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Our study set out to investigate in an exploratory approach the interaction between NO and energy metabolism following SAH as both hypoxia and inflammation are known to affect nitric oxide (NO) metabolism and NO in turn affects mitochondria.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In seven patients under continuous multimodality neuromonitoring suffering poor-grade aneurysmal SAH, cerebral metabolism and NO levels (determined as a sum of nitrite plus nitrate) were determined in cerebral microdialysate for 14 days following SAH. In additional ex vivo experiments, rat cortex homogenate was subjected to the NO concentrations determined in SAH patients to test whether these NO concentrations impair mitochondrial function (determined by means of high-resolution respirometry).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>NO levels showed biphasic kinetics with drastically increased levels during the first 7 days (74.5 \u00b1 29.9 \u03bcM) and significantly lower levels thereafter (47.5 \u00b1 18.7 \u03bcM; <jats:italic>p<\/jats:italic> = 0.02). Only during the first 7 days, NO levels showed a strong negative correlation with brain tissue oxygen tension (<jats:italic>r<\/jats:italic> = \u2212 0.78; <jats:italic>p<\/jats:italic> &lt; 0.001) and a positive correlation with cerebral lactate (<jats:italic>r<\/jats:italic> = 0.79; <jats:italic>p<\/jats:italic> &lt; 0.001), pyruvate (<jats:italic>r<\/jats:italic> = 0.68; <jats:italic>p<\/jats:italic> &lt; 0.001), glutamate (<jats:italic>r<\/jats:italic> = 0.65; <jats:italic>p<\/jats:italic> &lt; 0.001), as well as the lactate-pyruvate ratio (<jats:italic>r<\/jats:italic> = 0.48; <jats:italic>p<\/jats:italic> = 0.01), suggesting mitochondrial dysfunction. Ex vivo experiments confirmed that the increase in NO levels determined in patients during the acute phase is sufficient to impair mitochondrial function (<jats:italic>p<\/jats:italic> &lt; 0.001). Mitochondrial respiration was inhibited irrespectively of whether glutamate (substrate of complex I) or succinate (substrate of complex II) was used as mitochondrial substrate suggesting the inhibition of mitochondrial complex IV. The latter was confirmed by direct determination of complex IV activity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Exploratory analysis of our data suggests that during the acute phase of SAH, NO plays a key role in the neuronal damage impairing mitochondrial function and facilitating accumulation of mitochondrial substrate; further studies are required to understand mechanisms underlying this observation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00701-020-04536-x","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T00:02:23Z","timestamp":1598313743000},"page":"139-149","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cerebral nitric oxide and mitochondrial function in patients suffering aneurysmal subarachnoid hemorrhage\u2014a translational approach"],"prefix":"10.1007","volume":"163","author":[{"given":"Arthur","family":"Hosmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja","family":"Milivojev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergiu","family":"Dumitrescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Reinprecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelheid","family":"Weidinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-4997","authenticated-orcid":false,"given":"Andrey V.","family":"Kozlov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,25]]},"reference":[{"issue":"3","key":"4536_CR1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/0006-291X(89)92258-4","volume":"159","author":"T Asano","year":"1989","unstructured":"Asano T, Ikegaki I, Suzuki Y, Satoh S, Shibuya M (1989) Endothelin and the production of cerebral vasospasm in dogs. 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