Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus
Objectives: Calcineurin inhibitors reduce experimental reperfusion injury in the liver, brain, heart, kidney, and small bowel. These studies were undertaken to determine whether these agents are similarly protective against lung ischemia-reperfusion injury. Methods: Left lungs of male rats were rend...
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| creator | Krishnadasan, B. Naidu, B. Rosengart, M. Farr, A.L. Barnes, A. Verrier, E.D. Mulligan, M.S. |
| description | Objectives: Calcineurin inhibitors reduce experimental reperfusion injury in the liver, brain, heart, kidney, and small bowel. These studies were undertaken to determine whether these agents are similarly protective against lung ischemia-reperfusion injury. Methods: Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for as long as 4 hours. Treated animals received cyclosporine A (INN: ciclosporin; 1 or 5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before ischemia, at reperfusion, or 2 hours after reperfusion. Injury was quantitated in terms of tissue polymorphonuclear leukocyte accumulation (myeloperoxidase content), vascular permeability (iodine 125-labeled bovine serum albumin extravasation), and bronchoalveolar lavage leukocyte content. Separate tissue samples were processed for nuclear protein and cytokine messenger RNA. Results: Treatment with cyclosporine (5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before reperfusion reduced lung vascular permeability by 54% and 56% relative to control animals (P |
| doi_str_mv | 10.1067/mtc.2002.120351 |
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J Thorac Cardiovasc Surg 2002;123:756-67</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1067/mtc.2002.120351</identifier><identifier>PMID: 11986604</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Bronchoalveolar Lavage Fluid - cytology ; Capillary Permeability - drug effects ; Cyclosporine - administration & dosage ; Cyclosporine - pharmacokinetics ; Cytokines - biosynthesis ; Cytokines - drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Electrophoretic Mobility Shift Assay ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - pharmacokinetics ; Leukocytes - drug effects ; Lung - blood supply ; Male ; NF-kappa B - biosynthesis ; NF-kappa B - drug effects ; Peroxidase - drug effects ; Preoperative Care ; Rats ; Rats, Long-Evans ; Reperfusion Injury - prevention & control ; RNA, Messenger - biosynthesis ; RNA, Messenger - drug effects ; Tacrolimus - administration & dosage ; Tacrolimus - pharmacokinetics ; Treatment Outcome</subject><ispartof>The Journal of thoracic and cardiovascular surgery, 2002-04, Vol.123 (4), p.756-767</ispartof><rights>2002 American Association for Thoracic Surgery</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-59f5f1652f96e7b5f99cc0e8694ba49839b7e413e4bc82d7be1e7115dc4038193</citedby><cites>FETCH-LOGICAL-c416t-59f5f1652f96e7b5f99cc0e8694ba49839b7e413e4bc82d7be1e7115dc4038193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S002252230205198X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11986604$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krishnadasan, B.</creatorcontrib><creatorcontrib>Naidu, B.</creatorcontrib><creatorcontrib>Rosengart, M.</creatorcontrib><creatorcontrib>Farr, A.L.</creatorcontrib><creatorcontrib>Barnes, A.</creatorcontrib><creatorcontrib>Verrier, E.D.</creatorcontrib><creatorcontrib>Mulligan, M.S.</creatorcontrib><title>Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus</title><title>The Journal of thoracic and cardiovascular surgery</title><addtitle>J Thorac Cardiovasc Surg</addtitle><description>Objectives: Calcineurin inhibitors reduce experimental reperfusion injury in the liver, brain, heart, kidney, and small bowel. These studies were undertaken to determine whether these agents are similarly protective against lung ischemia-reperfusion injury. Methods: Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for as long as 4 hours. Treated animals received cyclosporine A (INN: ciclosporin; 1 or 5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before ischemia, at reperfusion, or 2 hours after reperfusion. Injury was quantitated in terms of tissue polymorphonuclear leukocyte accumulation (myeloperoxidase content), vascular permeability (iodine 125-labeled bovine serum albumin extravasation), and bronchoalveolar lavage leukocyte content. Separate tissue samples were processed for nuclear protein and cytokine messenger RNA. Results: Treatment with cyclosporine (5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before reperfusion reduced lung vascular permeability by 54% and 56% relative to control animals (P <.03). The protective effects of cyclosporine and tacrolimus treatment before reperfusion correlated with 42% and 43% reductions in tissue polymorphonuclear leukocyte (myeloperoxidase) content (P <.008) and marked reductions in bronchoalveolar lavage leukocyte accumulation (P <.01). Administration of cyclosporine or tacrolimus at the time of reperfusion or 2 hours into the reperfusion period offered little or no protection. Animals treated before reperfusion also demonstrated marked reductions in nuclear factor κB activation and expression of proinflammatory cytokine messenger RNA. Conclusion: Cyclosporine and tacrolimus treatment before reperfusion was protective against lung ischemia-reperfusion injury in rats. The mechanism of these protective effects may involve the inhibition of nuclear factor κB, a central transcription factor mediating inflammatory injury. The decreased expression of cytokine messenger RNA indicates that both cyclosporine and tacrolimus may exert their protective effects at the pretranscriptional level.
J Thorac Cardiovasc Surg 2002;123:756-67</description><subject>Animals</subject><subject>Bronchoalveolar Lavage Fluid - cytology</subject><subject>Capillary Permeability - drug effects</subject><subject>Cyclosporine - administration & dosage</subject><subject>Cyclosporine - pharmacokinetics</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - drug effects</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Leukocytes - drug effects</subject><subject>Lung - blood supply</subject><subject>Male</subject><subject>NF-kappa B - biosynthesis</subject><subject>NF-kappa B - drug effects</subject><subject>Peroxidase - drug effects</subject><subject>Preoperative Care</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Reperfusion Injury - prevention & control</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - drug effects</subject><subject>Tacrolimus - administration & dosage</subject><subject>Tacrolimus - pharmacokinetics</subject><subject>Treatment Outcome</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1v1DAURS0EotPCmh3yClaZ2o4_4iVqgSJVYgMSO8txnjseJXGwnaL593iUkVixerLeuVfPB6F3lOwpkep2Km7PCGF7ykgr6Au0o0SrRnbi10u0qwvWCMbaK3Sd85EQogjVr9EVpbqTkvAdyvfgEtgMAx7X-QmH7A4wBdskWCD5NYc44zAf13SqAydbMra-QMJLglgRW8IzYDtMYQ65nJ81ED12JzfGvMQU5rqeB1ysS3EM05rfoFfejhneXuYN-vnl84-7h-bx-9dvd58eG8epLI3QXngqBfNaguqF19o5Ap3UvLdcd63uFXDaAu9dxwbVAwVFqRgcJ21HdXuDPmy9S4q_V8jFTPV7MI52hrhmo87lneYVvN3AemHOCbxZUphsOhlKzNmzqZ7N2bPZPNfE-0v12k8w_OMvYivwcQMO4enwJyQwebLjWHFqjsVlylrDjRKyknojoap4DpBMdgFmB0NNuWKGGP57xl_8vZya</recordid><startdate>20020401</startdate><enddate>20020401</enddate><creator>Krishnadasan, B.</creator><creator>Naidu, B.</creator><creator>Rosengart, M.</creator><creator>Farr, A.L.</creator><creator>Barnes, A.</creator><creator>Verrier, E.D.</creator><creator>Mulligan, M.S.</creator><general>Elsevier Inc</general><general>AATS/WTSA</general><scope>6I.</scope><scope>AAFTH</scope><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>20020401</creationdate><title>Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus</title><author>Krishnadasan, B. ; Naidu, B. ; Rosengart, M. ; Farr, A.L. ; Barnes, A. ; Verrier, E.D. ; Mulligan, M.S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-59f5f1652f96e7b5f99cc0e8694ba49839b7e413e4bc82d7be1e7115dc4038193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Bronchoalveolar Lavage Fluid - cytology</topic><topic>Capillary Permeability - drug effects</topic><topic>Cyclosporine - administration & dosage</topic><topic>Cyclosporine - pharmacokinetics</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - drug effects</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electrophoretic Mobility Shift Assay</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Leukocytes - drug effects</topic><topic>Lung - blood supply</topic><topic>Male</topic><topic>NF-kappa B - biosynthesis</topic><topic>NF-kappa B - drug effects</topic><topic>Peroxidase - drug effects</topic><topic>Preoperative Care</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Reperfusion Injury - prevention & control</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - drug effects</topic><topic>Tacrolimus - administration & dosage</topic><topic>Tacrolimus - pharmacokinetics</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krishnadasan, B.</creatorcontrib><creatorcontrib>Naidu, B.</creatorcontrib><creatorcontrib>Rosengart, M.</creatorcontrib><creatorcontrib>Farr, A.L.</creatorcontrib><creatorcontrib>Barnes, A.</creatorcontrib><creatorcontrib>Verrier, E.D.</creatorcontrib><creatorcontrib>Mulligan, M.S.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>The Journal of thoracic and cardiovascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krishnadasan, B.</au><au>Naidu, B.</au><au>Rosengart, M.</au><au>Farr, A.L.</au><au>Barnes, A.</au><au>Verrier, E.D.</au><au>Mulligan, M.S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2002-04-01</date><risdate>2002</risdate><volume>123</volume><issue>4</issue><spage>756</spage><epage>767</epage><pages>756-767</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><abstract>Objectives: Calcineurin inhibitors reduce experimental reperfusion injury in the liver, brain, heart, kidney, and small bowel. These studies were undertaken to determine whether these agents are similarly protective against lung ischemia-reperfusion injury. Methods: Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for as long as 4 hours. Treated animals received cyclosporine A (INN: ciclosporin; 1 or 5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before ischemia, at reperfusion, or 2 hours after reperfusion. Injury was quantitated in terms of tissue polymorphonuclear leukocyte accumulation (myeloperoxidase content), vascular permeability (iodine 125-labeled bovine serum albumin extravasation), and bronchoalveolar lavage leukocyte content. Separate tissue samples were processed for nuclear protein and cytokine messenger RNA. Results: Treatment with cyclosporine (5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before reperfusion reduced lung vascular permeability by 54% and 56% relative to control animals (P <.03). The protective effects of cyclosporine and tacrolimus treatment before reperfusion correlated with 42% and 43% reductions in tissue polymorphonuclear leukocyte (myeloperoxidase) content (P <.008) and marked reductions in bronchoalveolar lavage leukocyte accumulation (P <.01). Administration of cyclosporine or tacrolimus at the time of reperfusion or 2 hours into the reperfusion period offered little or no protection. Animals treated before reperfusion also demonstrated marked reductions in nuclear factor κB activation and expression of proinflammatory cytokine messenger RNA. Conclusion: Cyclosporine and tacrolimus treatment before reperfusion was protective against lung ischemia-reperfusion injury in rats. The mechanism of these protective effects may involve the inhibition of nuclear factor κB, a central transcription factor mediating inflammatory injury. The decreased expression of cytokine messenger RNA indicates that both cyclosporine and tacrolimus may exert their protective effects at the pretranscriptional level.
J Thorac Cardiovasc Surg 2002;123:756-67</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11986604</pmid><doi>10.1067/mtc.2002.120351</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bronchoalveolar Lavage Fluid - cytology Capillary Permeability - drug effects Cyclosporine - administration & dosage Cyclosporine - pharmacokinetics Cytokines - biosynthesis Cytokines - drug effects Disease Models, Animal Dose-Response Relationship, Drug Electrophoretic Mobility Shift Assay Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - pharmacokinetics Leukocytes - drug effects Lung - blood supply Male NF-kappa B - biosynthesis NF-kappa B - drug effects Peroxidase - drug effects Preoperative Care Rats Rats, Long-Evans Reperfusion Injury - prevention & control RNA, Messenger - biosynthesis RNA, Messenger - drug effects Tacrolimus - administration & dosage Tacrolimus - pharmacokinetics Treatment Outcome |
| title | Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus |
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