Article
Long-term inhibitory effect of s-ketamine on spreading depolarisations in a KCl model and a MCA occlusion model in the gyrencephalic swine brain
Langzeithemmende Wirkung von s-Ketamin auf die Ausbreitung von Depolarisationen in einem KCl-Modell und einem MCA-Okklusionsmodell im gyrencephalen Schweinehirn
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Authors
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Renan Sánchez-Porras
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Modar Kentar
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Arturo Olivares-Rivera
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Lorenz Uhlmann
- Ruprecht-Karls-University Heidelberg, Institute of Medical Biometry and Informatics, Heidelberg, Deutschland
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Kevin Kunzmann
- Ruprecht-Karls-University Heidelberg, Institute of Medical Biometry and Informatics, Heidelberg, Deutschland
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Martina Mann
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Roland Zerelles
- Universitätsklinikum Heidelberg, Neurologische Klinik, Heidelberg, Deutschland
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Adrian Hernandez-Aguilera
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Mildred Gutierrez-Herrera
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Edgar Santos
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
| Published: | June 4, 2021 |
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Outline
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Objective: We investigated the long-term effect of s-ketamine on SD characteristics in two gyrencephalic swine brain models.
Methods: A total of 27 female German landrace swines were used for this study. For this purpose, two gyrencephalic swine brain models were applied. In one model, SDs were elicited through topical application of KCl onto the cerebral cortex (n=15); in the other model (n=12), SDs were spontaneously induced after the occlusion of the middle cerebral artery (MCAo). A total of 15 animals were used in the KCl experimental model. These animals were divided into 3 groups: one control group and two s-ketamine groups. S-ketamine was either perfused at a dose of 2mg/kg BW/h or at a dose of 4mg/kg BW/h for a period of 18h. In the MCAo model 12 animals were used. These animals were divided into two groups of 6 animals, each: a control group and an s-ketamine group. S-ketamine was perfused at a dose of 5mg/kg BW/h for a period of 18h.
Results: We were able to corroborate that doses of s-ketamine above the therapeutically recommended (2mg/kg /BW/h) are needed to reduce SDs over a prolonged period of time of 18h. In particular, higher doses of s-ketamine are needed for injury-induced SDs than for KCl-induced SDs in order to achieve a similar effect. Our data shows that s-ketamine considerably reduces SD incidence and its expansion during its long-term administration. However, no clear effect on SD amplitude and propagation speed was observed in the stroke model during the same monitoring time, still an effect in these two properties was found in the KCl model. Notably, we did not find clear evidence for the development of tolerance against s-ketamine in the swine brain during the time of administration in either of the models.
Conclusion: Our results indicate that the long-term administration of s-ketamine at human equivalent doses is capable of interfering with SD development in the gyrencepahlic swine brain. Administration of s-ketamine over prolong periods did not lose efficacy against SDs. S-ketamine may be a therapeutically effective option to reduce SDs over prolong periods of time.
Figure 1 [Fig. 1]
