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Am J Physiol Heart Circ Physiol (March 6, 2003). doi:10.1152/ajpheart.01074.2002
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Submitted on December 10, 2002
Accepted on February 26, 2003

Regional Gap Junction Inhibition Increases Defibrillation Thresholds

J. J Sims1*, Kell L Schoff1, Jennifer M Loeb1, and Nicholas A Wiegert1

1 School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA

* To whom correspondence should be addressed. E-mail: jjsims{at}pharmacy.wisc.edu.

It is clear that ischemia inhibits successful defibrillation by altering regional electrophysiology. However, the exact mechanisms are unclear. This study investigated if regional gap junction inhibition increases biphasic shock defibrillation thresholds (DFT). Sixteen swine were instrumented with a mid-LAD perfusion catheter for regional infusion of heptanol 0.5 mM/hour (n=8) or saline (n=8). Defibrillation threshold (DFT) values and effective refractory periods (ERP) at five myocardial sites were determined. Regional conduction velocity (CV) was determined in an LAD drug-perfused and non-drug perfused region in an additional seven swine. Regional heptanol infusion increased DFT50 values by 33% (p=0.01) slowed CV by 42-59% (p<0.01), but did not affect ERP. Regional heptanol also increased CV dispersion by approximately 270% (p<0.05), but did not change ERP dispersion. Regional placebo did not alter any of these parameters. Furthermore, regional heptanol infusion induced spontaneous ventricular fibrillation (VF) in 8/8 animals. Increasing spatial conduction velocity dispersion by impairing regional gap junction conductance increased DFT values. Dispersion in conduction velocity slowing during regional ischemia may be an important determinant of defibrillation efficacy.




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