Myocardial protection by ischemic preconditioning and δ-opioid receptor activation in the isolated working rat heart
Objective: δ-Opioid receptors are involved in the cardioprotective effect of ischemic preconditioning. This study was designed (1) to assess the protective capacities of ischemic preconditioning and the synthetic δ-opioid receptor agonist D-Ala2-D-Leu5 enkephalin (DADLE) in a functionally oriented e...
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| Veröffentlicht in: | The Journal of thoracic and cardiovascular surgery 2001-11, Vol.122 (5), p.986-992 |
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| creator | Karck, Matthias Tanaka, Satonori Bolling, Steven F. Simon, Andre Su, Tsung-Ping Oeltgen, Peter R. Haverich, Axel |
| description | Objective: δ-Opioid receptors are involved in the cardioprotective effect of ischemic preconditioning. This study was designed (1) to assess the protective capacities of ischemic preconditioning and the synthetic δ-opioid receptor agonist D-Ala2-D-Leu5 enkephalin (DADLE) in a functionally oriented experimental model of ischemia and reperfusion and (2) to assess whether the effects of both protective measures are similarly blocked by naloxone, a nonspecific δ-opioid receptor antagonist. Methods: Sixty-four isolated working rat hearts were subjected to 45 minutes of hypothermic ischemia at 30°C followed by 25 minutes of normothermic reperfusion. Rats were pretreated with DADLE (1 mg/kg body weight intravenously), naloxone (3 mg/kg body weight intravenously), or a combination thereof within 60 minutes before onset of isolated heart perfusion. During the preischemic perfusion period, 8 hearts per group were preconditioned by one cycle of 5 minutes of normothermic global ischemia and subsequent reperfusion whereas another 8 served as nonpreconditioned controls. The postischemic functional recovery of hearts and their creatine kinase leakage were determined. Results: Pretreatment with DADLE and ischemic preconditioning improved the postischemic recovery of aortic flow when compared with nonpreconditioning (57.7% ± 4.0% and 60.8% ± 4.3% vs 40.0% ± 4.2% of preischemic baseline value, P ||.001). Combined pretreatment with DADLE before ischemic preconditioning afforded additional aortic flow recovery compared with pretreatment with DADLE alone (68.6% ± 3.3% vs 57.7% ± 4.0% of preischemic baseline value; P =.038). With combined pretreatment, early postischemic creatine kinase release was lower than control in hearts without pretreatment (0.48 ± 0.11 vs 0.80 ± 0.12 IU/5 minutes per heart; P =.001). Naloxone abolished the beneficial functional effects of pretreatment with DADLE and ischemic preconditioning. Conclusions: Pharmacologic activation of δ-opioid receptors affords improvement of functional protection in isolated working rat hearts similar to that conferred by classic ischemic preconditioning. The combination of both pretreatments reduces ischemic cellular damage and further adds to postischemic functional recovery. These changes are reversed by naloxone, an observation providing evidence that ischemic preconditioning involves signaling through opioid receptors.
J Thorac Cardiovasc Surg 2001;122:986-92 |
| doi_str_mv | 10.1067/mtc.2001.116950 |
| format | Article |
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J Thorac Cardiovasc Surg 2001;122:986-92</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1067/mtc.2001.116950</identifier><identifier>PMID: 11689805</identifier><identifier>CODEN: JTCSAQ</identifier><language>eng</language><publisher>Philadelphia, PA: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Cardiovascular system ; Enkephalin, Leucine-2-Alanine - pharmacology ; Ischemic Preconditioning, Myocardial ; Male ; Medical sciences ; Miscellaneous ; Myocardial Reperfusion Injury - prevention & control ; Naloxone - pharmacology ; Narcotic Antagonists - pharmacology ; Pharmacology. Drug treatments ; Rats ; Rats, Wistar ; Receptors, Opioid, delta - antagonists & inhibitors ; Receptors, Opioid, delta - drug effects ; Receptors, Opioid, delta - physiology</subject><ispartof>The Journal of thoracic and cardiovascular surgery, 2001-11, Vol.122 (5), p.986-992</ispartof><rights>2001 American Association for Thoracic Surgery</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-f9d7febedce0902508478688762540b496c47f3595635675f91b669cb68950423</citedby><cites>FETCH-LOGICAL-c414t-f9d7febedce0902508478688762540b496c47f3595635675f91b669cb68950423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1067/mtc.2001.116950$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14103307$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11689805$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karck, Matthias</creatorcontrib><creatorcontrib>Tanaka, Satonori</creatorcontrib><creatorcontrib>Bolling, Steven F.</creatorcontrib><creatorcontrib>Simon, Andre</creatorcontrib><creatorcontrib>Su, Tsung-Ping</creatorcontrib><creatorcontrib>Oeltgen, Peter R.</creatorcontrib><creatorcontrib>Haverich, Axel</creatorcontrib><title>Myocardial protection by ischemic preconditioning and δ-opioid receptor activation in the isolated working rat heart</title><title>The Journal of thoracic and cardiovascular surgery</title><addtitle>J Thorac Cardiovasc Surg</addtitle><description>Objective: δ-Opioid receptors are involved in the cardioprotective effect of ischemic preconditioning. This study was designed (1) to assess the protective capacities of ischemic preconditioning and the synthetic δ-opioid receptor agonist D-Ala2-D-Leu5 enkephalin (DADLE) in a functionally oriented experimental model of ischemia and reperfusion and (2) to assess whether the effects of both protective measures are similarly blocked by naloxone, a nonspecific δ-opioid receptor antagonist. Methods: Sixty-four isolated working rat hearts were subjected to 45 minutes of hypothermic ischemia at 30°C followed by 25 minutes of normothermic reperfusion. Rats were pretreated with DADLE (1 mg/kg body weight intravenously), naloxone (3 mg/kg body weight intravenously), or a combination thereof within 60 minutes before onset of isolated heart perfusion. During the preischemic perfusion period, 8 hearts per group were preconditioned by one cycle of 5 minutes of normothermic global ischemia and subsequent reperfusion whereas another 8 served as nonpreconditioned controls. The postischemic functional recovery of hearts and their creatine kinase leakage were determined. Results: Pretreatment with DADLE and ischemic preconditioning improved the postischemic recovery of aortic flow when compared with nonpreconditioning (57.7% ± 4.0% and 60.8% ± 4.3% vs 40.0% ± 4.2% of preischemic baseline value, P ||.001). Combined pretreatment with DADLE before ischemic preconditioning afforded additional aortic flow recovery compared with pretreatment with DADLE alone (68.6% ± 3.3% vs 57.7% ± 4.0% of preischemic baseline value; P =.038). With combined pretreatment, early postischemic creatine kinase release was lower than control in hearts without pretreatment (0.48 ± 0.11 vs 0.80 ± 0.12 IU/5 minutes per heart; P =.001). Naloxone abolished the beneficial functional effects of pretreatment with DADLE and ischemic preconditioning. Conclusions: Pharmacologic activation of δ-opioid receptors affords improvement of functional protection in isolated working rat hearts similar to that conferred by classic ischemic preconditioning. The combination of both pretreatments reduces ischemic cellular damage and further adds to postischemic functional recovery. These changes are reversed by naloxone, an observation providing evidence that ischemic preconditioning involves signaling through opioid receptors.
J Thorac Cardiovasc Surg 2001;122:986-92</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Enkephalin, Leucine-2-Alanine - pharmacology</subject><subject>Ischemic Preconditioning, Myocardial</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Myocardial Reperfusion Injury - prevention & control</subject><subject>Naloxone - pharmacology</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Opioid, delta - antagonists & inhibitors</subject><subject>Receptors, Opioid, delta - drug effects</subject><subject>Receptors, Opioid, delta - physiology</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLFuFDEQhi0EIpdATYfckG4vY-_aXpcogoAUlAYkOstrz3KG3fVh-4LuvfIcPBO-3EmpqCzNfP8vz0fIGwZrBlJdzcWtOQBbMya1gGdkxUCrRvbi-3OyAuC8EZy3Z-Q8558AoIDpl-Ss0r3uQazI7ss-Opt8sBPdpljQlRAXOuxpyG6Dc3B1jC4uPhwWYflB7eLp34cmbkMMntYlbktM1NbkvX1Mh4WWDdaGONmCnv6J6dchmWyhG7SpvCIvRjtlfH16L8i3jx--Xn9qbu9uPl-_v21cx7rSjNqrEQf0DkEDF9B3qpd9ryQXHQydlq5TYyu0kK2QSoyaDVJqN9TrBHS8vSCXx9562u8d5mLmehZOk10w7rJRvBbV2gpeHUGXYs4JR7NNYbZpbxiYg2lTTZuDaXM0XRNvT9W7YUb_xJ_UVuDdCbDZ2WlMdnEhP3Edg7YFVTl95LCKuA-YTHYBF4c-VLfF-Bj--4l_ZWubjg</recordid><startdate>20011101</startdate><enddate>20011101</enddate><creator>Karck, Matthias</creator><creator>Tanaka, Satonori</creator><creator>Bolling, Steven F.</creator><creator>Simon, Andre</creator><creator>Su, Tsung-Ping</creator><creator>Oeltgen, Peter R.</creator><creator>Haverich, Axel</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>20011101</creationdate><title>Myocardial protection by ischemic preconditioning and δ-opioid receptor activation in the isolated working rat heart</title><author>Karck, Matthias ; Tanaka, Satonori ; Bolling, Steven F. ; Simon, Andre ; Su, Tsung-Ping ; Oeltgen, Peter R. ; Haverich, Axel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-f9d7febedce0902508478688762540b496c47f3595635675f91b669cb68950423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Enkephalin, Leucine-2-Alanine - pharmacology</topic><topic>Ischemic Preconditioning, Myocardial</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Myocardial Reperfusion Injury - prevention & control</topic><topic>Naloxone - pharmacology</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Opioid, delta - antagonists & inhibitors</topic><topic>Receptors, Opioid, delta - drug effects</topic><topic>Receptors, Opioid, delta - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karck, Matthias</creatorcontrib><creatorcontrib>Tanaka, Satonori</creatorcontrib><creatorcontrib>Bolling, Steven F.</creatorcontrib><creatorcontrib>Simon, Andre</creatorcontrib><creatorcontrib>Su, Tsung-Ping</creatorcontrib><creatorcontrib>Oeltgen, Peter R.</creatorcontrib><creatorcontrib>Haverich, Axel</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</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>Karck, Matthias</au><au>Tanaka, Satonori</au><au>Bolling, Steven F.</au><au>Simon, Andre</au><au>Su, Tsung-Ping</au><au>Oeltgen, Peter R.</au><au>Haverich, Axel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Myocardial protection by ischemic preconditioning and δ-opioid receptor activation in the isolated working rat heart</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2001-11-01</date><risdate>2001</risdate><volume>122</volume><issue>5</issue><spage>986</spage><epage>992</epage><pages>986-992</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><coden>JTCSAQ</coden><abstract>Objective: δ-Opioid receptors are involved in the cardioprotective effect of ischemic preconditioning. This study was designed (1) to assess the protective capacities of ischemic preconditioning and the synthetic δ-opioid receptor agonist D-Ala2-D-Leu5 enkephalin (DADLE) in a functionally oriented experimental model of ischemia and reperfusion and (2) to assess whether the effects of both protective measures are similarly blocked by naloxone, a nonspecific δ-opioid receptor antagonist. Methods: Sixty-four isolated working rat hearts were subjected to 45 minutes of hypothermic ischemia at 30°C followed by 25 minutes of normothermic reperfusion. Rats were pretreated with DADLE (1 mg/kg body weight intravenously), naloxone (3 mg/kg body weight intravenously), or a combination thereof within 60 minutes before onset of isolated heart perfusion. During the preischemic perfusion period, 8 hearts per group were preconditioned by one cycle of 5 minutes of normothermic global ischemia and subsequent reperfusion whereas another 8 served as nonpreconditioned controls. The postischemic functional recovery of hearts and their creatine kinase leakage were determined. Results: Pretreatment with DADLE and ischemic preconditioning improved the postischemic recovery of aortic flow when compared with nonpreconditioning (57.7% ± 4.0% and 60.8% ± 4.3% vs 40.0% ± 4.2% of preischemic baseline value, P ||.001). Combined pretreatment with DADLE before ischemic preconditioning afforded additional aortic flow recovery compared with pretreatment with DADLE alone (68.6% ± 3.3% vs 57.7% ± 4.0% of preischemic baseline value; P =.038). With combined pretreatment, early postischemic creatine kinase release was lower than control in hearts without pretreatment (0.48 ± 0.11 vs 0.80 ± 0.12 IU/5 minutes per heart; P =.001). Naloxone abolished the beneficial functional effects of pretreatment with DADLE and ischemic preconditioning. Conclusions: Pharmacologic activation of δ-opioid receptors affords improvement of functional protection in isolated working rat hearts similar to that conferred by classic ischemic preconditioning. The combination of both pretreatments reduces ischemic cellular damage and further adds to postischemic functional recovery. These changes are reversed by naloxone, an observation providing evidence that ischemic preconditioning involves signaling through opioid receptors.
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| subjects | Animals Biological and medical sciences Cardiovascular system Enkephalin, Leucine-2-Alanine - pharmacology Ischemic Preconditioning, Myocardial Male Medical sciences Miscellaneous Myocardial Reperfusion Injury - prevention & control Naloxone - pharmacology Narcotic Antagonists - pharmacology Pharmacology. Drug treatments Rats Rats, Wistar Receptors, Opioid, delta - antagonists & inhibitors Receptors, Opioid, delta - drug effects Receptors, Opioid, delta - physiology |
| title | Myocardial protection by ischemic preconditioning and δ-opioid receptor activation in the isolated working rat heart |
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