September 1, 1991Open Access
View Full PaperDifferential effects of heptanol, potassium, and tetrodotoxin on reentrant ventricular tachycardia around a fixed obstacle in anisotropic myocardium.
Key Result
In a rabbit heart model of reentrant VT, heptanol preferentially depressed transverse conduction, whereas high potassium and tetrodotoxin preferentially slowed longitudinal conduction.
Structured PICO
Do heptanol, potassium, and tetrodotoxin have differential effects on the propagation of electrical impulses relative to fiber orientation during reentrant ventricular tachycardia?
P
Population
Langendorff-perfused rabbit hearts with a model of reentrant ventricular tachycardia (VT) around a ring of anisotropic myocardium (n=16 total; 10 for heptanol/potassium, 6 for tetrodotoxin)
I
Intervention
Heptanol, high extracellular potassium ([K+]o), and tetrodotoxin
C
Comparator
Baseline state (dose-dependent effects evaluated)
O
Outcome
VT cycle length, longitudinal and transverse conduction velocities, and mechanism of VT terminationsurrogate
Electrical uncoupling by heptanol and depression of fast sodium channels by high potassium or tetrodotoxin exert differential, orientation-dependent depressing effects on impulse propagation during reentrant ventricular tachycardia.
Abstract
BACKGROUND: The aim of this study was to test the hypothesis that electrical uncoupling and depression of the fast sodium channels have differential effects on propagation of the electrical impulse relative to the fiber orientation. METHODS AND RESULTS: In a model of reentrant ventricular tachycardia (VT) (mean cycle length, 144 +/- 13 msec) around a ring of anisotropic myocardium in 10 Langendorff-perfused rabbit hearts, the effects of extracellular K+ concentration ( K+o) and heptanol were studied. K+o and heptanol each had a dose-dependent effect on VT cycle length. However, high K+o slowed the VT mainly by depressing longitudinal conduction, whereas heptanol preferentially depressed transverse conduction. The ratio between longitudinal and transverse conduction velocities progressively decreased with high K+o and progressively increased with heptanol. Heptanol terminated VT at a mean concentration of 3.5 +/- 0.5 mM. The cycle length before termination was 446 +/- 120 msec (p less than 0.001). In eight of 10 experiments, termination occurred by failure of conduction during transverse propagation. VT terminated at a mean K+o of 11.6 +/- 1.8 mM. The cycle length before termination was 493 +/- 341 msec (p less than 0.01). In seven of 10 cases, termination occurred by failure of conduction during longitudinal propagation. In the remaining five episodes (two with heptanol and three with high K+o), termination occurred by collision of the reentrant beat with an antidromic impulse being reflected within the ring. In a separate series of six hearts, tetrodotoxin was administered during VT. Like high K+o, tetrodotoxin prolonged the cycle length of the VT by preferentially slowing longitudinal conduction, and VT was terminated by longitudinal block. CONCLUSIONS: During reentrant VT, electrical uncoupling of cells by heptanol or modification of active membrane properties by high K+o or tetrodotoxin has a differential depressing effect on propagation of the impulse relative to the fiber orientation.