Inotropic support during experimental endotoxemic shock: part I. The effects of levosimendan on splanchnic perfusion.
BACKGROUND
Septic shock may cause splanchnic hypoperfusion. We hypothesized that levosimendan would improve systemic and hepatosplanchnic perfusion during endotoxemic shock.


METHODS
In 16 anesthetized pigs (31.4 +/- 3.4 kg), a jugular vein, a carotid artery, the pulmonary artery (thermodilution), the portal vein, and a hepatic vein were cannulated for hemodynamic monitoring and blood sampling. Ultrasonic flowprobes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery (SMA). In addition to 30 mL/kg of dextran 70 given before baseline, all animals received 10 mL x kg(-1) x h(-1) of IV fluids throughout the experiment. An endotoxin infusion (2 microg x kg(-1) x h(-1)) was given for 300 min; 100 min after the start of endotoxin, the pigs were randomized to receive levosimendan (50 microg x kg(-1) x h(-1), n = 8) or placebo (n = 8). To evaluate the isolated effects of endotoxemia, all data before randomization were pooled into one group. Data were analyzed by analysis of variance and presented as mean +/- sem.


RESULTS
Endotoxemia (t = 90 min, pooled data) decreased systemic vascular resistance (SVR, 2526 +/- 203 to 1946 +/- 122 dyn x s x cm(-5), P = 0.003) and mean arterial blood pressure (MAP, 109 +/- 6 to 84 +/- 3 mm Hg, P < 0.05), whereas heart rate (66 +/- 4 to 98 +/- 8 bpm), and mean pulmonary arterial pressure (MPAP, 20 +/- 1 to 38 +/- 2 mm Hg) increased (P < 0.001). Cardiac output (CO, 3.4 +/- 0.2 L/min) and systemic oxygen delivery (414 +/- 33 mL/min) were unchanged, but blood flows in the SMA (575 +/- 34 to 392 +/- 38 mL/min) and the portal vein (881 +/- 62 to 568 +/- 39 mL/min) decreased (P < 0.001). Although hepatic arterial blood flows increased (36 +/- 8 to 219 +/- 38 mL/min), gut (114 +/- 11 to 84 +/- 7 mL/min) and hepatic (94 +/- 11 to 67 +/- 8 mL/min) oxygen deliveries decreased (P < 0.05). At t = 300 min, the levosimendan group showed lower MPAP (39 +/- 3 vs 49 +/- 2 mm Hg, P = 0.025), lower SVR (2158 +/- 186 vs 3069 +/- 370 dyn x s x cm(-5), P = 0.052), and lower MAP (55 +/- 9 vs 87 +/- 9 mm Hg, P < 0.001) than the control group. In both groups, CO, portal vein, and hepatic arterial blood flows decreased (P < 0.001); the mean values for the levosimendan group at t = 300 min were 2.0 +/- 0.4 L/min, 390 +/- 83 mL/min, and 36 +/- 12 mL/min, respectively. SMA blood flow decreased only in the levosimendan group (432 +/- 40 to 320 +/- 78 mL/min, P < 0.001), whereas gut oxygen delivery decreased in the levosimendan (85 +/- 12 to 63 +/- 12 mL/min, P < 0.001) and in the control (83 +/- 6 to 59 +/- 3 mL/min, P = 0.03) groups.


CONCLUSIONS
Levosimendan administered after the establishment of endotoxemic shock to pigs receiving moderate fluid resuscitation prevented further increases in MPAP and maintained a low SVR. There were, however, no improvements in CO, MAP decreased, and levosimendan neither prevented the development of circulatory shock nor improved hepatosplanchnic perfusion.
Cunha-Goncalves
Doris
D
Heart and Lung Division, Department of Cardiothoracic Surgery, Anesthesia and Intensive Care, Lund University Hospital, SE-221 85 Lund, Sweden. doris.cunha_goncalves@med.lu.s
Perez-de-Sa
Valeria
V
Grins
Edgars
E
Dahm
Peter L
PL
Thörne
Johan
J
Blomquist
Sten
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005440:Fluid Therapy; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006835:Hydrazones / Q000494:pharmacology*; D007022:Hypotension / Q000188:drug therapy / Q000503:physiopathology; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides; D008102:Liver Circulation / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D011724:Pyridazines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D000077464:Simendan; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D002316:Cardiotonic Agents; D006835:Hydrazones; D008070:Lipopolysaccharides; D011724:Pyridazines; C440499:lipopolysaccharide, Escherichia coli O111 B4; D019344:Lactic Acid; D000077464:Simendan; D010100:Oxygen