Local epicardial inotropic drug delivery allows targeted pharmacologic intervention with preservation of myocardial loading conditions

Local myocardial application of inotropes may allow the study of pharmacologically augmented central myocardial contraction in the absence of confounding peripheral vasodilating effects and alterations in heart loading conditions. Novel alginate epicardial (EC) drug releasing platforms were used to deliver dobutamine to the left ventricle of rats. Pressure-volume analyses indicated that although both local and systemic intravenous (i.v.) use of inotropic drugs increase stroke volume and contractility, systemic infusion does so through heart unloading. Conversely, EC application preserves heart load and systemic blood pressure. EC dobutamine increased indices of contractility with minimal rise in heart rate and lower reduction in systemic vascular resistance than i.v. infusion. Drug sampling showed that dobutamine concentration was 650‐fold higher in the anterior wall than in the inferior wall. The plasma dobutamine concentration with local delivery was about half as much as with systemic infusion. These data suggest that inotropic EC delivery has a localized effect and augments myocardial contraction by different mechanisms than systemic infusion, with far fewer side effects. These studies demonstrate a pharmacologic paradigm that may improve heart function without interference from effects on the vasculature, alterations in heart loading, and may ultimately improve the health of heart failure patients. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4993-5006, 2011