Faculty Collaboration Database

A comparison of three phosphodiesterase type III inhibitors on mechanical and metabolic function in guinea pig isolated hearts. Anesth Analg 2006 Jun;102(6):1646-52

Date

05/24/2006

Pubmed ID

16717301

DOI

10.1213/01.ane.0000216290.74626.27

Scopus ID

2-s2.0-33744462053 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

Little is known about of the comparative cardiac lusitropic and coronary vasoactive effects of type III phosphodiesterase inhibitors independent of their systemic circulatory effects. We hypothesized that phosphodiesterase inhibitors have dissimilar concentration-dependent effects on cardiac function and metabolism and that their coronary vasodilatory effects are solely dependent on flow autoregulation secondary to positive inotropic effects. Our aim was to compare the dose-response electrophysiologic, mechanical, vasodilatory, and metabolic properties of three clinically available phosphodiesterase inhibitors in isolated Langendorff perfused guinea pig hearts. We found that, over a range from 10(-7) to 10(-4) M, amrinone, enoximone, and milrinone each produced maximal concentration-dependent positive chronotropic (12%, 18%, 26%), inotropic (16%, 26%, 26%), and lusitropic (14%, 21%, 19%) effects. At clinical concentrations, all phosphodiesterase inhibitors increased heart rate, but only milrinone significantly enhanced contractility and relaxation (11%). Each phosphodiesterase inhibitor similarly increased contractility at its highest concentration; this was accompanied by an increase in oxygen consumption, which was matched by comparable increases in coronary flow and oxygen delivery. Coronary flow reserve was preserved at the highest concentration of each drug, indicating that an increased metabolic rate was responsible for the increase in coronary flow by each drug at each concentration. Over the concentrations examined, we conclude that each of the phosphodiesterase inhibitors does not directly promote coronary vasodilation and that milrinone has the most prominent effects on contractility and relaxation at clinically relevant concentrations.

Author List

Zausig YA, Stowe DF, Zink W, Grube C, Martin E, Graf BM

MESH terms used to index this publication - Major topics in bold

Amrinone
Animals
Cardiotonic Agents
Coronary Circulation
Dose-Response Relationship, Drug
Enoximone
Guinea Pigs
Heart
Heart Rate
In Vitro Techniques
Milrinone
Myocardial Contraction
Myocardium
Oxygen Consumption
Phosphodiesterase Inhibitors
Vasodilation