Xl. Ren et Bf. Hoffman, REVERSIBILITY OF ELECTROPHYSIOLOGIC ABNORMALITIES OF SUBENDOCARDIAL PURKINJE-FIBERS INDUCED BY ISCHEMIA, Journal of cardiovascular electrophysiology, 5(5), 1994, pp. 412-421
Introduction: During the subacute phase of infarction in the canine he
art, the subendocardial Purkinje fibers subtended by the infarct show
depolarization greater than can be accounted for by the decrease in [K
+](i), and generate abnormal action potentials and spontaneous rhythms
due to abnormal automaticity. We have used pinacidil to hyperpolarize
these fibers and evaluate the extent to which an increase in resting
potential can normalize action potential generation. Methods and Resul
ts: Twenty-four hours after two-stage ligation of the canine left ante
rior descending coronary artery, preparations of subendocardial Purkin
je fibers were studied in vitro by recording transmembrane potentials
through standard microelectrodes and exposing the preparation to pinac
idil and increases in [K+](o). Pinacidil increased resting potential t
o the estimated value of E(K), abolished the abnormal automaticity, an
d restored action potentials of normal amplitude with normal values of
V-max. This effect often persisted after washout of pinacidil. Elevat
ion of [K+](o) from 4.0 to 20.0 mM slightly increased maximum diastoli
c potential, suggesting that the excess (over the change in E(K)) depo
larization was caused by a decrease in g(K1). Conclusion: The ventricu
lar arrhythmias seen during the subacute stage of infarction probably
are caused by abnormal automaticity. Our findings support the conclusi
on that this abnormal automaticity arises in partially depolarized sub
endocardial Purkinje fibers. This loss of resting potential is due in
large part to a decrease in g(K1). Restoration of resting potential to
the value of E(K) permits the Purkinje fibers to develop essentially
normal action potentials. An agent capable of reversing the partial bl
ock of I-K,I-1 thus might be an effective drug for some types of arrhy
thmias.