Two weeks of intermittent dobutamine therapy restores cardiac performance and inotropic responsiveness in conscious rats with heart failure.
Dobutamine is frequently used for acute therapy in heart failure. In the present study, the hemodynamic effects of long-term intermittent dobutamine therapy were investigated in conscious rats with heart failure. Rats with healed myocardial infarctions received two i.p. injections of dobutamine per day for 2 weeks. Hemodynamic measurements were performed 90-180 min after the last injection. Two weeks of intermittent dobutamine significantly restored all hemodynamic changes induced by infarction. The maximal cardiac output during volume loading was depressed due to infarction and dose-dependently restored by 2 weeks of intermittent dobutamine. An increased stroke volume accounted for this improvement since the heart rate was not altered. In order to investigate changes in adrenergic responsiveness, the effects of acute dobutamine in nontreated and 2 weeks of dobutamine-treated infarcted rats were compared to those in control rats. Whereas chronotropic responses to acute dobutamine were comparable for all experimental groups, the inotropic response was reduced in nontreated infarcted rats but dose-dependently restored after 2 weeks of intermittent dobutamine therapy. From the data, we conclude that 2 weeks of intermittent dobutamine therapy in conscious rats with healed myocardial infarcts improved cardiac performance and restored the inotropic response to acute dobutamine administration. Data indicate that dobutamine has a long-term effect on cardiac function, which differs from the acute inotropic effect.
Schoemaker
R G
RG
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Debets
J J
JJ
Struyker-Boudier
H A
HA
Smits
J F
JF
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology; D004280:Dobutamine / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains
D004280:Dobutamine