Effects of terlipressin on microcirculation of small bowel mesentery in rats with endotoxic shock

J Surg Res. 2014 May 15;188(2):503-9. doi: 10.1016/j.jss.2014.01.053. Epub 2014 Feb 3.

Abstract

Background: Septic shock is still related to unacceptably high morbidity and mortality. Microcirculatory alteration has been demonstrated to be one important reason associated with this evolution. Vasoactive drugs are often used to restore adequate arterial pressure and tissue perfusion in septic shock. To define the roles of different drugs, the effects of terlipressin (TP) on the microcirculation of small bowel mesentery in rats with endotoxic shock were evaluated and compared with those of norepinephrine (NE).

Methods: Twenty-five adult male Wistar rats were randomized to the control (n = 5), TP (n = 10), and NE (n = 10) groups. After endotoxic shock was induced by intravenous lipopolysaccharide administration for 30 min, rats in the NE and TP groups were infused with saline 5 mL/kg/h and simultaneously given NE 4 μg/kg/min or TP 8 μg/kg/h. The mean arterial pressure, heart rate, blood gas analysis, and microvascular blood flow images of small bowel mesentery were recorded.

Results: After fluid resuscitation and vasopressor infusion, the mean arterial pressure was restored to the baseline values in the NE and TP groups. In the TP group, the heart rate was significantly lower compared with the NE group (P = 0.013). The proportion of perfused vessels and the microvascular flow index (MFI) were significantly increased; furthermore, the heterogeneity index of small vessels was markedly decreased in both the interventional groups with respect to the control group. Compared with the NE group, the MFI was significantly higher (P < 0.05) and the heterogeneity index was significantly lower (P < 0.05) in the TP group.

Conclusions: Both TP and NE improved hemodynamic and microcirculatory alterations in rats with endotoxic shock. Compared with NE, TP was more effective in promoting MFI and improving the heterogeneity of small bowel mesentery in rats.

Keywords: Endotoxic shock; Microcirculation; Norepinephrine; Small bowel mesentery; Terlipressin.

MeSH terms

  • Acid-Base Equilibrium
  • Animals
  • Drug Evaluation, Preclinical
  • Hemodynamics
  • Lypressin / analogs & derivatives*
  • Lypressin / pharmacology
  • Lypressin / therapeutic use
  • Male
  • Microcirculation / drug effects*
  • Norepinephrine
  • Oxygen / blood
  • Random Allocation
  • Rats, Wistar
  • Shock, Septic / drug therapy*
  • Shock, Septic / physiopathology
  • Splanchnic Circulation / drug effects*
  • Terlipressin
  • Vasoconstrictor Agents / pharmacology
  • Vasoconstrictor Agents / therapeutic use*

Substances

  • Vasoconstrictor Agents
  • Lypressin
  • Terlipressin
  • Oxygen
  • Norepinephrine