Intravenous Amiodarone and Sotalol Impair Contractility and Cardiac Output, but Procainamide Does Not: A Langendorff Study

Abstract

Introduction.-Direct comparison of the effects of antiarrhythmic agents on myocardial performance may be useful in choosing between medications in critically ill patients. Studies directly comparing multiple antiarrhythmic medications are lacking. The use of an experimental heart preparation permits examination of myocardial performance under constant loading conditions. Methods.-Hearts of Sprague Dawley rats (n=35, 402-507 grams) were explanted and cannulated in working heart mode with fixed preload and afterload. Each heart was then exposed to a 3-hour infusion of either procainamide (20 μg/kg/min), esmolol (100 or 200 μg/kg/min), amiodarone (10 or 20 mg/kg/day), sotalol (80 mg/m2/day), or placebo infusions (n=5 per dose). Cardiac output (CO), contractility (dP/dTmax), diastolic performance (dP/dTmin), and heart rate were compared between groups over time by linear mixed modeling. Results.-Compared with placebo, sotalol decreased contractility by an average of 24% (P<0.001) over the infusion period, as did amiodarone (low dose by 13%, P=0.029; high dose by 14%, P=0.013). Compared with placebo, mean cardiac output was significantly lower in animals treated with sotalol (by 22%, P=0.016) and esmolol 200 mcg/kg/min (by 23%, P=0.012). Over time, amiodarone decreased cardiac output (20 mg/kg/day, β=−89 [−144, −33] μL/min2 decrease, P = 0.002) and also worsened diastolic function, decreasing dP/dTmin by ~18% and 22% (P=0.032 and P=0.011, low and high doses). Procainamide did not have a significant effect on any measures of systolic or diastolic performance. Conclusions.-In isolated hearts, amiodarone and sotalol depressed myocardial contractility, cardiac output, and diastolic function. However, procainamide did not negatively affect myocardial performance, and represents a favorable agent in settings of therapeutic equivalence.

Effects of Amiodarone and Esmolol for Heart Rate and Cardiovascular Changes

“…The data show that the incidence population tends to be young, in which unhealthy lifestyle is the main induced factor [ 11 ]. At present, the use of amiodarone treatment can be improved on the symptoms of paroxysmal tachycardia, and it is also suitable for myocardial infarction treatment [ 12 ].…”

The Interaction of Amiodarone and Continuous-flow Left Ventricular Assist Device Use in Risk of Severe Primary Graft Dysfunction Following Heart Transplantation

“…In several animal model studies, amiodarone reduced myocardial contractility and cardiac output and worsen diastolic function that is suggestive of a negative inotropic and lusitropic effect. 14,15 Although the negative inotropic effect was previously demonstrated in human studies involving intravenous amiodarone loading, it has not been observed with chronic oral amiodarone consumption. [16][17][18] In contrast, a study by See et al postulated an immunologic response in recipients of prior ventricular assist device as a mechanism for PGD following heart transplantation.…”

A Retrospective Cohort Evaluation of Left Ventricular Remodeling, Perioperative Complications and Outcome in Medium and Large Size Dogs with Patent Ductus Arteriosus after Percutaneous Closure

“…In human medicine, the effect of amiodarone on heart contractility is debated. In some studies there is an improvement in systolic function or cardiac output, while in others the intravenous administration of this drug depresses myocardial contractility in isolated hearts [ 41 , 42 , 43 ].…”