Related Experiment Video
Updated: Aug 15, 2026
Cecal Ligation Puncture Procedure
Published on: May 7, 2011
N(G)-monomethyl-L-arginine improves survival in a pig model of abdominal sepsis
O A Strand1, A M Leone, K E Giercksky
1Department of Infectious Diseases, Institute for Experimental Medical Research, Ullevål University Hospital, Oslo, Norway.
Objective:
To test the effect of a continuous infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on survival rate and hemodynamics in a pig model of endogenous peritoneal live bacterial sepsis.
Design:
Prospective, randomized trial.
Setting:
Laboratory at a university medical center.
Subjects:
Thirty-five pigs with an average weight of 26 kg (range 21 to 33).
Interventions:
After surgical preparation, animals (control, n=6) given anesthesia and fluids were observed for 9 hrs. Fifteen experimental animals received 0.5 g of cecal content/kg of body weight intraperitoneally after surgery. Nine of these animals received standard anesthesia and fluids and were observed for 9 hrs or until death. Six animals received a continuous infusion of L-NMMA (10 mg/kg/hr) 3 hrs after sepsis induction. Starting 3 hrs after surgery, five nonrandomized animals were given anesthesia and fluids and received a 6-hr continuous infusion of L-NMMA (10 mg/kg/hr). An additional nine animals were anesthetized and blood samples were taken to determine plasma nitrate concentrations in nonoperated pigs.
Measurements And Main Results:
L-NMMA treatment increased 9-hr survival in septic animals from 11% to 83% (p < .001), prevented a further decrease in mean arterial pressure and restored mean arterial pressure to control levels (p < .00002 vs. nontreated septic animals). Mean pulmonary arterial pressure increased slightly during L-NMMA infusion (p < .0003). Coronary blood flow was preserved during L-NMMA treatment. Cardiac index and urine production reached and maintained control levels during L-NMMA treatment of septic animals. Mean central venous pH did not deteriorate during L-NMMA treatment. Animals treated with L-NMMA had plasma nitrate concentrations similar to nonseptic control animals. The results from the nonseptic control group receiving L-NMMA suggest that a substantial part of the effect of L-NMMA in this model of septic shock may be due to inhibition of the constitutive nitric oxide production.
Conclusions:
In this porcine model of peritoneal sepsis, infusion of L-NMMA increased survival rate and maintained mean arterial pressure without worsening tissue oxygenation. Coronary blood flow, cardiac index, systemic vascular resistance, and urine production were well maintained during L-NMMA treatment.
Insights
Continuous infusion of N(G)-monomethyl-L-arginine (L-NMMA) significantly improved survival rates in a pig model of sepsis. L-NMMA treatment also stabilized mean arterial pressure and maintained vital organ function during septic shock.
Area of Science:
- Physiology
- Pharmacology
- Critical Care Medicine
Background:
- Sepsis-induced hypotension and organ dysfunction remain critical challenges.
- Nitric oxide (NO) plays a complex role in sepsis, with both beneficial and detrimental effects.
- Inhibiting NO synthase may offer a therapeutic strategy for septic shock.
Purpose of the Study:
- To evaluate the efficacy of continuous N(G)-monomethyl-L-arginine (L-NMMA) infusion on survival and hemodynamics in a porcine model of endogenous peritoneal bacterial sepsis.
- To investigate the impact of L-NMMA on mean arterial pressure, cardiac index, and tissue oxygenation during sepsis.
Main Methods:
- Prospective, randomized trial involving 35 pigs.
- Sepsis was induced by intraperitoneal injection of cecal content.
- Experimental groups received either standard care or continuous L-NMMA infusion (10 mg/kg/hr) starting 3 hours post-sepsis induction.
Main Results:
- L-NMMA treatment increased 9-hour survival from 11% to 83% (p < .001).
- L-NMMA prevented a drop in mean arterial pressure and restored it to control levels (p < .00002).
- Cardiac index, urine production, and coronary blood flow were preserved, and central venous pH remained stable.
Conclusions:
- Continuous L-NMMA infusion is a promising therapeutic intervention for porcine peritoneal sepsis.
- L-NMMA effectively improves survival and maintains hemodynamic stability without compromising tissue oxygenation.
- The findings suggest that inhibiting constitutive nitric oxide production contributes to L-NMMA's beneficial effects in septic shock.
