Immunomodulatory effects of esmolol in a septic animal model due to multidrug-resistant Pseudomonas aeruginosapyelonephritis

Introduction

The infusion of esmolol (a hypelective β₁-blocker) is associated with immunomodulatory effects [1].

Methods

Eighty white rabbits underwent pyelonephritis (multidrug-resistant Pseudomonas aeruginosa) induction and classification in pretreatment (PT) (n = 40) (infusion of esmolol immediately after pyelonephritis induction) and treatment (T) (n = 40) (initial infusion of esmolol 2 hours after pyelonephritis induction) group. PT = group A (n = 10, control, N/S 0.9% infusion), group B (n = 10, esmolol infusion), group C (n = 10, amikacin infusion) and group D (n = 10, esmolol and amikacin infusion) and T = groups E, F, G and H having similar treatment. Serum malondialdehyde (MDA) was estimated at serial time intervals by the thiobarbiturate assay followed by HPLC analysis. The animals were under survival follow-up every 12 hours for the next 21 days. After death, quantitative organ cultures were performed.

Results

Median (IQR) MDA at 24 hours was 1.95 (0.75), 0.78 (1.79), 1.55 (1.60) and 0.12 (0.24) μmol/ml in groups A, B, C and D, respectively. Respective values at 48 hours were 2.60 (2.00), 1.40 (2.36), 3.15 (3.00) and 0.25 (0.20) μmol/ml. At 24 hours, the median (IQR) MDA of groups E, F, G and H were 2.80 (5.74), 0.32 (0.87), 0.61 (5.83) and 0.19 (2.75) μmol/ml, respectively. Tissue bacterial load was similar within groups. See Figures 1 and 2.

Figure 1

Pretreatment group.

Figure 2

Treatment group.

Conclusion

In the present septic model, esmolol prolonged survival probably by exerting an immunomodulatory effect as assessed by reduced oxidative stress without any effect on tissue bacterial load.