Effects of amiodarone with and without polysorbate 80 on myocardial oxygen consumption and coronary blood flow during treadmill exercise in the dog.
Since amiodarone has been reported to possess antianginal activity, this study examined the effects of amiodarone on coronary blood flow and myocardial oxygen consumption during exercise. Studies were performed in 14 chronically instrumented dogs trained to run on a motor-driven treadmill. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter while aortic and coronary sinus catheters allowed measurement of myocardial oxygen extraction. During control conditions, graded exercise resulted in progressive increases in heart rate, aortic pressure, and coronary blood flow. Two preparations of amiodarone, 5 mg/kg, one dissolved in sterile water and the other in 10% polysorbate 80, were given intravenously to separate groups of dogs. Amiodarone in sterile water caused no hemodynamic changes at rest. However, the increase in heart rate during exercise was blunted after amiodarone, so that heart rate during the heaviest level of exercise was significantly less than during control exercise. Coronary blood flow and myocardial oxygen consumption were unchanged. Amiodarone with polysorbate 80 also blunted the increase in heart rate during exercise, but in addition caused a significant decrease in aortic pressure both at rest and during exercise. Myocardial oxygen consumption and coronary blood flow were significantly decreased after administration of amiodarone with polysorbate 80 at rest and during all exercise levels. Amiodarone with or without polysorbate 80 did not change myocardial oxygen extraction. These data demonstrate that amiodarone exerts a negative chronotropic effect during exercise. However, the decreased arterial pressure and myocardial oxygen consumption were not due to amiodarone, but was seen only with the combination of amiodarone dissolved in polysorbate 80.
Path
G J
GJ
Department of Medicine, University of Minnesota Medical School, Minneapolis.
Dai
X Z
XZ
Schwartz
J S
JS
Benditt
D G
DG
Bache
R J
RJ
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010805:Physical Conditioning, Animal; D011136:Polysorbates / Q000494:pharmacology*
D011136:Polysorbates; D000638:Amiodarone