ABSTRACT
Patients with severe congestive heart failure (CHF) are at increased risk for atrial and ventricular arrhythmias and sudden cardiac death. Amiodarone is generally well tolerated by this population and has a low proarrhythmic potential. Because of its peculiar kinetics, amiodarone requires a prolonged loading period, necessitating lengthy hospitalizations in a monitored setting. This study was planned prospectively to assess the electrophysiologic effects of an abbreviated high-dose oral load of amiodarone in patients with severe CHF and known or suspected life-threatening ventricular arrhythmias. Fifteen patients with stable CHF and known or suspected life-threatening ventricular arrhythmias underwent baseline electrophysiologic study. The study was repeated after administration of oral amiodarone, 50 mg/kg/day for 2 days in 8 divided doses (mean dose 6.9 +/- 0.4 g). After amiodarone administration, there was prolongation in virtually all conduction times and refractory periods. The prolongation of refractoriness was most pronounced in the atrium. Ventricular effective refractory periods demonstrated reverse frequency dependence. We conclude that a brief high-dose oral load of amiodarone is well tolerated by patients with CHF. It has marked and diffuse electrophysiologic actions suggestive of class I and III effects in addition to antiadrenergic and calcium blocking action. These effects are especially pronounced in the atrium.
Subject(s)
Amiodarone/therapeutic use , Heart Failure/physiopathology , Administration, Oral , Aged , Amiodarone/administration & dosage , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/etiology , Atrial Function/drug effects , Electrocardiography , Electrophysiology , Female , Heart/drug effects , Heart/physiopathology , Heart Failure/complications , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
OBJECTIVES: The purpose of this study was to use invasive monitoring to analyze the hemodynamic effects of both a large single dose and a 48-h loading regimen of amiodarone in patients with severe heart failure. BACKGROUND: Amiodarone is frequently used as an antiarrhythmic agent in patients with congestive heart failure, but the impact of this agent on cardiac function remains controversial. Recent successful experience with a rapid oral load of amiodarone makes invasive testing of the hemodynamic effects of oral amiodarone in such patients now feasible. METHODS: After baseline hemodynamic assessment (using balloon-tipped pulmonary artery catheters) and electrocardiographic measurements, 16 patients received 12.5 mg/kg body weight of amiodarone orally. Hemodynamic measurements were obtained hourly for 4 h. Patients then received this dose an additional seven times over the next 2 days. Hemodynamic variables and QRS, QT and PR intervals were measured after 48 h of treatment. RESULTS: Vasodilation was seen between 1 and 3 h after drug administration. Systemic vascular resistance decreased 326 +/- 135 dynes.s.cm-5, cardiac index increased 0.24 +/- 0.08 liters/min per m2 and mean arterial pressure decreased 6 +/- 3 mm Hg (mean +/- SEM, all p < 0.05). After 48 h of amiodarone administration, heart rate decreased 23 +/- 3 beats/min (p < 0.005), stroke volume increased 9 +/- 3 ml (p < 0.005), cardiac index decreased 0.23 +/- 0.09 ml/min per m2 (p < 0.05), pulmonary capillary wedge pressure increased 4 +/- 1 mm Hg (p < 0.01), right atrial pressure increased 3 +/- 1 mm Hg (p < 0.005) and QT and PR intervals were markedly prolonged (p < 0.01). CONCLUSIONS: Although the first dose caused vasodilation, a complete loading regimen of amiodarone produced a decreased heart rate with elevated filling pressures and decreased cardiac index.
Subject(s)
Amiodarone/pharmacology , Heart Failure/physiopathology , Hemodynamics/drug effects , Administration, Oral , Aged , Amiodarone/administration & dosage , Catheterization, Swan-Ganz , Dose-Response Relationship, Drug , Electrocardiography , Female , Humans , Male , Pulmonary Wedge Pressure/drug effects , Thermodilution , Time FactorsABSTRACT
In the pathogenesis of mycotic infections, adherence of the microbes to surface structures prior to invasion appears to be the initial and essential step in a susceptible host. Adherence and inhibition of adherence of Candida albicans to rabbit corneal surface was investigated in vitro by light and scanning electron microscopic examinations. The results indicate that blastospores of Candida albicans rarely bind to intact corneal epithelium, but consistently adhere to stroma denuded of epithelium. Such adherence was inhibited by concanavalin A. With its strong affinity for the yeast cell wall carbohydrate mannan, concanavalin A may block the site of attachment of yeast cells to the corneal surface.
