Thoracic Epidural Anesthesia Decreases Endotoxin-Induced Endothelial Injury

Fabian Enigk; Antje Wagner; Rudi Samapati; Heike Rittner; Alexander Brack; Shaaban A Mousa; Michael Schäfer; Helmut Habazettl; Jörn Schäper

Disclosures

BMC Anesthesiol. 2014;14(23)

Abstract and Introduction

Abstract

Background: The sympathetic nervous system is considered to modulate the endotoxin-induced activation of immune cells. Here we investigate whether thoracic epidural anesthesia with its regional symapathetic blocking effect alters endotoxin-induced leukocyte-endothelium activation and interaction with subsequent endothelial injury.

Methods: Sprague Dawley rats were anesthetized, cannulated and hemodynamically monitored. E. coli lipopolysaccharide (Serotype 0127:B8, 1.5 mg x kg⁻¹ x h⁻¹) or isotonic saline (controls) was infused for 300 minutes. An epidural catheter was inserted for continuous application of lidocaine or normal saline in endotoxemic animals and saline in controls. After 300 minutes we measured catecholamine and cytokine plasma concentrations, adhesion molecule expression, leukocyte adhesion, and intestinal tissue edema.

Results: In endotoxemic animals with epidural saline, LPS significantly increased the interleukin-1β plasma concentration (48%), the expression of endothelial adhesion molecules E-selectin (34%) and ICAM-1 (42%), and the number of adherent leukocytes (40%) with an increase in intestinal myeloperoxidase activity (26%) and tissue edema (75%) when compared to healthy controls. In endotoxemic animals with epidural infusion of lidocaine the values were similar to those in control animals, while epinephrine plasma concentration was 32% lower compared to endotoxemic animals with epidural saline.

Conclusions: Thoracic epidural anesthesia attenuated the endotoxin-induced increase of IL-1β concentration, adhesion molecule expression and leukocyte-adhesion with subsequent endothelial injury. A potential mechanism is the reduction in the plasma concentration of epinephrine.

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Abstract and Introduction
Background
Methods
Results
Discussion
Conclusion
References

Table 1. Laboratory variables
Variable	Group	Baseline	5 h LPS	p-value
pH	LPS - TEA -	7.36 [7.33,7.38]	7.30 [7.26,7.32]
	LPS + TEA -	7.36 [7.34,7.39]	7.30 [7.28,7.34] €	€ 0.019
	LPS + TEA +	7.37 [7.34,7.40]	7.32 [7.29,7.45]
p _a CO ₂ (mmHg)	LPS - TEA -	49 [45,51]	46 [42,50]
	LPS + TEA -	45 [37,48]	30 [27,36] € *	€ < 0.001
	LPS + TEA +	47 [45,50]	37 [30,40] € *	€ < 0.001
p _a O ₂ (mm Hg)	LPS - TEA -	72 [64,81]	89 [67,94] €	€ 0.016
	LPS + TEA -	79 [73, 86]	101 [96, 105] € *	€ < 0.001
	LPS + TEA +	78 [66,83]	95.5 [85,104] €	€ < 0.001
Hematocrit (%)	LPS - TEA -	48 [44,50]	46 [41,47] €	€ 0.024
	LPS + TEA -	47 [46,49]	36 [34,39] € *	€ < 0.001
	LPS + TEA +	49 [46,51]	36 [35,37] € *	€ < 0.001
Base excess (mM)	LPS - TEA -	−0.4 [−0.9,0.5]	−4.5 [−6.1,−1.9] € §	€ < 0.001
	LPS + TEA -	−1.6 [−2.7,−0.5]	−9.7 [−11.8,−7.2] €	€ < 0.001
	LPS + TEA +	0.4 [−0.5,1.7] $	−6.8 [−8.7,−4.2] € §	€ < 0.001
Leukocytes (10 ³ μl ^-1 )	LPS - TEA -	9.5 [8.4,11.8]	18.5 [15.6,19.7] €	€ < 0.001
	LPS + TEA -	12.0 [10.6,13.9]	4.4 [3.4,5.9] € *	€ < 0.001
	LPS + TEA +	9.2 [8.0,11.7]	5.3 [3.3,6.6] € *	€ < 0.001
Platelets (10 ³ μl ^-1 )	LPS - TEA -	995 [843,1109]	867 [724,997] €	€ 0.002
	LPS + TEA -	919 [827,1053]	120 [97,204] € *	€ < 0.001
	LPS + TEA +	941 [807,1030]	165 [94,379] € *	€ < 0.001
Sodium (mM)	LPS - TEA -	141 [139,143]	141 [139,143]
	LPS + TEA -	142 [141,143]	142 [141,144]
	LPS + TEA +	141 [140,142]	141 [140,143]
Potassium (mM)	LPS - TEA -	4.4 [4.3,4.7]	4.0 [4.0,4.3] €	€ 0.003
	LPS + TEA -	4.5 [4.3,4.8]	4.6 [4.2,4.9] *
	LPS + TEA +	4.4 [4.3,5.1]	4.3 [4.1,4.5]

LPS = lipopolysaccharide, p_aCO₂ = arterial partial pressure of carbon dioxide, p_aCO₂ = arterial partial pressure of oxygen, TEA = thoracic epidural anesthesia.
Data are median [quartiles], € p-values as depicted in the table vs. baseline, *p < 0.05 vs. LPS - TEA -; $ p < 0.05 vs. LPS + TEA -, § p < 0.05 versus LPS + TEA -.

Table 2. Plasma concentrations of catecholamines and cytokines
Variable	LPS - TEA -	LPS + TEA -	LPS + TEA +
Norepinephrine [ng/l]	2979 [2528,3826]	4543 [3750,5458]	5052 [2902,7252]
Epinephrine [ng/l]	293 [162,496]	901 [568,1628] #	614 [488,1078]
IL-1β [pg/ml]	29.3 [19.7,37.8]	59.9 [54.0,67.7] *	47.7 [32.0,57.5
TNF-α [pg/ml]	16.0 [14.3,17.7]	17.6 [15.7,19.4]	19.6 [18.0,25.8]

Plasma concentrations of catecholamines and cytokines at the end of the experiment. LPS = lipopolysaccharide, TEA = thoracic epidural anesthesia.
IL-1β = interleukin-1β, TNF-α = tumor necrosis factor-α. Data are median [quartiles], # p<0.05 vs. LPS - TEA - and LPS+ TEA +; * p< 0.05 vs. LPS - TEA -.