Acute effects of amiodarone on ultrastructure and electrical activity of isolated guinea pig hearts.

STUDY OBJECTIVE--The aim was to evaluate the effects of tissue concentration of amiodarone on ultrastructure and electrical activity in isolated spontaneously beating Langendorff perfused guinea pig hearts. DESIGN--Group 1: The influence of 10 microM amiodarone over a period of 1 h in a non-recirculated perfusate on conduction intervals, heart rate, creatine kinase concentration in the coronary effluent, coronary flow, and drug accumulation was determined. Group 2: Ultrastructural changes after 30 min and 60 min perfusion with amiodarone were examined. Group 3: Cardiac refractoriness was evaluated following 30 min and 60 min of perfusion with amiodarone. EXPERIMENTAL PREPARATIONS--Isolated hearts of guinea pigs (200-300 g) were used: group 1, n = 6 animals; group 2, n = 3 for each time span; and group 3, n = 6 for each time span. MEASUREMENTS AND MAIN RESULTS--A steady state for the effects of amiodarone on atrioventricular and intraventricular conduction [+31(SEM 5)%, p less than 0.01% +47(12)%, p less than 0.01, respectively] and on heart rate [-30(9)%, p less than 0.01] was reached after 15 min, and on His bundle conduction [+38(17)%, p less than 0.01] after 30 min. QT duration was not affected throughout the duration of the experiment. Cardiac refractoriness was significantly prolonged following 30 min perfusion with 10 microM amiodarone, and was further significantly increased following 60 min perfusion. Amiodarone tissue concentration increased to 365(39) nmol.g-1 wet weight, and this was accompanied by an increase in creatine kinase concentration in the coronary effluent. Coronary flow stayed constant throughout the whole experiment. At the end of the experiment electron microscopic examination of the myocardium of the left ventricle showed accumulation, fusion, and vacuolisation of mitochondria, and perinuclear oedema. CONCLUSIONS--These observations suggest that amiodarone, as well as exerting acute electrophysiological effects, creates ultrastructural changes which probably contribute to its effectiveness in arrhythmias caused by scarred myocardium.