Gap junction blockers decrease defibrillation thresholds without changes in ventricular refractoriness in isolated rabbit hearts.
BACKGROUND
The maintenance and termination of reentry arrhythmias are determined by tissue properties such as refractoriness and conduction velocity. Although the effects of Na(+) and K(+) channel block on electrophysiological properties and defibrillation threshold (DFT) have been studied, little is known about the effect of gap junction blockers on defibrillation and tissue electrophysiological properties.


RESULTS
Triplicate DFTs (volts) were obtained before and 15 minutes after 4 micromol/L 16-doxyl-stearic acid (16-DSA, n=8), 1 mmol/L 1-heptanol (n=12) (both gap junction blockers), 3 microg/mL lidocaine (a sodium channel blocker) (n=8), and respective controls (n=27) in isolated perfused rabbit hearts. DFT decreased after 16-DSA (23+/-14%, P<0.01) and 1-heptanol (21+/-16%, P<0.01) but increased after lidocaine (26+/-28%, P<0.05). Ventricular fibrillation cycle length (VFCL) and QRS duration increased after all 3 agents, by 36+/-19% and 44+/-16% (16-DSA), 87+/-42% and 49+/-15% (heptanol), and 57+/-20% and 43+/-26% (lidocaine), respectively (all P<0.01). Spatially averaged temporal VFCL dispersion decreased significantly after all 3 agents, by 47+/-42% (16-DSA, P<0.05), 74+/-19% (1-heptanol, P<0.01), and 82+/-13% (lidocaine, P<0.01), respectively. Ventricular effective refractory period and monophasic action potential duration at 90% repolarization were unchanged after 16-DSA and 1-heptanol (P=NS) but increased after lidocaine (16+/-13%, P<0.01, and 6+/-5%, P=NS, respectively). There were no significant changes in DFT or any other electrophysiological variable in control hearts.


CONCLUSIONS
Electrical uncoupling by 16-DSA and 1-heptanol significantly lowers DFT and dispersion of VFCL without altering refractoriness; lidocaine, at doses resulting in similar slowing of conduction, increases DFT.
Qi
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Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ont, Canada.
Varma
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P
Newman
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Dorian
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P
D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004554:Electric Countershock; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D019850:Heptanol / Q000494:pharmacology*; D008297:Male; D011817:Rabbits
D003497:Cyclic N-Oxides; C032363:16-nitroxystearic acid; D019850:Heptanol