Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats.
OBJECTIVE
Vasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 microg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr).


METHODS
Prospective, randomized, controlled experimental study with repeated measures.


METHODS
Investigational animal laboratory.


METHODS
A total of 77 rats were divided into five groups: group C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats).


METHODS
Rats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of >90 mm Hg and aortic blood flow at baseline values.


RESULTS
Terlipressin significantly (p <.05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p <.05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p <.05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET).


CONCLUSIONS
Low-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.
Asfar
Pierre
P
Laboratoire HIFIH, Université d'Angers, France.
Pierrot
Marc
M
Veal
Nary
N
Moal
Frédéric
F
Oberti
Frédéric
F
Croquet
Vincent
V
Douay
Olivier
O
Gallois
Yves
Y
Saumet
Jean-Louis
JL
Alquier
Philippe
P
Calès
Paul
P
D000818:Animals; D006439:Hemodynamics / Q000187:drug effects*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy*; D013152:Splanchnic Circulation / Q000187:drug effects*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use*
D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin