Spinal cord blood flow elevation with systemic vasopressor noradrenaline is partly mediated by vasodilation of spinal arteries due to reduced expression of alpha adrenoreceptors
Elevation of mean arterial blood pressure (MAP) has been proposed to raise spinal cord blood flow (SCBF) after traumatic spinal cord injury (TSCI). Current clinical guidelines for cervical TSCI suggest maintaining MAP 85–90 mmHg for 5–7 days using vasopressors, eg, noradrenaline. However, it remains...
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| creator | Entezari, Seyar Thygesen, Mathias Møller Staehr, Christian Melnikova, Elizaveta Skov, Mathias Rajanathan, Rajkumar Rasmussen, Mads Rasmussen, Mikkel Mylius Matchkov, Vladimir V. |
| description | Elevation of mean arterial blood pressure (MAP) has been proposed to raise spinal cord blood flow (SCBF) after traumatic spinal cord injury (TSCI). Current clinical guidelines for cervical TSCI suggest maintaining MAP 85–90 mmHg for 5–7 days using vasopressors, eg, noradrenaline. However, it remains unknown whether these interventions that promote an increased systemic MAP result in improved perfusion in the spinal cord. The local effect of vasopressors on the spinal cord arteries also remains unknown.
The aim of this study was to investigate whether the increased systemic MAP results in increased SCBF, and secondly, to examine the mechanism behind noradrenaline (NA) action in spinal cord arteries.
An experimental animal study.
The study included nine 38–42 kg landrace pigs. In six pigs, MAP was gradually elevated using NA and continuous SCBF was recorded by laser doppler flowmetry. Spinal cord samples from these 6 pigs were excised for isolation of spinal cord arteries that were used for ex-vivo vascular function assessment in isometric myograph. Segments of mesentery from another 3 pigs were used to dissect mesenteric small arteries that were also studied in myograph, as control peripheral arteries. Other spinal cord and mesenteric arterial segments from the same biopsies were dissected and snap-frozen for the following expression analysis. Adrenoceptor's expression in arteries of all included animals was assessed with quantitative PCR.
The controlled mixed model found that SCBF was lower at MAP below 50 mmHg and that SCBF increased significantly in the MAP range of 50-100 mmHg (p=.02). Further increase of MAP did not significantly affect SCBF (at MAP range of 100–150 mmHg, p=.15; at 150–200 mmHg, p=.51). However, SCBF significantly increased over the study time-course (at 80 min, p=.002; at 100 min, p |
| doi_str_mv | 10.1016/j.spinee.2024.11.010 |
| format | Article |
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The aim of this study was to investigate whether the increased systemic MAP results in increased SCBF, and secondly, to examine the mechanism behind noradrenaline (NA) action in spinal cord arteries.
An experimental animal study.
The study included nine 38–42 kg landrace pigs. In six pigs, MAP was gradually elevated using NA and continuous SCBF was recorded by laser doppler flowmetry. Spinal cord samples from these 6 pigs were excised for isolation of spinal cord arteries that were used for ex-vivo vascular function assessment in isometric myograph. Segments of mesentery from another 3 pigs were used to dissect mesenteric small arteries that were also studied in myograph, as control peripheral arteries. Other spinal cord and mesenteric arterial segments from the same biopsies were dissected and snap-frozen for the following expression analysis. Adrenoceptor's expression in arteries of all included animals was assessed with quantitative PCR.
The controlled mixed model found that SCBF was lower at MAP below 50 mmHg and that SCBF increased significantly in the MAP range of 50-100 mmHg (p=.02). Further increase of MAP did not significantly affect SCBF (at MAP range of 100–150 mmHg, p=.15; at 150–200 mmHg, p=.51). However, SCBF significantly increased over the study time-course (at 80 min, p=.002; at 100 min, p<.001), which was dependent on the experimental duration being a confounder of increased exposure to large doses of NA. Isolated spinal arteries did not contract to NA ex-vivo and even showed a tendency for vasorelaxation. This relaxation was abolished by β-adrenoceptor inhibitor, propranolol. In contrast, mesenteric arteries were contracted by NA and propranolol potentiated this contraction. Mesenteric arteries showed a higher expression of α1A adrenoceptors than spinal arteries, while no significant difference was found in other adrenoceptor isoforms.
We found SCBF reduced at MAP below 50 mmHg and that the SCBF increased significantly in MAP range between 50 and 100 mmHg. Elevating MAP above 100 mmHg was not associated with a further increase in SCBF. We also showed that NA increases SCBF in-vivo and relaxes spinal arteries ex-vivo. This effect was associated with a low arterial expression of α adrenoceptors over β adrenoceptors in the spinal cord.
These findings challenge the assumption that SCBF is solely dictated by MAP within autoregulatory limits, emphasizing the necessity of considering noradrenaline-induced vasorelaxation in the spinal arteries of TSCI patients.</description><identifier>ISSN: 1529-9430</identifier><identifier>ISSN: 1878-1632</identifier><identifier>EISSN: 1878-1632</identifier><identifier>DOI: 10.1016/j.spinee.2024.11.010</identifier><identifier>PMID: 39613033</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adrenergic receptors ; Noradrenaline ; Pigs ; Spinal cord blood flow ; Vasodilation ; Vasopressor</subject><ispartof>The spine journal, 2024-11</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1563-72a6a58d8ed233f7dc51857a602726a5d32b4b7771be96dfc87e8f5fbe7c19023</cites><orcidid>0000-0001-5431-4409 ; 0000-0002-3303-1095 ; 0009-0002-4711-4729</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1529943024011513$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39613033$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Entezari, Seyar</creatorcontrib><creatorcontrib>Thygesen, Mathias Møller</creatorcontrib><creatorcontrib>Staehr, Christian</creatorcontrib><creatorcontrib>Melnikova, Elizaveta</creatorcontrib><creatorcontrib>Skov, Mathias</creatorcontrib><creatorcontrib>Rajanathan, Rajkumar</creatorcontrib><creatorcontrib>Rasmussen, Mads</creatorcontrib><creatorcontrib>Rasmussen, Mikkel Mylius</creatorcontrib><creatorcontrib>Matchkov, Vladimir V.</creatorcontrib><title>Spinal cord blood flow elevation with systemic vasopressor noradrenaline is partly mediated by vasodilation of spinal arteries due to reduced expression of alpha adrenoreceptors</title><title>The spine journal</title><addtitle>Spine J</addtitle><description>Elevation of mean arterial blood pressure (MAP) has been proposed to raise spinal cord blood flow (SCBF) after traumatic spinal cord injury (TSCI). Current clinical guidelines for cervical TSCI suggest maintaining MAP 85–90 mmHg for 5–7 days using vasopressors, eg, noradrenaline. However, it remains unknown whether these interventions that promote an increased systemic MAP result in improved perfusion in the spinal cord. The local effect of vasopressors on the spinal cord arteries also remains unknown.
The aim of this study was to investigate whether the increased systemic MAP results in increased SCBF, and secondly, to examine the mechanism behind noradrenaline (NA) action in spinal cord arteries.
An experimental animal study.
The study included nine 38–42 kg landrace pigs. In six pigs, MAP was gradually elevated using NA and continuous SCBF was recorded by laser doppler flowmetry. Spinal cord samples from these 6 pigs were excised for isolation of spinal cord arteries that were used for ex-vivo vascular function assessment in isometric myograph. Segments of mesentery from another 3 pigs were used to dissect mesenteric small arteries that were also studied in myograph, as control peripheral arteries. Other spinal cord and mesenteric arterial segments from the same biopsies were dissected and snap-frozen for the following expression analysis. Adrenoceptor's expression in arteries of all included animals was assessed with quantitative PCR.
The controlled mixed model found that SCBF was lower at MAP below 50 mmHg and that SCBF increased significantly in the MAP range of 50-100 mmHg (p=.02). Further increase of MAP did not significantly affect SCBF (at MAP range of 100–150 mmHg, p=.15; at 150–200 mmHg, p=.51). However, SCBF significantly increased over the study time-course (at 80 min, p=.002; at 100 min, p<.001), which was dependent on the experimental duration being a confounder of increased exposure to large doses of NA. Isolated spinal arteries did not contract to NA ex-vivo and even showed a tendency for vasorelaxation. This relaxation was abolished by β-adrenoceptor inhibitor, propranolol. In contrast, mesenteric arteries were contracted by NA and propranolol potentiated this contraction. Mesenteric arteries showed a higher expression of α1A adrenoceptors than spinal arteries, while no significant difference was found in other adrenoceptor isoforms.
We found SCBF reduced at MAP below 50 mmHg and that the SCBF increased significantly in MAP range between 50 and 100 mmHg. Elevating MAP above 100 mmHg was not associated with a further increase in SCBF. We also showed that NA increases SCBF in-vivo and relaxes spinal arteries ex-vivo. This effect was associated with a low arterial expression of α adrenoceptors over β adrenoceptors in the spinal cord.
These findings challenge the assumption that SCBF is solely dictated by MAP within autoregulatory limits, emphasizing the necessity of considering noradrenaline-induced vasorelaxation in the spinal arteries of TSCI patients.</description><subject>Adrenergic receptors</subject><subject>Noradrenaline</subject><subject>Pigs</subject><subject>Spinal cord blood flow</subject><subject>Vasodilation</subject><subject>Vasopressor</subject><issn>1529-9430</issn><issn>1878-1632</issn><issn>1878-1632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kc2O1DAQhCMEYn_gDRDykUuC207i5IKEVsuPtBIH4Gw5dkfrkScO7mR257F4Q7yTgSMnW_JXVe2uongDvAIO7ftdRbOfECvBRV0BVBz4s-ISOtWV0ErxPN8b0Zd9LflFcUW045x3CsTL4kL2LUgu5WXx-3s2MYHZmBwbQoyOjSE-MAx4MIuPE3vwyz2jIy2495YdDMU5IVFMbIrJuIRZnudgnths0hKObI_OmwWz3_HEOx82qzgy2uIyiMkjMbciWyJL6FabFfh4Mj_DJsz3hp0yYkKL8xITvSpejCYQvj6f18XPT7c_br6Ud98-f735eFdaaFpZKmFa03SuQyekHJWzDXSNMi0XSuQXJ8VQD0opGLBv3Wg7hd3YjAMqCz0X8rp4t_nOKf5akRa992QxBDNhXElLkLWUALLJaL2hNkWihKOek9-bdNTA9VNZeqe3svRTWRpA57Ky7O05YR3yzv6J_raTgQ8bgPmfB49Jk_U45UX5vI5Fu-j_n_AHZrCs8g</recordid><startdate>20241127</startdate><enddate>20241127</enddate><creator>Entezari, Seyar</creator><creator>Thygesen, Mathias Møller</creator><creator>Staehr, Christian</creator><creator>Melnikova, Elizaveta</creator><creator>Skov, Mathias</creator><creator>Rajanathan, Rajkumar</creator><creator>Rasmussen, Mads</creator><creator>Rasmussen, Mikkel Mylius</creator><creator>Matchkov, Vladimir V.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5431-4409</orcidid><orcidid>https://orcid.org/0000-0002-3303-1095</orcidid><orcidid>https://orcid.org/0009-0002-4711-4729</orcidid></search><sort><creationdate>20241127</creationdate><title>Spinal cord blood flow elevation with systemic vasopressor noradrenaline is partly mediated by vasodilation of spinal arteries due to reduced expression of alpha adrenoreceptors</title><author>Entezari, Seyar ; Thygesen, Mathias Møller ; Staehr, Christian ; Melnikova, Elizaveta ; Skov, Mathias ; Rajanathan, Rajkumar ; Rasmussen, Mads ; Rasmussen, Mikkel Mylius ; Matchkov, Vladimir V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1563-72a6a58d8ed233f7dc51857a602726a5d32b4b7771be96dfc87e8f5fbe7c19023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adrenergic receptors</topic><topic>Noradrenaline</topic><topic>Pigs</topic><topic>Spinal cord blood flow</topic><topic>Vasodilation</topic><topic>Vasopressor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Entezari, Seyar</creatorcontrib><creatorcontrib>Thygesen, Mathias Møller</creatorcontrib><creatorcontrib>Staehr, Christian</creatorcontrib><creatorcontrib>Melnikova, Elizaveta</creatorcontrib><creatorcontrib>Skov, Mathias</creatorcontrib><creatorcontrib>Rajanathan, Rajkumar</creatorcontrib><creatorcontrib>Rasmussen, Mads</creatorcontrib><creatorcontrib>Rasmussen, Mikkel Mylius</creatorcontrib><creatorcontrib>Matchkov, Vladimir V.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The spine journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Entezari, Seyar</au><au>Thygesen, Mathias Møller</au><au>Staehr, Christian</au><au>Melnikova, Elizaveta</au><au>Skov, Mathias</au><au>Rajanathan, Rajkumar</au><au>Rasmussen, Mads</au><au>Rasmussen, Mikkel Mylius</au><au>Matchkov, Vladimir V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spinal cord blood flow elevation with systemic vasopressor noradrenaline is partly mediated by vasodilation of spinal arteries due to reduced expression of alpha adrenoreceptors</atitle><jtitle>The spine journal</jtitle><addtitle>Spine J</addtitle><date>2024-11-27</date><risdate>2024</risdate><issn>1529-9430</issn><issn>1878-1632</issn><eissn>1878-1632</eissn><abstract>Elevation of mean arterial blood pressure (MAP) has been proposed to raise spinal cord blood flow (SCBF) after traumatic spinal cord injury (TSCI). Current clinical guidelines for cervical TSCI suggest maintaining MAP 85–90 mmHg for 5–7 days using vasopressors, eg, noradrenaline. However, it remains unknown whether these interventions that promote an increased systemic MAP result in improved perfusion in the spinal cord. The local effect of vasopressors on the spinal cord arteries also remains unknown.
The aim of this study was to investigate whether the increased systemic MAP results in increased SCBF, and secondly, to examine the mechanism behind noradrenaline (NA) action in spinal cord arteries.
An experimental animal study.
The study included nine 38–42 kg landrace pigs. In six pigs, MAP was gradually elevated using NA and continuous SCBF was recorded by laser doppler flowmetry. Spinal cord samples from these 6 pigs were excised for isolation of spinal cord arteries that were used for ex-vivo vascular function assessment in isometric myograph. Segments of mesentery from another 3 pigs were used to dissect mesenteric small arteries that were also studied in myograph, as control peripheral arteries. Other spinal cord and mesenteric arterial segments from the same biopsies were dissected and snap-frozen for the following expression analysis. Adrenoceptor's expression in arteries of all included animals was assessed with quantitative PCR.
The controlled mixed model found that SCBF was lower at MAP below 50 mmHg and that SCBF increased significantly in the MAP range of 50-100 mmHg (p=.02). Further increase of MAP did not significantly affect SCBF (at MAP range of 100–150 mmHg, p=.15; at 150–200 mmHg, p=.51). However, SCBF significantly increased over the study time-course (at 80 min, p=.002; at 100 min, p<.001), which was dependent on the experimental duration being a confounder of increased exposure to large doses of NA. Isolated spinal arteries did not contract to NA ex-vivo and even showed a tendency for vasorelaxation. This relaxation was abolished by β-adrenoceptor inhibitor, propranolol. In contrast, mesenteric arteries were contracted by NA and propranolol potentiated this contraction. Mesenteric arteries showed a higher expression of α1A adrenoceptors than spinal arteries, while no significant difference was found in other adrenoceptor isoforms.
We found SCBF reduced at MAP below 50 mmHg and that the SCBF increased significantly in MAP range between 50 and 100 mmHg. Elevating MAP above 100 mmHg was not associated with a further increase in SCBF. We also showed that NA increases SCBF in-vivo and relaxes spinal arteries ex-vivo. This effect was associated with a low arterial expression of α adrenoceptors over β adrenoceptors in the spinal cord.
These findings challenge the assumption that SCBF is solely dictated by MAP within autoregulatory limits, emphasizing the necessity of considering noradrenaline-induced vasorelaxation in the spinal arteries of TSCI patients.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39613033</pmid><doi>10.1016/j.spinee.2024.11.010</doi><orcidid>https://orcid.org/0000-0001-5431-4409</orcidid><orcidid>https://orcid.org/0000-0002-3303-1095</orcidid><orcidid>https://orcid.org/0009-0002-4711-4729</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adrenergic receptors Noradrenaline Pigs Spinal cord blood flow Vasodilation Vasopressor |
| title | Spinal cord blood flow elevation with systemic vasopressor noradrenaline is partly mediated by vasodilation of spinal arteries due to reduced expression of alpha adrenoreceptors |
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