Key result
Antecedent administration of epinephrine in a rat sepsis model significantly inhibited the production of TNF-α compared to LPS alone (164.8 vs 459.8 pg/mL, p<0.001), possibly via the β2-adrenoceptor.
Why the study?
Does antecedent epinephrine alter heart rate variability and cytokine levels in a rat sepsis model?
Does antecedent epinephrine alter heart rate variability and cytokine levels in a rat sepsis model?
Absolute Event Rate: 164.8% vs 459.8%
p-value: p=<0.001
Antecedent epinephrine administration in a rat sepsis model inhibits TNF-α production, likely via β2-adrenoceptors.
Antecedent EPI attenuates TNF-α via β-adrenoceptors in rat sepsis; hypothesis-generating for autonomic-cytokine modulation before clinical trials.
Catecholamines have both anti-inflammatory and vasoactive properties. A decreased cardiac response to catecholamines has been associated with a high risk of death in sepsis and septic shock. The aim of this study was to investigate the effects of epinephrine (EPI) on heart rate variability (HRV) and autonomic balance, as well as cytokine levels, in a rat sepsis model. Thirty-six male Sprague-Dawley rats were assigned to 4 experimental groups and 2 control groups of 6 rats each. The rats in the experimental groups were inoculated with a lipopolysaccharide (LPS, endotoxin) to establish a sepsis model. Group A received only LPS; group B received LPS, antecedent EPI and the nonselective β-blocker propranolol; group C received LPS and antecedent EPI; and group D received LPS, antecedent EPI and the selective β1-blocker esmolol. One control group received EPI and the other received saline placebo. Heart rate variability (HRV) was analyzed and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were measured. Measurements were carried out at baseline, at 0 hour after EPI infusion, and at 0.5, 2, and 4 hours after LPS inoculation. There were significant differences in HRV and cytokine levels between the groups, indicating that LPS infusion caused autonomic imbalance. Antecedent EPI significantly decreased the level of TNF-α in group C compared with group A in which TNF-α level peaked at 2 hours and then declined. Propranolol (group B) but not esmolol (group D) administration resulted in elevated TNF-α levels, comparable to those observed in group A. In conclusion, antecedent administration of EPI in a rat sepsis model inhibits the production of TNF-α possibly via the β2-adrenoceptor.
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Chang et al. (2018) studied Sepsis (LPS-induced model) (n=36). Epinephrine vs. LPS alone (no epinephrine) was evaluated on TNF-α level at 2 hours after LPS inoculation (pg/mL) (p=<0.001). Antecedent administration of epinephrine in a rat sepsis model significantly inhibited the production of TNF-α compared to LPS alone (164.8 vs 459.8 pg/mL, p<0.001), possibly via the β2-adrenoceptor.
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