tachycardia cycle length after administration of the KATP channel opener bimakalim in a 4-day-old chronic infarct anesthetized pig model.

Potassium channel openers are known to act on potassium ATP-dependent channels in cardiac tissue. Such agents may exacerbate acceleration of acute ischemia-induced ventricular repolarization and aggravate arrhythmias. To test whether activation of K( ATP) channels during the healing period of myocardial infarction (MI) can still influence the electrophysiologic properties and the type of inducible arrhythmias, we investigated the effects of bimakalim (BIM) on sustained ventricular tachycardia (VT) 4 days after ligation of the left anterior descending (LAD) coronary artery in pigs. Programmed stimulation was performed to elicit VT prior to and after intravenous (IV) BIM. Combination monophasic action potential (MAP)/PACING catheters were used to enable simultaneous ventricular MAP recording and pacing. Ventricular effective refractory period (ERP) and MAP duration determined at 50% and 90% repolarization were measured prior to and after BIM. After completion of baseline measurements, BIM was consecutively given at 0.5, 1, and 3 mg/kg bolus followed by 0.025, 0.05, and 0.1 mg/kg per minute maintenance infusion, respectively. From a total of 23 pigs subjected to LAD ligation, 4 animals succumbed to infarction and the remaining 19 animals were studied by programmed stimulation. Only animals that exhibited reproducible and hemodynamically stable monomorphic VTs during control stimulation were selected for evaluation (n = 14). After the first, second, and third dose of BIM, the mean VT rate was increased by 6%, 14% (P <. 01), and 47% (P < .001) compared to control values, respectively. Ventricular ERP and repolarization were significantly shortened only by the second and third dose of BIM. Of 14 pigs receiving the highest BIM dosage, 3 revealed polymorphic VTs degenerating into ventricular fibrillation (VF). Our data suggest that high BIM doses may lead to faster and more aggressive pacing-induced reentrant VTs after subacute MI. This is consistent with the drug-induced acceleration of ventricular repolarization with shortening of MAP duration and refractoriness.

Assessment of local atrial repolarization in a porcine acetylcholine model of atrial flutter and fibrillation.

OBJECTIVES: Progressive electrical alternans followed by conduction block and fibrillatory conduction have been suggested to precede disorganization of atrial flutter (Afl) to atrial fibrillation (AF). The purpose of the present study was to investigate patterns of local repolarization in the high and low right atrium to determine the site with pronounced propensity to action potential disorganization during Afl and AF. METHODS: Combination pacing/recording contact monophasic action potential (MAP) catheters were utilized to evaluate repolarization from the upper and low atrial endocardium in 16 pigs. To induce sustained atrial flutter (Afl) or fibrillation (AF), programmed atrial stimulation was carried out prior to and during intravenous acetylcholine (ACh) infusion at a dosage rate of 2.7 mg/min. Atrial repolarization was measured at 30, 50, and 90% of total MAP duration. RESULTS: Two main types of atrial MAPs were distinguished: MAPs originated from high atrial regions showing a prominent notch and longer duration and MAPs recorded from the lower atrium displaying a much slower slope of phase I repolarization and shorter duration. Control stimulation did not elicit any significant atrial tachyarrhythmias. After ACh all animals developed reproducibly induced sustained and non-sustained whole Afl or AF during programmed stimulation. A total of 40 sustained arrhythmia episodes were selected for evaluation: fourteen episodes of primary AF and 26 episodes of Afl. Whole Afl and AF in all animals were associated with MAPs of almost regular morphology in lower parts of atrium and disorganized activation in higher atrial regions. ACh significantly reduced (P < 0.001) both high and low atrial effective refractory periods as well as MAP duration determined at 30, 50, and 90% repolarization. CONCLUSIONS: ACh facilitated the induction of Afl more than AF in this experimental model. MAPs recorded from high atrial regions revealed discordant repolarization during Afl or AF, whereas low atrial MAPs maintained their baseline regular morphology. These findings may help expand knowledge about mechanisms underlying instability and perpetuation of these arrhythmias.