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(Circulation. 1999;99:1623-1629.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Effects of Ischemia on Discontinuous Action Potential Conduction in Hybrid Pairs of Ventricular Cells

Ronald Wilders, PhD; E. Etienne Verheijck, PhD; Ronald W. Joyner, MD, PhD; David A. Golod, MSc; Rajiv Kumar, PhD; Antoni C. G. van Ginneken, PhD; Lennart N. Bouman, MD; Habo J. Jongsma, PhD

From the Department of Medical Physiology and Sports Medicine, Utrecht University (R.W., E.E.V., H.J.J.), and the Academic Medical Center, University of Amsterdam, Department of Physiology, Amsterdam (R.W., E.E.V., A.C.G.v.G., L.N.B.), Netherlands; and Todd Franklin Cardiac Research Laboratory, The Children's Heart Center, Department of Pediatrics, Emory University, Atlanta, Ga (R.W.J., D.A.G., R.K.).

Correspondence to Ronald Wilders, Department of Medical Physiology and Sports Medicine, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, PO Box 80043, 3508 TA Utrecht, Netherlands. E-mail r.wilders{at}med.uu.nl

Background—Acute ischemia often occurs in cardiac tissue that has prior injury, resulting in spatially inhomogeneous distributions of membrane properties and intercellular coupling. Changes in action potential conduction with ischemia, which can be associated with release of catecholamines, may be particularly important in tissue that has discontinuous conduction resulting from prior infarction, hypertrophy, or myopathy.

Methods and Results—Isolated guinea pig ventricular myocytes were electrically coupled by a coupling-clamp circuit to a comprehensive computer model of a guinea pig ventricular myocyte to assess alterations in the critical value of coupling conductance required for action potential conduction from the real cell to the model cell when the real cell was exposed to a solution that included hypoxia, acidosis, and an elevated extracellular potassium concentration to simulate acute ischemia. The "ischemic" solution increased critical coupling conductance from 6.2±0.1 to 7.4±0.2 nS and decreased the associated maximum conduction delay from 31±1 to 23±1 ms (mean±SEM, n=11). The ischemic solution plus 1 µmol/L norepinephrine decreased critical coupling conductance from 5.9±0.2 to 5.0±0.1 nS and increased maximum conduction delay from 31±2 to 54±4 ms (mean±SEM, n=8).

Conclusions—The release of catecholamines with ischemia, in a setting of partially uncoupled cells, may play a major role in producing long conduction delays, which may allow reentrant pathways.

Key Words: arrhythmia • catecholamines • conduction • ischemia

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