Effects of levosimendan versus dobutamine on pressure load-induced right ventricular failure.
OBJECTIVE
A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects of dobutamine and levosimendan on RV-PA coupling in this model of RV failure.


METHODS
Prospective, controlled, randomized animal study.


METHODS
University research laboratory.


METHODS
Fifteen anesthetized dogs.


METHODS
Transient (90-min) PA constriction to induce persistent RV failure. Random assignment to dobutamine 5 and 10 microg/kg/min or levosimendan 12 microg/kg for 10 mins followed by 0.1 and 0.2 microg/kg/min.


RESULTS
We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. PA constriction persistently increased PA resistance and elastance, increased Ea from 0.95 +/- 0.07 to 3.01 +/- 0.28 mm Hg/mL, decreased Ees from 1.17 +/- 0.09 to 0.58 +/- 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26 +/- 0.09 to 0.22 +/- 0.03 (p < .05). Dobutamine did not affect pulmonary hemodynamics, markedly increased RV contractility, and improved RV-PA coupling. Levosimendan decreased PA resistance and elastance, increased RV contractility, and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV afterload and therefore better restored RV-PA coupling at similar inotropic state.


CONCLUSIONS
A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan restores RV-PA coupling better than dobutamine because of similar inotropic effects and additional pulmonary vasodilatory effects.
Kerbaul
François
F
Laboratory of Physiology, Free University of Brussels, Brussels, Belgium.
Rondelet
Benoît
B
Demester
Jean-Paul
JP
Fesler
Pierre
P
Huez
Sandrine
S
Naeije
Robert
R
Brimioulle
Serge
S
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use*; D004285:Dogs; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006835:Hydrazones / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000150:complications*; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects; D011724:Pyridazines / Q000627:therapeutic use*; D011897:Random Allocation; D000077464:Simendan; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000209:etiology
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D004280:Dobutamine