Induction of electrical heterogeneity impairs ventricular defibrillation: an effect specific to regional conduction velocity slowing.
BACKGROUND
This study determined whether dispersion of conduction velocity, refractoriness, or excitability increases biphasic shock defibrillation energy requirements (DERs).


RESULTS
Twenty-four swine were instrumented with a mid-LAD perfusion catheter for regional infusion of lidocaine 0.75 mg. kg(-1). h(-1) (n=7), low-dose d-sotalol (0.16 mg. kg(-1). h(-1)) (n=4), high-dose d-sotalol (0.5 mg. kg(-1). h(-1)) (n=6), or saline (n=7). Effective refractory periods (ERPs) were determined at 5 myocardial sites, and regional conduction velocity was determined in LAD-perfused and -nonperfused regions. Regional lidocaine infusion increased DER values by 84% (P=0.008) and slowed conduction velocity by 23% to 35% (P<0.01) but did not affect ERP. Conversely, regional low- and high-dose d-sotalol infusion did not alter DER values or conduction velocity but increased regional ERP by 14% to 17% (P<0.001). Regional lidocaine increased conduction velocity dispersion by 100% to 200% (P=0.01) but did not change ERP dispersion, whereas d-sotalol increased ERP dispersion by 140% (P<0.001) without affecting conduction velocity dispersion. Lidocaine infusion induced ventricular fibrillation (VF) in 6 of 7 animals, whereas regional d-sotalol was not proarrhythmic. Regional infusion of lidocaine and d-sotalol prolonged VF cycle length by 23% to 41% (P<0.05) in the perfused region and increased VF cycle length dispersion by 85% to 240% (P<0.05). Both agents increased pacing threshold (excitability) in the perfused region by 93% to 116% (P<0.05).


CONCLUSIONS
Regional conduction velocity slowing increased DER values, which was probably a result of spatial dispersion of conduction velocity. Increasing refractory period dispersion without changing conduction velocity did not alter DFT values. Thus, dispersion of conduction velocity may be a more likely regulator of defibrillation efficacy than dispersion of refractoriness.
Ujhelyi
M R
MR
University of Georgia College of Pharmacy, Augusta VA Medical Center, and Medical College of Georgia School of Medicine, Augusta, USA. michael.ujhelyi@medtronic.com
Sims
J J
JJ
Miller
A W
AW
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004553:Electric Conductivity; D004554:Electric Countershock; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D007473:Ion Channels / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology / Q000627:therapeutic use; D013015:Sotalol / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D008012:Lidocaine; D013015:Sotalol