Na+-K+ pump inhibition caused by chronic amiodarone in guinea pig myocardium.
Although it is known that amiodarone inhibits myocardial Na+-K+ pump activity, the potency and the time course of this inhibition are unknown. The aim of this study was to investigate these aspects with reference to digoxin, using guinea pigs treated with either intraperitoneal amiodarone (20mg/kg per week, up to 12 weeks, n = 26) or the same amount of vehicle as a control (n = 24). ECG recording and microelectrode experiments were conducted every 2 weeks. QT interval corrected by heart rate and action potential duration were prolonged as a function of the time of exposure to amiodarone. Hyperpolarization observed immediately after the overdrive (1.0Hz) termination or K+-replenishment following K+-depletion in the presence of 0.1mM Ba2+ was compared in the amiodarone-treated and untreated groups, as an index of the Na+-K+ pump activity. The resting membrane potential recovery from overdrive-induced depolarization was slower and the amplitude of K+-induced hyperpolarization was smaller in the amiodarone-treated group than in the untreated group. These changes were evident as the chronic amiodarone treatment progressed, although the changes in these parameters were greater in the case of acute application of 50 microM digoxin. In conclusion, this study indicates that treatment with amiodarone for longer than several weeks moderately inhibits the myocardial Na+-K+ pump.
Maruyama
T
T
Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan.
Ueda
N
N
Kaji
Y
Y
Kanaya
S
S
Fujino
T
T
Niho
Y
Y
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004077:Digoxin / Q000008:administration & dosage; D004562:Electrocardiography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; D000638:Amiodarone