Regional gap junction inhibition increases defibrillation thresholds.
It is clear that ischemia inhibits successful defibrillation by altering regional electro-physiology. However, the exact mechanisms are unclear. This study investigated whether regional gap junction inhibition increases biphasic shock defibrillation thresholds (DFT). Sixteen swine were instrumented with a mid-left anterior descending (LAD) perfusion catheter for regional infusion of 0.5 mM/h heptanol (n = 8) or saline (n = 8). 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 nondrug-perfused region in an additional seven swine. Regional heptanol infusion increased 50% DFT values by 33% (P = 0.01) and 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 in eight of eight 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.
Sims
J Jason
JJ
School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA. jjsims@pharmacy.wisc.edu
Schoff
Kell L
KL
Loeb
Jennifer M
JM
Wiegert
Nicholas A
NA
D000818:Animals; D002304:Cardiac Pacing, Artificial; D017630:Connexins / Q000502:physiology; D004554:Electric Countershock; D004562:Electrocardiography; D004594:Electrophysiology; D017629:Gap Junctions / Q000187:drug effects*; D019850:Heptanol / Q000494:pharmacology; D007700:Kinetics; D017202:Myocardial Ischemia / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D012032:Refractory Period, Electrophysiological / Q000502:physiology; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology* / Q000628:therapy; D016277:Ventricular Function, Left / Q000502:physiology
D017630:Connexins; D019850:Heptanol