TY  - JOUR
A1  - Haarmann, Axel
A1  - Vollmuth, Christoph
A1  - Kollikowski, Alexander M.
A1  - Heuschmann, Peter U.
A1  - Pham, Mirko
A1  - Stoll, Guido
A1  - Neugebauer, Hermann
A1  - Schuhmann, Michael K.
T1  - Vasoactive soluble endoglin: a novel biomarker indicative of reperfusion after cerebral large-vessel occlusion
JF  - Cells
N2  - Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion.
KW  - endoglin
KW  - brain endothelium
KW  - stroke
KW  - shedding
KW  - mechanical thrombectomy
KW  - hypoxia
KW  - reperfusion injury
KW  - biomarker
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304995
SN  - 2073-4409
VL  - 12
IS  - 2
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  -