The effects of milrinone on action potential characteristics, conduction, automaticity, and reflected reentry in isolated myocardial fibers.
Milrinone, a newly developed analogue of amrinone, possesses potent positive inotropic effects. Electrophysiologic actions of the drug have thus far been reported in only one study conducted on canine Purkinje fibers. The present study used microelectrode techniques to evaluate the electrophysiologic effects of milrinone on normal and depressed isolated ventricular myocardial fibers. At apparent therapeutic concentrations (0.1-0.2 microgram/ml), milrinone abbreviated action potential duration and refractory period in normal myocardial fibers, but caused no significant changes in any other parameter. At similar concentrations, the drug markedly altered the electrical activity of K+-depolarized preparations, producing an increase in action potential amplitude, duration, and dV/dtmax. Milrinone also restored regenerative activity in K+-inactivated ventricular fibers. The drug exerted important effects on conduction velocity, refractoriness, and reflected reentry generated in fibers mounted in a three-compartment chamber in which the central segment was depressed with an "ischemic" solution. Depending on the initial level of block, the drug concentration, and the segments of the preparation exposed to the drug, milrinone (a) suppressed the arrhythmia, (b) shifted its frequency dependence, or (c) induced reentry. Similar results were obtained in homogeneously depressed fibers. The drug produced no major changes in depolarization-induced automaticity. Thus, in addition to its inotropic actions, milrinone produces important electrophysiologic effects. By restoring or improving conduction through areas of depressed conductivity, the drug may alter the manifestation of arrhythmias.
Davidenko
J
J
Antzelevitch
C
C
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002415:Cats; D003327:Coronary Disease / Q000503:physiopathology; D004285:Dogs; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D020105:Milrinone; D011188:Potassium / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology*
D002316:Cardiotonic Agents; D011728:Pyridones; D020105:Milrinone; D011188:Potassium