Ischemia-reperfusion injury of the spinal cord: Protective effect of the hydroxyl radical scavenger dimethylthiourea
Purpose: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusio...
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| Veröffentlicht in: | Journal of vascular surgery 1994-09, Vol.20 (3), p.444-450 |
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| creator | Wisselink, Willem Money, Samuel R. Crockett, Donald E. Nguyen, Justine H. Becker, Mark O. Farr, Gist H. Hollier, Larry H. |
| description | Purpose: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both.
Methods: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination.
Results: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (1011) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10).
Conclusions: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits. |
| doi_str_mv | 10.1016/0741-5214(94)90144-9 |
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Methods: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination.
Results: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (1011) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10).
Conclusions: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits.</description><identifier>ISSN: 0741-5214</identifier><identifier>EISSN: 1097-6809</identifier><identifier>DOI: 10.1016/0741-5214(94)90144-9</identifier><identifier>PMID: 8084038</identifier><language>eng</language><publisher>United States: Mosby, Inc</publisher><subject>Animals ; Aorta - surgery ; Arterial Occlusive Diseases - surgery ; Constriction ; Free Radical Scavengers ; Infusions, Intravenous ; Paraplegia - epidemiology ; Paraplegia - etiology ; Paraplegia - prevention & control ; Postoperative Care ; Preoperative Care ; Rabbits ; Random Allocation ; Reperfusion Injury - epidemiology ; Reperfusion Injury - etiology ; Reperfusion Injury - prevention & control ; Spinal Cord Injuries - epidemiology ; Spinal Cord Injuries - etiology ; Spinal Cord Injuries - prevention & control ; Thiourea - administration & dosage ; Thiourea - analogs & derivatives ; Time Factors</subject><ispartof>Journal of vascular surgery, 1994-09, Vol.20 (3), p.444-450</ispartof><rights>1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c403t-4302837323141d99758b4e13c70981073df2d8f58a23edd27c94a5a634e5356e3</citedby><cites>FETCH-LOGICAL-c403t-4302837323141d99758b4e13c70981073df2d8f58a23edd27c94a5a634e5356e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0741-5214(94)90144-9$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8084038$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wisselink, Willem</creatorcontrib><creatorcontrib>Money, Samuel R.</creatorcontrib><creatorcontrib>Crockett, Donald E.</creatorcontrib><creatorcontrib>Nguyen, Justine H.</creatorcontrib><creatorcontrib>Becker, Mark O.</creatorcontrib><creatorcontrib>Farr, Gist H.</creatorcontrib><creatorcontrib>Hollier, Larry H.</creatorcontrib><title>Ischemia-reperfusion injury of the spinal cord: Protective effect of the hydroxyl radical scavenger dimethylthiourea</title><title>Journal of vascular surgery</title><addtitle>J Vasc Surg</addtitle><description>Purpose: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both.
Methods: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination.
Results: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (1011) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10).
Conclusions: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits.</description><subject>Animals</subject><subject>Aorta - surgery</subject><subject>Arterial Occlusive Diseases - surgery</subject><subject>Constriction</subject><subject>Free Radical Scavengers</subject><subject>Infusions, Intravenous</subject><subject>Paraplegia - epidemiology</subject><subject>Paraplegia - etiology</subject><subject>Paraplegia - prevention & control</subject><subject>Postoperative Care</subject><subject>Preoperative Care</subject><subject>Rabbits</subject><subject>Random Allocation</subject><subject>Reperfusion Injury - epidemiology</subject><subject>Reperfusion Injury - etiology</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Spinal Cord Injuries - epidemiology</subject><subject>Spinal Cord Injuries - etiology</subject><subject>Spinal Cord Injuries - prevention & control</subject><subject>Thiourea - administration & dosage</subject><subject>Thiourea - analogs & derivatives</subject><subject>Time Factors</subject><issn>0741-5214</issn><issn>1097-6809</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1r2zAYh8VYydJu_0EHOo324E6yZEvaoVBKPwKB7bCdhSK9rhVsK5PsUP_3tUmaY0Egwe95P_QgdEnJDSW0_EkEp1mRU36l-LUilPNMfUJLSpTISknUZ7Q8IV_QeUpbQigtpFighSSSEyaXqF8lW0PrTRZhB7Eakg8d9t12iCMOFe5rwGnnO9NgG6L7hf_E0IPt_R4wVNX0eqfq0cXwOjY4GuftxCdr9tC9QMTOt9DXY9PXPgwRzFd0VpkmwbfjfYH-PT78vX_O1r-fVvd368xOy_UZZySXTLCcUU6dUqKQGw6UWUGUpEQwV-VOVoU0OQPncmEVN4UpGYeCFSWwC_Tj0HcXw_8BUq9bnyw0jekgDEmLUpCykGoC-QG0MaQUodK76FsTR02JnmXr2aSeTWo1nVm2nsu-H_sPmxbcqehod8pvDzlMn9x7iDpZD50F5-NkTrvgPx7wBvRIjzw</recordid><startdate>19940901</startdate><enddate>19940901</enddate><creator>Wisselink, Willem</creator><creator>Money, Samuel R.</creator><creator>Crockett, Donald E.</creator><creator>Nguyen, Justine H.</creator><creator>Becker, Mark O.</creator><creator>Farr, Gist H.</creator><creator>Hollier, Larry H.</creator><general>Mosby, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19940901</creationdate><title>Ischemia-reperfusion injury of the spinal cord: Protective effect of the hydroxyl radical scavenger dimethylthiourea</title><author>Wisselink, Willem ; Money, Samuel R. ; Crockett, Donald E. ; Nguyen, Justine H. ; Becker, Mark O. ; Farr, Gist H. ; Hollier, Larry H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c403t-4302837323141d99758b4e13c70981073df2d8f58a23edd27c94a5a634e5356e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Aorta - surgery</topic><topic>Arterial Occlusive Diseases - surgery</topic><topic>Constriction</topic><topic>Free Radical Scavengers</topic><topic>Infusions, Intravenous</topic><topic>Paraplegia - epidemiology</topic><topic>Paraplegia - etiology</topic><topic>Paraplegia - prevention & control</topic><topic>Postoperative Care</topic><topic>Preoperative Care</topic><topic>Rabbits</topic><topic>Random Allocation</topic><topic>Reperfusion Injury - epidemiology</topic><topic>Reperfusion Injury - etiology</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Spinal Cord Injuries - epidemiology</topic><topic>Spinal Cord Injuries - etiology</topic><topic>Spinal Cord Injuries - prevention & control</topic><topic>Thiourea - administration & dosage</topic><topic>Thiourea - analogs & derivatives</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wisselink, Willem</creatorcontrib><creatorcontrib>Money, Samuel R.</creatorcontrib><creatorcontrib>Crockett, Donald E.</creatorcontrib><creatorcontrib>Nguyen, Justine H.</creatorcontrib><creatorcontrib>Becker, Mark O.</creatorcontrib><creatorcontrib>Farr, Gist H.</creatorcontrib><creatorcontrib>Hollier, Larry H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of vascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wisselink, Willem</au><au>Money, Samuel R.</au><au>Crockett, Donald E.</au><au>Nguyen, Justine H.</au><au>Becker, Mark O.</au><au>Farr, Gist H.</au><au>Hollier, Larry H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ischemia-reperfusion injury of the spinal cord: Protective effect of the hydroxyl radical scavenger dimethylthiourea</atitle><jtitle>Journal of vascular surgery</jtitle><addtitle>J Vasc Surg</addtitle><date>1994-09-01</date><risdate>1994</risdate><volume>20</volume><issue>3</issue><spage>444</spage><epage>450</epage><pages>444-450</pages><issn>0741-5214</issn><eissn>1097-6809</eissn><abstract>Purpose: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both.
Methods: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination.
Results: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (1011) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10).
Conclusions: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits.</abstract><cop>United States</cop><pub>Mosby, Inc</pub><pmid>8084038</pmid><doi>10.1016/0741-5214(94)90144-9</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0741-5214 |
| ispartof | Journal of vascular surgery, 1994-09, Vol.20 (3), p.444-450 |
| issn | 0741-5214 1097-6809 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; EZB Electronic Journals Library |
| subjects | Animals Aorta - surgery Arterial Occlusive Diseases - surgery Constriction Free Radical Scavengers Infusions, Intravenous Paraplegia - epidemiology Paraplegia - etiology Paraplegia - prevention & control Postoperative Care Preoperative Care Rabbits Random Allocation Reperfusion Injury - epidemiology Reperfusion Injury - etiology Reperfusion Injury - prevention & control Spinal Cord Injuries - epidemiology Spinal Cord Injuries - etiology Spinal Cord Injuries - prevention & control Thiourea - administration & dosage Thiourea - analogs & derivatives Time Factors |
| title | Ischemia-reperfusion injury of the spinal cord: Protective effect of the hydroxyl radical scavenger dimethylthiourea |
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