TY  - JOUR
A1  - Schick, Martin Alexander
A1  - Baar, Wolfgang
A1  - Bruno, Raphael Romano
A1  - Wollborn, Jakob
A1  - Held, Christopher
A1  - Schneider, Reinhard
A1  - Flemming, Sven
A1  - Schlegel, Nicolas
A1  - Roewer, Norbert
A1  - Neuhaus, Winfried
A1  - Wunder, Christian
T1  - Balanced hydroxyethylstarch (HES 130/0.4) impairs kidney function in-vivo without inflammation
JF  - PLoS One
N2  - Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6h. After 24h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1–4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion
KW  - colloids
KW  - kidneys
KW  - histopathology
KW  - blood
KW  - creatinine
KW  - sepsis
KW  - urine
KW  - inflammation
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126068
VL  - 10
IS  - 9
ER  - 
TY  - JOUR
A1  - Thal, Serge C.
A1  - Smetak, Manuel
A1  - Hayashi, Kentaro
A1  - Förster, Carola Y.
T1  - Hemorrhagic cerebral insults and secondary Takotsubo syndrome: findings in a novel in vitro model using human blood samples
JF  - International Journal of Molecular Sciences
N2  - Intracranial hemorrhage results in devastating forms of cerebral damage. Frequently, these results also present with cardiac dysfunction ranging from ECG changes to Takotsubo syndrome (TTS). This suggests that intracranial bleeding due to subarachnoid hemorrhage (SAH) disrupts the neuro–cardiac axis leading to neurogenic stress cardiomyopathy (NSC) of different degrees. Following this notion, SAH and secondary TTS could be directly linked, thus contributing to poor outcomes. We set out to test if blood circulation is the driver of the brain–heart axis by investigating serum samples of TTS patients. We present a novel in vitro model combining SAH and secondary TTS to mimic the effects of blood or serum, respectively, on blood–brain barrier (BBB) integrity using in vitro monolayers of an established murine model. We consistently demonstrated decreased monolayer integrity and confirmed reduced Claudin-5 and Occludin levels by RT-qPCR and Western blot and morphological reorganization of actin filaments in endothelial cells. Both tight junction proteins show a time-dependent reduction. Our findings highlight a faster and more prominent disintegration of BBB in the presence of TTS and support the importance of the bloodstream as a causal link between intracerebral bleeding and cardiac dysfunction. This may represent potential targets for future therapeutic inventions in SAH and TTS.
KW  - Takotsubo syndrome
KW  - subarachnoid hemorrhage
KW  - inflammation
KW  - in vitro
KW  - blood
KW  - blood–brain barrier
KW  - human
KW  - patient
KW  - endothelial cells
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288305
SN  - 1422-0067
VL  - 23
IS  - 19
ER  -