Direct cardiac effects of dobutamine, dopamine, epinephrine, and levosimendan in isolated septic rat hearts.
In septic patients, myocardial depression-the so-called septic cardiomyopathy-needing inotropic support is common. The aim of this study was to compare the dose-responsive electrophysiological and mechanical properties concerning metabolic effects of clinically available inotropic agents in an isolated septic rat heart model. After 20 h of incubation, both sham-operated and septic (cecal ligation and single puncture) hearts from male Wistar rats (n = 64) were isolated and received dobutamine, dopamine, epinephrine, or levosimendan at concentrations of 10 to 10 M. Electrophysiological, mechanical, and metabolic properties were measured, and the myocardial oxygen supply-demand ratio and cardiac efficiency were calculated. With the exception of levosimendan, all of the drugs tested showed dose-dependent, significantly positive changes in chronotropy, inotropy, and lusitropy in all hearts. Maximum increases in septic hearts were dose-dependent and were ordered as follows: epinephrine > dopamine > dobutamine >>> levosimendan. These increases in cardiac performance were accompanied by a decrease in the myocardial oxygen supply-demand ratio. However, cardiac efficiency was significantly improved in the epinephrine-treated septic hearts. With the drug-induced increase in cardiac performance, the myocardial oxygen supply-demand ratio decreased proportionally in the epinephrine-, dobutamine-, and dopamine-treated septic hearts. However, epinephrine showed the most favorable results with regard to cardiac efficiency, and levosimendan showed no beneficial effect in septic hearts with regard to efficiency in this study.
Zausig
York A
YA
Department of Anaesthesiology, University of Regensburg, Regensburg, Germany. york.zausig@klinik.uni-regensburg.de
Geilfus
Diana
D
Missler
Goetz
G
Sinner
Barbara
B
Graf
Bernhard M
BM
Zink
Wolfgang
W
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010538:Peritonitis / Q000150:complications; D011724:Pyridazines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D000077464:Simendan; D013810:Therapeutic Equivalency
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D004280:Dobutamine; D004298:Dopamine; D004837:Epinephrine