Artikel
Levosimendan as therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid haemorrhage?
Levosimendan als therapeutische Strategie zur Vorbeugung von Neuroinflammation nach aneurysmaler Subarachnoidalblutung?
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Veröffentlicht: | 4. Juni 2021 |
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Objective: Poor patients’ outcome after aneurysmal subarachnoid haemorrhage (SAH) is owed a multifactorial process, mainly including cerebral inflammation (CI), breakdown of cerebral autoregulation, delayed cerebral vasospasm (DCVS) and delayed cerebral ischemia (DCI) followed by neurodegeneration. CI is mainly triggered by enhanced synthesis of serotonin (5-HT), prostaglandin F2alpha (PGF2a) and cytokines such as interleukines. Levosimendan (LV), a calcium-channel sensitizer, was already shown to display anti-inflammatory effects in patients with severe heart failure. Therefore, we wanted to elucidate its potential anti-inflammatory role on cerebrovasculature after SAH.
Methods: Experimental SAH was inducted by using a modified double-haemorrhage rat model. Autologous blood was taken and injected into the cisterna magna on day 1 and 2. Sham animals received injection of isotonic 0.9 % saline, instead. Sprague-Dawley rats were sacrificed on day 3 and 5 after SAH or sham operation. The vasospastic basilar artery was carefully dissected from the brain stem and further used for isometric investigations of the vessel tone in an organ bath. Vessel segments were either preincubated with LV (10-4 M) or without. Precontraction was performed with 5-HT (10-9 M – 10-5 M) or PGF2a (3 x 10-5 M) followed by application of an acetylcholine- (ACh) (10-8 M – 10-4 M) or LV-series (10-8 M – 3 x 10-4 M).
Results: After preincubation with LV and 5-HT-precontraction ACh-series showed a strong vasorelaxation. Interestingly, SAH D3 and D5 vessel segments showed a higher vasorelaxation compared to sham-operated animals. The application of a LV-series after prior PGF2a precontraction of the arterial ring segments showed a significant enhanced relaxation in sham- (p = 0.004) and SAH-animals (p = 0.0008), compared to a solvent control group without LV.
Conclusion: LV administration after SAH seems to beneficially influence DCVS by antagonizing inflammatory microenvironment characterized by 5-HT and PGF2a. A 5-HT- and PGF2a-mediated vasocontraction was notably reduced after experimental induced SAH. Considering these spasmolytic and anti-inflammatory effects, LV might possess a role in the treatment of SAH, even more in the treatment of Tako-Tsubo-Cardiomyopathy, where the use of catecholamine inotropes is contradicted.