Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion
We previously showed that brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) is cardioprotective in a canine model of ischemia-reperfusion. This study tested the hypothesis that the early minutes of reperfusion (R) during which postconditioning (Post-con) is...
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| creator | KIN, Hajime ZHAO, Zhi-Qing SUN, He-Ying WANG, Ning-Ping CORVERA, Joel S HALKOS, Michael E KERENDI, Faraz GUYTON, Robert A VINTEN-JOHANSEN, Jakob |
| description | We previously showed that brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) is cardioprotective in a canine model of ischemia-reperfusion. This study tested the hypothesis that the early minutes of reperfusion (R) during which postconditioning (Post-con) is applied are critical to its cardioprotection.
In anesthetized open-chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 h. All rats were randomly divided into six groups: Control (n=8): no intervention at R; Ischemic preconditioning (IPC) (n=8): the LCA was occluded for 5 min followed by 10 min of R before the index occlusion; Post-con 1 (n=8): after LCA occlusion, three cycles of 10 s R followed by 10 s LCA re-occlusion were applied during the first minute of R; Post-con 2 (n=8): Six cycles of 10 s R and 10 s re-occlusion were applied during the first 2 min of R; Delayed Post-con (n=8): the ligature was loosened for full reflow for the first minute of R, after which the three-cycle Post-con algorithm was applied; Sham (n=6): the surgical procedure was identical to other groups, but the LCA ligature was not ligated.
Infarct size (TTC staining) was 23% smaller in Post-con 1 (40+/-2%*) than in Control (52+/-3%), confirmed by plasma creatine kinase activity (18+/-2* vs. 46+/-6 IU/g protein). There was no further reduction in infarct size with 6 cycles of Post-con (40+/-2.9%, p>0.05 vs. Post-con 1). Meanwhile, infarct size reduction was significantly greater in the IPC group (17+/-3%) than in Post-con1 (p |
| doi_str_mv | 10.1016/j.cardiores.2004.01.006 |
| format | Article |
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In anesthetized open-chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 h. All rats were randomly divided into six groups: Control (n=8): no intervention at R; Ischemic preconditioning (IPC) (n=8): the LCA was occluded for 5 min followed by 10 min of R before the index occlusion; Post-con 1 (n=8): after LCA occlusion, three cycles of 10 s R followed by 10 s LCA re-occlusion were applied during the first minute of R; Post-con 2 (n=8): Six cycles of 10 s R and 10 s re-occlusion were applied during the first 2 min of R; Delayed Post-con (n=8): the ligature was loosened for full reflow for the first minute of R, after which the three-cycle Post-con algorithm was applied; Sham (n=6): the surgical procedure was identical to other groups, but the LCA ligature was not ligated.
Infarct size (TTC staining) was 23% smaller in Post-con 1 (40+/-2%*) than in Control (52+/-3%), confirmed by plasma creatine kinase activity (18+/-2* vs. 46+/-6 IU/g protein). There was no further reduction in infarct size with 6 cycles of Post-con (40+/-2.9%, p>0.05 vs. Post-con 1). Meanwhile, infarct size reduction was significantly greater in the IPC group (17+/-3%) than in Post-con1 (p<0.01). The plasma lipid peroxidation product malondialdehyde (MDA, microM/ml) was less after R in IPC and Post-con 1 (0.8+/-0.07* and 0.8+/-0.06*) vs. Control (1.21+/-0.08), consistent with a visual decrease in superoxide anion generation (dihydroethidium staining) in the AAR myocardium after 3 h of reperfusion. Neutrophil accumulation (myeloperoxidase activity, MPO, U/100 g tissue) in the AAR was less in IPC (1.4+/-0.3*) and Post-con 1 (2.5+/-0.3*) vs. Control (5.5+/-0.6). The reductions in infarct size, creatine kinase, MDA and DHE staining were lost with delayed Post-con, while MPO activity remained lower than in Control (3.2+/-0.4*).
(1) Post-con at onset of R reduces myocardial injury; (2) cardioprotection may be mediated, in part, by inhibiting oxidant generation and oxidant mediated injury; (3) the first minute of R in the rat model is critical to cardioprotection by Post-con; and (4) cardioprotection by Post-con may be independent of neutrophil accumulation in AAR. *p<0.05 Post-con vs. Control.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1016/j.cardiores.2004.01.006</identifier><identifier>PMID: 15023554</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Biological and medical sciences ; Cardiology. Vascular system ; Coronary heart disease ; Creatine Kinase - blood ; Heart ; Male ; Malondialdehyde - blood ; Medical sciences ; Myocardial Ischemia - blood ; Myocardial Ischemia - pathology ; Myocardial Reperfusion - methods ; Myocardial Reperfusion Injury - blood ; Myocardial Reperfusion Injury - pathology ; Myocardial Reperfusion Injury - prevention & control ; Myocarditis. Cardiomyopathies ; Myocardium - enzymology ; Myocardium - pathology ; Peroxidase - metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Cardiovascular research, 2004-04, Vol.62 (1), p.74-85</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15590921$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15023554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KIN, Hajime</creatorcontrib><creatorcontrib>ZHAO, Zhi-Qing</creatorcontrib><creatorcontrib>SUN, He-Ying</creatorcontrib><creatorcontrib>WANG, Ning-Ping</creatorcontrib><creatorcontrib>CORVERA, Joel S</creatorcontrib><creatorcontrib>HALKOS, Michael E</creatorcontrib><creatorcontrib>KERENDI, Faraz</creatorcontrib><creatorcontrib>GUYTON, Robert A</creatorcontrib><creatorcontrib>VINTEN-JOHANSEN, Jakob</creatorcontrib><title>Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>We previously showed that brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) is cardioprotective in a canine model of ischemia-reperfusion. This study tested the hypothesis that the early minutes of reperfusion (R) during which postconditioning (Post-con) is applied are critical to its cardioprotection.
In anesthetized open-chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 h. All rats were randomly divided into six groups: Control (n=8): no intervention at R; Ischemic preconditioning (IPC) (n=8): the LCA was occluded for 5 min followed by 10 min of R before the index occlusion; Post-con 1 (n=8): after LCA occlusion, three cycles of 10 s R followed by 10 s LCA re-occlusion were applied during the first minute of R; Post-con 2 (n=8): Six cycles of 10 s R and 10 s re-occlusion were applied during the first 2 min of R; Delayed Post-con (n=8): the ligature was loosened for full reflow for the first minute of R, after which the three-cycle Post-con algorithm was applied; Sham (n=6): the surgical procedure was identical to other groups, but the LCA ligature was not ligated.
Infarct size (TTC staining) was 23% smaller in Post-con 1 (40+/-2%*) than in Control (52+/-3%), confirmed by plasma creatine kinase activity (18+/-2* vs. 46+/-6 IU/g protein). There was no further reduction in infarct size with 6 cycles of Post-con (40+/-2.9%, p>0.05 vs. Post-con 1). Meanwhile, infarct size reduction was significantly greater in the IPC group (17+/-3%) than in Post-con1 (p<0.01). The plasma lipid peroxidation product malondialdehyde (MDA, microM/ml) was less after R in IPC and Post-con 1 (0.8+/-0.07* and 0.8+/-0.06*) vs. Control (1.21+/-0.08), consistent with a visual decrease in superoxide anion generation (dihydroethidium staining) in the AAR myocardium after 3 h of reperfusion. Neutrophil accumulation (myeloperoxidase activity, MPO, U/100 g tissue) in the AAR was less in IPC (1.4+/-0.3*) and Post-con 1 (2.5+/-0.3*) vs. Control (5.5+/-0.6). The reductions in infarct size, creatine kinase, MDA and DHE staining were lost with delayed Post-con, while MPO activity remained lower than in Control (3.2+/-0.4*).
(1) Post-con at onset of R reduces myocardial injury; (2) cardioprotection may be mediated, in part, by inhibiting oxidant generation and oxidant mediated injury; (3) the first minute of R in the rat model is critical to cardioprotection by Post-con; and (4) cardioprotection by Post-con may be independent of neutrophil accumulation in AAR. *p<0.05 Post-con vs. Control.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Coronary heart disease</subject><subject>Creatine Kinase - blood</subject><subject>Heart</subject><subject>Male</subject><subject>Malondialdehyde - blood</subject><subject>Medical sciences</subject><subject>Myocardial Ischemia - blood</subject><subject>Myocardial Ischemia - pathology</subject><subject>Myocardial Reperfusion - methods</subject><subject>Myocardial Reperfusion Injury - blood</subject><subject>Myocardial Reperfusion Injury - pathology</subject><subject>Myocardial Reperfusion Injury - prevention & control</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>Myocardium - enzymology</subject><subject>Myocardium - pathology</subject><subject>Peroxidase - metabolism</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkMtKxDAUhoMozjj6CpqN7lpz7WUpgzcY0IWuS5qeOhnatCapUHx5o47g6lz4_v9cELqgJKWEZte7VCvXmMGBTxkhIiU0JSQ7QEuaS5lwJuQhWhJCiiTjGV-gE-93sZQyF8doQSVhXEqxRJ_Pgw96sI0JZrDGvmEVAthJBfC4n4efMarDxust9EYlDkZw7eQjjY3dTW7G9RyzramjRdTDB9jgYweHLWBQrptxb-z0bTi0-J_-FB21qvNwto8r9Hp3-7J-SDZP94_rm00yMp6HpOaNbJhkWckYIwIYsLg9AdZIDlw0ulA81yCoaFuSN2WhaUZ5LnlRQ6tLwVfo6td3dMP7BD5UfTwHuk5ZGCZf5fFn0TKL4PkenOoemmp0pldurv7eFYHLPaC8Vl3rlNXG_-NkSUpG-Rd7ZX-Z</recordid><startdate>20040401</startdate><enddate>20040401</enddate><creator>KIN, Hajime</creator><creator>ZHAO, Zhi-Qing</creator><creator>SUN, He-Ying</creator><creator>WANG, Ning-Ping</creator><creator>CORVERA, Joel S</creator><creator>HALKOS, Michael E</creator><creator>KERENDI, Faraz</creator><creator>GUYTON, Robert A</creator><creator>VINTEN-JOHANSEN, Jakob</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20040401</creationdate><title>Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion</title><author>KIN, Hajime ; ZHAO, Zhi-Qing ; SUN, He-Ying ; WANG, Ning-Ping ; CORVERA, Joel S ; HALKOS, Michael E ; KERENDI, Faraz ; GUYTON, Robert A ; VINTEN-JOHANSEN, Jakob</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p237t-b3d5d2526922204e2e20230e2d53e34dc8a37ce414ff07d98c16137538befc943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiology. Vascular system</topic><topic>Coronary heart disease</topic><topic>Creatine Kinase - blood</topic><topic>Heart</topic><topic>Male</topic><topic>Malondialdehyde - blood</topic><topic>Medical sciences</topic><topic>Myocardial Ischemia - blood</topic><topic>Myocardial Ischemia - pathology</topic><topic>Myocardial Reperfusion - methods</topic><topic>Myocardial Reperfusion Injury - blood</topic><topic>Myocardial Reperfusion Injury - pathology</topic><topic>Myocardial Reperfusion Injury - prevention & control</topic><topic>Myocarditis. Cardiomyopathies</topic><topic>Myocardium - enzymology</topic><topic>Myocardium - pathology</topic><topic>Peroxidase - metabolism</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KIN, Hajime</creatorcontrib><creatorcontrib>ZHAO, Zhi-Qing</creatorcontrib><creatorcontrib>SUN, He-Ying</creatorcontrib><creatorcontrib>WANG, Ning-Ping</creatorcontrib><creatorcontrib>CORVERA, Joel S</creatorcontrib><creatorcontrib>HALKOS, Michael E</creatorcontrib><creatorcontrib>KERENDI, Faraz</creatorcontrib><creatorcontrib>GUYTON, Robert A</creatorcontrib><creatorcontrib>VINTEN-JOHANSEN, Jakob</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KIN, Hajime</au><au>ZHAO, Zhi-Qing</au><au>SUN, He-Ying</au><au>WANG, Ning-Ping</au><au>CORVERA, Joel S</au><au>HALKOS, Michael E</au><au>KERENDI, Faraz</au><au>GUYTON, Robert A</au><au>VINTEN-JOHANSEN, Jakob</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2004-04-01</date><risdate>2004</risdate><volume>62</volume><issue>1</issue><spage>74</spage><epage>85</epage><pages>74-85</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>We previously showed that brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) is cardioprotective in a canine model of ischemia-reperfusion. This study tested the hypothesis that the early minutes of reperfusion (R) during which postconditioning (Post-con) is applied are critical to its cardioprotection.
In anesthetized open-chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 h. All rats were randomly divided into six groups: Control (n=8): no intervention at R; Ischemic preconditioning (IPC) (n=8): the LCA was occluded for 5 min followed by 10 min of R before the index occlusion; Post-con 1 (n=8): after LCA occlusion, three cycles of 10 s R followed by 10 s LCA re-occlusion were applied during the first minute of R; Post-con 2 (n=8): Six cycles of 10 s R and 10 s re-occlusion were applied during the first 2 min of R; Delayed Post-con (n=8): the ligature was loosened for full reflow for the first minute of R, after which the three-cycle Post-con algorithm was applied; Sham (n=6): the surgical procedure was identical to other groups, but the LCA ligature was not ligated.
Infarct size (TTC staining) was 23% smaller in Post-con 1 (40+/-2%*) than in Control (52+/-3%), confirmed by plasma creatine kinase activity (18+/-2* vs. 46+/-6 IU/g protein). There was no further reduction in infarct size with 6 cycles of Post-con (40+/-2.9%, p>0.05 vs. Post-con 1). Meanwhile, infarct size reduction was significantly greater in the IPC group (17+/-3%) than in Post-con1 (p<0.01). The plasma lipid peroxidation product malondialdehyde (MDA, microM/ml) was less after R in IPC and Post-con 1 (0.8+/-0.07* and 0.8+/-0.06*) vs. Control (1.21+/-0.08), consistent with a visual decrease in superoxide anion generation (dihydroethidium staining) in the AAR myocardium after 3 h of reperfusion. Neutrophil accumulation (myeloperoxidase activity, MPO, U/100 g tissue) in the AAR was less in IPC (1.4+/-0.3*) and Post-con 1 (2.5+/-0.3*) vs. Control (5.5+/-0.6). The reductions in infarct size, creatine kinase, MDA and DHE staining were lost with delayed Post-con, while MPO activity remained lower than in Control (3.2+/-0.4*).
(1) Post-con at onset of R reduces myocardial injury; (2) cardioprotection may be mediated, in part, by inhibiting oxidant generation and oxidant mediated injury; (3) the first minute of R in the rat model is critical to cardioprotection by Post-con; and (4) cardioprotection by Post-con may be independent of neutrophil accumulation in AAR. *p<0.05 Post-con vs. Control.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>15023554</pmid><doi>10.1016/j.cardiores.2004.01.006</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Cardiology. Vascular system Coronary heart disease Creatine Kinase - blood Heart Male Malondialdehyde - blood Medical sciences Myocardial Ischemia - blood Myocardial Ischemia - pathology Myocardial Reperfusion - methods Myocardial Reperfusion Injury - blood Myocardial Reperfusion Injury - pathology Myocardial Reperfusion Injury - prevention & control Myocarditis. Cardiomyopathies Myocardium - enzymology Myocardium - pathology Peroxidase - metabolism Random Allocation Rats Rats, Sprague-Dawley |
| title | Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion |
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