Oxygen-wasting effect of inotropy: is there a need for a new evaluation? An experimental large-animal study using dobutamine and levosimendan.
BACKGROUND
We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient.


RESULTS
Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 microg/kg loading and 0.04 microg x kg(-1) x min(-1) infusion) or an equipotent dose of dobutamine (1.25 microg x kg(-1) x min(-1)). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 microg x kg(-1) x min(-1) and 48 microg/kg loading with 0.2 microg x kg(-1) x min(-1) infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area).


CONCLUSIONS
Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.
Müller
Stig
S
Department of Cardiothoracic and Vascular Surgery, University Hospital North Norway, and Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
How
Ole-Jakob
OJ
Jakobsen
Øyvind
Ø
Hermansen
Stig Eggen
SE
Røsner
Assami
A
Stenberg
Thor Allan
TA
Myrmel
Truls
T
D000704:Analysis of Variance; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology*; D006835:Hydrazones / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017682:Myocardial Stunning / Q000188:drug therapy*; D010101:Oxygen Consumption / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D013552:Swine
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D004280:Dobutamine