Stefan Wanderer, Lukas Andereggen, Jan Mrosek, Sepide Kashefiolasl, Gerrit Alexander Schubert, Serge Marbacher, Jürgen Konczalla
Journal of neurointerventional surgery 2022 AprPoor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration. CI is mainly triggered by enhanced synthesis of serotonin (5-HT), prostaglandin F2alpha (PGF2a), and cytokines such as interleukins. Levosimendan (LV), a calcium-channel sensitizer, has already displayed anti-inflammatory effects in patients with severe heart failure. Therefore, we wanted to elucidate its potential anti-inflammatory role on the cerebral vasculature after SAH. Experimental SAH was induced by using an experimental double-hemorrhage model. Sprague Dawley rats were harvested on day 3 and day 5 after the ictus. The basilar artery was used for isometric investigations of the muscular media tone. Vessel segments were either preincubated with LV or without, with precontraction performed with 5-HT or PGF2a followed by application of acetylcholine (ACh) or LV. After preincubation with LV 10-4 M and 5-HT precontraction, ACh triggered a strong vasorelaxation in sham segments (LV 10-4 M, Emax 65%; LV 10-5 M, Emax 48%; no LV, Emax 53%). Interestingly, SAH D3 (LV 10-4, Emax 76%) and D5 (LV 10-4, Emax 79%) segments showed greater vasorelaxation compared with sham. An LV series after PGF2a precontraction showed significantly enhanced relaxation in the sham (P=0.004) and SAH groups (P=0.0008) compared with solvent control vessels. LV application after SAH seems to beneficially influence DCVS by antagonizing 5-HT- and PGF2a-triggered vasoconstriction. Considering this spasmolytic effect, LV might have a role in the treatment of SAH, additionally in selected patients suffering takotsubo cardiomyopathy. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Stefan Wanderer, Lukas Andereggen, Jan Mrosek, Sepide Kashefiolasl, Gerrit Alexander Schubert, Serge Marbacher, Jürgen Konczalla. Levosimendan as a therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid hemorrhage? Journal of neurointerventional surgery. 2022 Apr;14(4):408-412
PMID: 34039684
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