Effect of milrinone on ethanol and halothane induced cardiodepression.
The inotropic effect of milrinone was studied in isolated rat and cat heart preparations. In the spontaneously beating isolated rat atria a dose-related initial positive inotropic effect was observed, reaching the highest percent increase in tension developed (TD) of +26.5 +/- 2.8% with the dose of 25 micrograms/ml milrinone and a maximal increase in spontaneous rate of +60.2 +/- 6% with the dose of 80 micrograms/ml. However, in electrically driven rat atria, the maximal increase in TD was +39.2 +/- 3.4%. The difference of both preparations might be due to the negative staircase in rat limiting increase in TD in spontaneously beating atria. In electrically driven isolated cat atria the positive inotropic effect of milrinone appeared with 0.5 micrograms/ml and the maximal effect (36% increase in TD) with the dose of 8 micrograms/ml. In cat papillary muscle the dose-response relationship appeared upward and to the left as compared to rat atrial preparations and reached a maximal TD increase of around 90%. Ethanol (22 and 44 mM) induced a dose-related significant decrease of TD in isolated rat atrial preparations, that was reversed by milrinone, and its dose-effect relationship was similar in the presence as well as in ethanol-free medium. In the isolated cat heart papillary muscle, ethanol 44 mM decreased TD 15.1 +/- 1.8%. Milrinone in concentrations up to 8 micrograms/ml increased TD in a significantly lower magnitude than in ethanol-free medium. However, with higher milrinone concentrations (16-120 micrograms/ml) no difference was observed between both conditions. In spontaneously beating right atria halothane 20 micrograms/ml induced a negative inotropic effect revealed by a 33.8 +/- 4.2% decrease in TD, which was reversed by milrinone in a dose-dependent manner. This relative percent increase in TD was significantly greater in halothane exposed atria than in halothane-free experiments. Phosphodiesterase blockade increasing cyclic AMP, which appears to be the main mechanism for the inotropic effect of milrinone, might participate in the reversal of the cardiodepression by both ethanol and halothane or eventually by modifying directly calcium availability.
Neira
S
S
Departamento de Farmacología, Facultad de Medicina, Universidad de Chile, Santiago.
Penna
M
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002415:Cats; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D006221:Halothane / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats
D002316:Cardiotonic Agents; D011728:Pyridones; D000431:Ethanol; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D020105:Milrinone; D006221:Halothane