Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study.
OBJECTIVE
To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO(2)) and prevents intramucosal acidosis in septic shock.


METHODS
Prospective, controlled experimental study.


METHODS
University-based research laboratory.


METHODS
Nineteen anesthetized, mechanically ventilated sheep.


METHODS
Endotoxin-treated sheep were randomly assigned to three groups: control (n=7), dobutamine (10 microg/kg/min, n=6) and levosimendan (100 microg/kg over 10 min followed by 100 microg/kg/h, n=6) and treated for 120 min.


RESULTS
After endotoxin administration, systemic and intestinal DO(2) decreased (24.6+/-5.2 vs 15.3+/-3.4 ml/kg/min and 105.0+/-28.1 vs 55.8+/-25.9 ml/kg/min, respectively; p<0.05 for both). Arterial lactate and the intramucosal-arterial PCO(2) difference (DeltaPCO(2)) increased (1.4+/-0.3 vs 3.1+/-1.5 mmHg and 9+/-6 vs 23+/-6 mmHg mmol/l, respectively; p<0.05). Systemic DO(2) was preserved in the dobutamine-treated group (22.3+/-4.7 vs 26.8+/-7.0 ml/min/kg, p=NS) but intestinal DO(2) decreased (98.9+/-0.2 vs 68.0+/-22.9 ml/min/kg, p<0.05) and DeltaPCO(2) increased (12+/-5 vs 25+/-11 mmHg, p<0.05). The administration of levosimendan prevented declines in systemic and intestinal DO(2) (25.1+/-3.0 vs 24.0+/-6.3 ml/min/kg and 111.1+/-18.0 vs 98.2+/-23.1 ml/min/kg, p=NS for both) or increases in DeltaPCO(2) (7+/-7 vs 10+/-8, p=NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6+/-0.3 vs 2.5+/-0.7 and 1.4+/-0.4 vs. 2.9+/-1.1 mmol/l, p=NS between groups).


CONCLUSIONS
Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.
Dubin
Arnaldo
A
Cátedra de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 42 No 577, 1900, La Plata, Argentina. arnaldodubin@speedy.com.ar
Murias
Gastón
G
Sottile
Juan Pablo
JP
Pozo
Mario Omar
MO
Barán
Marcelo
M
Edul
Vanina Siham Kanoore
VS
Canales
Héctor Saúl
HS
Etcheverry
Graciela
G
Maskin
Bernardo
B
Estenssoro
Elisa
E
D000138:Acidosis / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004280:Dobutamine / Q000494:pharmacology; D019446:Endotoxemia / Q000188:drug therapy; D006835:Hydrazones / Q000494:pharmacology* / Q000627:therapeutic use; D019344:Lactic Acid / Q000097:blood; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy*; D000077464:Simendan; D013152:Splanchnic Circulation / Q000187:drug effects*
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D019344:Lactic Acid; D000077464:Simendan; D004280:Dobutamine; D010100:Oxygen