TY  - JOUR
A1  - Wollborn, Jakob
A1  - Wunder, Christian
A1  - Stix, Jana
A1  - Neuhaus, Winfried
A1  - Bruno, Rapahel R.
A1  - Baar, Wolfgang
A1  - Flemming, Sven
A1  - Roewer, Norbert
A1  - Schlegel, Nicolas
A1  - Schick, Martin A.
T1  - Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression
JF  - Journal of Pharmacology and Pharmacotherapeutics
N2  - Objective: To investigate the impact of the phophodiesterase-4 inhibition (PD-4-I) with rolipram on hepatic integrity in lipopolysaccharide (LPS) induced hyperinflammation. Materials and Methods: Liver microcirculation in rats was obtained using intravital microscopy. Macrohemodynamic parameters, blood assays, and organs were harvested to determine organ function and injury. Hyperinflammation was induced by LPS and PD-4-I rolipram was administered intravenously one hour after LPS application. Cell viability of HepG2 cells was measured by EZ4U-kit based on the dye XTT. Experiments were carried out assessing the influence of different concentrations of tumor necrosis factor alpha (TNF-α) and LPS with or without PD-4-I. Results: Untreated LPS-induced rats showed significantly decreased liver microcirculation and increased hepatic cell death, whereas LPS + PD-4-I treatment could improve hepatic volumetric flow and cell death to control level whithout influencing the inflammatory impact. In HepG2 cells TNF-α and LPS significantly reduced cell viability. Coincubation with PD-4-I increased HepG2 viability to control levels. The heme oxygenase 1 (HO-1) pathway did not induce the protective effect of PD-4-I. Conclusion: Intravenous PD-4-I treatment was effective in improving hepatic microcirculation and hepatic integrity, while it had a direct protective effect on HepG2 viability during inflammation.
KW  - acute liver failure
KW  - endotoxemia
KW  - phosphodiesterase
KW  - rolipram
KW  - sepsis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149336
VL  - 6
IS  - 1
ER  - 
TY  - JOUR
A1  - Enigk, Fabian
A1  - Wagner, Antje
A1  - Samapati, Rudi
A1  - Rittner, Heike
A1  - Brack, Alexander
A1  - Mousa, Shaaban A.
A1  - Schäfer, Michael
A1  - Habazettl, Helmut
A1  - Schäper, Jörn
T1  - Thoracic epidural anesthesia decreases endotoxin-induced endothelial injury
JF  - BMC Anesthesiology
N2  - 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-1 beta 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-1 beta concentration, adhesion molecule expression and leukocyte-adhesion with subsequent endothelial injury. A potential mechanism is the reduction in the plasma concentration of epinephrine.
KW  - endotoxemia
KW  - myeloperoxidase
KW  - endothelial injury
KW  - adhesion molecules
KW  - inflammatory response
KW  - intestinal microvascular perfusion
KW  - cell-adhesion
KW  - induced impairment
KW  - reperfusion injury
KW  - sepsis
KW  - neutrophil
KW  - lidocaine
KW  - lung injury
KW  - cytokines
KW  - epidural anesthesia
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116787
VL  - 14
IS  - 23
ER  -