J. Sprung et al., EFFECTS OF HYPOTHERMIA, POTASSIUM, AND VERAPAMIL ON THE ACTION-POTENTIAL CHARACTERISTICS OF CANINE CARDIAC PURKINJE-FIBERS, Anesthesiology, 82(3), 1995, pp. 713-722
Background: Hypothermia may induce hypokalemia and increase intracellu
lar Ca2+ by affecting serum K+ and Ca2+ fluxes across the cell membran
e. These ionic alterations may significantly change the electrophysiol
ogic characteristics of the cardiac action potential and may induce ca
rdiac arrhythmias. The current study was undertaken to determine wheth
er electrophysiologic changes in Purkinje fibers induced by hypothermi
a could be reversed by manipulating the extracellular K+ and transmemb
rane Ca2+ fluxes by Ca2+ channel blockade with verapamil. Methods: A c
onventional microelectrode method was used to determine the effects of
hypothermia (32 +/- 0.5 degrees C and 28 +/- 0.5 degrees C) various e
xternal K+ concentrations ([K+](o)) (2.3, 3.8, and 6.8 mM) on maximum
diastolic potential, maximum rate of phase 0 depolarization (V-max), a
nd action potential duration (APD) at 50% (APD(50)) and at 95% (APD(95
)) repolarization in isolated canine cardiac Purkinje fibers. To evalu
ate the contributional of the slow inward Ca2+ current to action poten
tial changes in hypothermia, the experiments were repeated in the pres
ence of the Ca2+-channel antagonist verapamil (1 mu M). Results: Varia
tions of [K+](o) induced the expected shifts in maximum diastolic pote
ntial, and hypothermia (28 degrees C) induced moderate depolarization,
but only when [K+](o) was greater than or equal to 3.9 mM (P < 0.05).
Hypothermia decreased V-max at all [K+](o) studied (P < 0.05). Regard
less of the temperature, V-max was not affected by verapamil when [K+]
(o) was less than or equal to 3.9 mM, but at 6.8 mM [K+](o) in hypothe
rmia V-max was significantly lower in the presence of verapamil. Hypot
hermia increased both the APD(50) and the APD(95). The effects of vera
pamil on APD were temperature and [K+](o) dependent; between 37 degree
s C and 28 degrees C with 2.3 mM [K+](o) in the superfusate, verapamil
did not affect APD. At 28 degrees C in the presence of verapamil, the
APD(50) and APD(95) decreased only if the [K+](o) was greater than or
equal to 3.3 mM. Conclusions: Verapamil and K+ supplementation in hyp
othermia may exert an antiarrhythmic effect, primarily by reducing the
dispersion of prolonged APD.