Dose-related effects of dexmedetomidine on sepsis-initiated lung injury in rats

Abstract

Background

Sepsis is one of the leading causes of death in intensive care units. Dexmedetomidine is a sedative agent with anti-inflammatory properties. This study is designed to differentiate the impact of two different doses of dexmedetomidine on lung injury induced by sepsis.

Methods

Adult male Wistar rats were randomly divided into four groups: sham (n = 6), control (n = 12), 5DEX (n = 12), and 10DEX (n = 12). Cecal ligation puncture (CLP) was applied for sepsis initiation. The 5DEX group received 5 µg.kg^-1.h^-1 and the 10DEX group received 10 µg.kg^-1.h^-1 dexmedetomidine intravenous infusions for a 1-hour period. Six hours after CLP, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and intercellular adhesion molecule-1 (ICAM-1) levels were analyzed in blood samples. Twenty-four hours after CLP, lung samples from the remaining rats were collected for the measurement of myeloperoxidase (MPO) activity, histological examination, and TdT- (terminal deoxynucleotidyl transferase) mediated fluorescent-dUTP labeling staining for apoptosis detection.

Results

Serum cytokine release, MPO activity, and apoptosis in the lung were significantly increased in the CLP group compared with the sham and dexmedetomidine groups (p < 0.05). TNF-α, ICAM-1, and MPO were significantly lower in the 10DEX group compared with both 5DEX and control groups, while IL-1β, total injury score, and apoptotic cell count had significantly lower values in both 10DEX and 5DEX groups compared with the control group (p < 0.05).

Conclusion

Dexmedetomidine administration played a protective role against CLP-induced lung injury. High-dose dexmedetomidine was needed for suppressing the leukocyte-mediated lung injury and apoptosis of lung tissue.

KEYWORDS
Sepsis; Lung injury; Dexmedetomidine