Study of the effect of C1-esterase inhibitor administration to the sepsis pig model

Background

New therapy is required that improves the prognosis of patients suffering from severe sepsis or septic shock. C1-esterase inhibitor (C1-Inh) was introduced in clinical medicine for patients with hereditary angioedema. Some studies show that C1-Inh administration may also have a beneficial effect in other clinical conditions such as sepsis [1, 2]. We examined the effect of C1-Inh administration to the sepsis pig model.

Materials and methods

The experiments were performed divided into two groups: the treatment group and the control group. We administered LPS (40 μg/kg) to pigs of about 10 kg over 30 minutes. At the same time, we administered C1-Inh in the control group (500 U, n = 3; 1,000 U, n = 3), and saline in the control group (n = 3). We examined the effect of C1-Inh for the outcome of the two groups, physiological indicators such as heart rates (HR) and mean arterial pressure (MAP), and autopsy results such as pleural effusion and ascites.

Results

The outcome of the two groups was that 5/6 in the treatment group and 2/3 in the control group survived at 240 minutes from the end of LPS administration. HR (/minute) at 180 minutes from the end of LPS administration was 157.5 ± 12.3 in the treatment group and 205.3 ± 42.6 in the control group, and MAP (mmHg) at the same time was 60.0 ± 8.2 in the treatment group and 58.3 ± 5.6 in the control group. As for the autopsy results, pleural effusion (ml) was 13.28 ± 3.13 in the treatment group and 9.87 ± 4.33 in the control group, and ascites (ml) was 165.8 ± 32.99 in the treatment group and 210.0 ± 60.8 in the control group. Seeing each individual, the individual showing a large effect of C1-inh was observed.

Conclusions

C1-Inh tended to stabilize the hemodynamics of the sepsis pig model, but was not able to reduce significantly the amount of pleural effusion and ascites.