Reentrant circuits and the effects of heptanol in a rabbit model of infarction with a uniform anisotropic epicardial border zone.
BACKGROUND
The purpose was to study reentry in a rabbit model of infarction.


RESULTS
A model of an infarct epicardial border zone was produced in Langendorff perfused rabbit hearts by freezing the inner two thirds of the left ventricular wall, allowing only a thin epicardial muscle layer to survive. Reentrant circuits causing stable ventricular tachycardia occurred in the surviving rim of epicardial muscle as shown by mapping impulse propagation with a 196-electrode array. The circuits were functional, and reentry did not occur around an anatomical obstacle. Slow conduction in the circuits was caused by the anisotropic properties of the epicardial muscle. Activation in the circuits was slow transverse to the long axis of the fiber bundles and rapid parallel to the long axis. Other features of the circuits, including orientation of the central functional line of block parallel to the fiber long axis, and an oval shape are also characteristic of anisotropic reentry. Since the slow conduction causing reentry is a result of poor transverse intercellular coupling, we determined whether the "uncoupler" heptanol would cause block in the circuits and terminate tachycardia. Heptanol in concentrations up to 1.2 mM slowed conduction in the transverse and longitudinal directions in the circuits and sometimes extended the central line of functional block. It did not, however, stop reentry because the reentrant impulse was still able to conduct around the ends of the block line.


CONCLUSIONS
Drugs that decrease intercellular coupling may not be effective antiarrhythmic agents when uniform anisotropy causes functional reentry.
Nassif
G
G
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Dillon
S M
SM
Rayhill
S
S
Wit
A L
AL
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D016880:Anisotropy; D004195:Disease Models, Animal; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006352:Heart Ventricles; D019850:Heptanol; D009203:Myocardial Infarction / Q000503:physiopathology*; D011817:Rabbits; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology
D000438:Alcohols; D019850:Heptanol