Efficacy of dobutamine in the failing transplanted heart.
Acute rejection often leads to severe myocardial failure and death. Surprisingly, no systematic study on the efficacy of beta-adrenergic pharmacologic agents have been reported to the present. Because of all the pathophysiologic alterations documented during rejection, we expected an inappropriate response to inotropic drugs, so we have questioned the value of dobutamine during those circumstances. Twelve dogs underwent orthotopic transplantation and were prepared with implantable devices for serial hemodynamic studies to be performed on the resting unanesthetized subject. Of this number, six dogs were studied while they were in immediate postoperative heart failure (3 hours after operation), and the same study was performed when myocardial failure secondary to rejection occurred (5 to 7 days). After basal state measurement, 5 and 10 micrograms.kg-1.min-1 of dobutamine were infused continuously, and the hemodynamic response during the two phases was compared. The baseline cardiac index in the immediate postoperative period was 1.4 +/- 0.4 L.min-1.m2 and 1.8 +/- 1.0 L.min-1.m2 during rejection, showing a similar degree of heart failure. Dobutamine (5 micrograms.kg-1.min-1) increased cardiac index by 97% 3 hours after transplantation and by 35% during rejection (p < 0.05). With 10 micrograms.kg-1.min-1 of dobutamine, the difference between increments was not significant (99% versus 79%). Raising the infusion rate of the drug to 15 and 20 micrograms.kg-1.min-1 during rejection increased cardiac index by 97% and 118%, respectively. Interestingly, no detrimental tachycardia occurred with this increased dosage. Heart failure secondary to acute rejection can therefore be improved by dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS)
De Broux
E
E
Hôpital Ste-Justine, Département de pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Lagacé
G
G
Dumont
L
L
Chartrand
C
C
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004280:Dobutamine / Q000627:therapeutic use*; D004285:Dogs; D006084:Graft Rejection / Q000150:complications* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects
D004280:Dobutamine