Increased myocardial gene expression of tumor necrosis factor-α and nitric oxide synthase-2: A potential mechanism for depressed myocardial function in hibernating myocardium in humans
Whether cardioinhibitory cytokines are elevated in regions of hibernating myocardium and account in part for the depression in resting function is currently not known. Methods and Results- Thirteen patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperat...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2002-04, Vol.105 (13), p.1537-1540 |
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| creator | KALRA, Dinesh K XI ZHU RAMCHANDANI, Mahesh K LAWRIE, Gerald REARDON, Michael J LEE-JACKSON, Dorellyn WINTERS, William L SIVASUBRAMANIAN, Natarajan MANN, Douglas L ZOGHBI, William A |
| description | Whether cardioinhibitory cytokines are elevated in regions of hibernating myocardium and account in part for the depression in resting function is currently not known. Methods and Results- Thirteen patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperative dobutamine echocardiography (DE) and intraoperative myocardial biopsies. The numbers of copies of mRNA for the negatively inotropic cytokines tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (NOS2) were quantified by reverse transcription-polymerase chain reaction. In normal segments, myocardial TNF-alpha was barely detectable (1.2+/-0.4 copies per 10(6) copies of beta-actin). A 13.7-fold increase in myocardial TNF-alpha was observed in dysfunctional segments with a biphasic response to DE (contractile reserve and ischemia) and was highest (45.5-fold) in segments with ischemia and without contractile reserve (P |
| doi_str_mv | 10.1161/01.CIR.0000013846.72805.7E |
| format | Article |
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TNF-alpha and NOS2 gene expression is regionally upregulated in hibernating myocardium to a level intermediate between that of normal regions and ischemic regions without contractile reserve. This, along with a decline in serum cytokine levels after revascularization proportional to the extent of myocardial viability, suggests a contributing role for cardioinhibitory cytokines in the observed depression of function seen in hibernating myocardium.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.0000013846.72805.7E</identifier><identifier>PMID: 11927517</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Biological and medical sciences ; Cardiology. Vascular system ; Coronary heart disease ; Female ; Heart ; Heart - physiopathology ; Humans ; Male ; Medical sciences ; Middle Aged ; Myocardial Stunning - diagnostic imaging ; Myocardial Stunning - metabolism ; Myocardial Stunning - physiopathology ; Myocardium - metabolism ; Nitric Oxide Synthase - biosynthesis ; Nitric Oxide Synthase - genetics ; Nitric Oxide Synthase Type II ; Nitrites - blood ; Receptors, Adrenergic, beta - metabolism ; RNA, Messenger - biosynthesis ; Transcriptional Activation ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor Necrosis Factor-alpha - genetics ; Ultrasonography ; Ventricular Dysfunction, Left - metabolism ; Ventricular Dysfunction, Left - physiopathology</subject><ispartof>Circulation (New York, N.Y.), 2002-04, Vol.105 (13), p.1537-1540</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c203t-fdb568f6597455d22662fa43fb72ecb6e918c7a03014c411795f4fd6ea400d613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13603375$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11927517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KALRA, Dinesh K</creatorcontrib><creatorcontrib>XI ZHU</creatorcontrib><creatorcontrib>RAMCHANDANI, Mahesh K</creatorcontrib><creatorcontrib>LAWRIE, Gerald</creatorcontrib><creatorcontrib>REARDON, Michael J</creatorcontrib><creatorcontrib>LEE-JACKSON, Dorellyn</creatorcontrib><creatorcontrib>WINTERS, William L</creatorcontrib><creatorcontrib>SIVASUBRAMANIAN, Natarajan</creatorcontrib><creatorcontrib>MANN, Douglas L</creatorcontrib><creatorcontrib>ZOGHBI, William A</creatorcontrib><title>Increased myocardial gene expression of tumor necrosis factor-α and nitric oxide synthase-2: A potential mechanism for depressed myocardial function in hibernating myocardium in humans</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Whether cardioinhibitory cytokines are elevated in regions of hibernating myocardium and account in part for the depression in resting function is currently not known. Methods and Results- Thirteen patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperative dobutamine echocardiography (DE) and intraoperative myocardial biopsies. The numbers of copies of mRNA for the negatively inotropic cytokines tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (NOS2) were quantified by reverse transcription-polymerase chain reaction. In normal segments, myocardial TNF-alpha was barely detectable (1.2+/-0.4 copies per 10(6) copies of beta-actin). A 13.7-fold increase in myocardial TNF-alpha was observed in dysfunctional segments with a biphasic response to DE (contractile reserve and ischemia) and was highest (45.5-fold) in segments with ischemia and without contractile reserve (P<0.001). A similar graded increase was seen for NOS2. Cytokine results were also similar if analysis was performed using recovery of function at 3 months as the index of viability. The change in serum TNF-alpha and nitrite levels from baseline to 3 months after surgery correlated inversely with both the change in ejection fraction and the number of DE viable segments (r=-0.92 to -0.93; P<0.001).
TNF-alpha and NOS2 gene expression is regionally upregulated in hibernating myocardium to a level intermediate between that of normal regions and ischemic regions without contractile reserve. This, along with a decline in serum cytokine levels after revascularization proportional to the extent of myocardial viability, suggests a contributing role for cardioinhibitory cytokines in the observed depression of function seen in hibernating myocardium.</description><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Coronary heart disease</subject><subject>Female</subject><subject>Heart</subject><subject>Heart - physiopathology</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Myocardial Stunning - diagnostic imaging</subject><subject>Myocardial Stunning - metabolism</subject><subject>Myocardial Stunning - physiopathology</subject><subject>Myocardium - metabolism</subject><subject>Nitric Oxide Synthase - biosynthesis</subject><subject>Nitric Oxide Synthase - genetics</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Nitrites - blood</subject><subject>Receptors, Adrenergic, beta - metabolism</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Transcriptional Activation</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Ultrasonography</subject><subject>Ventricular Dysfunction, Left - metabolism</subject><subject>Ventricular Dysfunction, Left - physiopathology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkd2K1DAYhoMo7rh6CxIEPWvNT5NM92wZRh1YEESPQ5p82Ym0yZi0sHNZe-hNeE22s4ODOQnhe773hTwIvaOkplTSj4TWm923miyH8nUja8XWRNRq-wytqGBN1QjePkered5WijN2hV6V8nN-Sq7ES3RFacuUoGqFfu-izWAKODwckzXZBdPje4iA4eGQoZSQIk4ej9OQMo5gcyqhYG_smHL15xGb6HAMYw4Wp4fgAJdjHPdzYsVu8C0-pBHiuIQOYPcmhjJgPyc5OKX_3-unaMelMES8Dx3kaMYQ7_8h03CaTIOJ5TV64U1f4M35vkY_Pm2_b75Ud18_7za3d5VlhI-Vd52Qay9FqxohHGNSMm8a7jvFwHYSWrq2yhBOaGMbSlUrfOOdBNMQ4iTl1-jDU-4hp18TlFEPoVjoexMhTUUrKgSnvJnBmydw-aKSwetDDoPJR02JXsRpQvUsTl_E6ZM4rbbz8ttzy9QN4C6rZ1Mz8P4MmGJN77OJNpQLxyXhs1z-F4mKpsE</recordid><startdate>20020402</startdate><enddate>20020402</enddate><creator>KALRA, Dinesh K</creator><creator>XI ZHU</creator><creator>RAMCHANDANI, Mahesh K</creator><creator>LAWRIE, Gerald</creator><creator>REARDON, Michael J</creator><creator>LEE-JACKSON, Dorellyn</creator><creator>WINTERS, William L</creator><creator>SIVASUBRAMANIAN, Natarajan</creator><creator>MANN, Douglas L</creator><creator>ZOGHBI, William A</creator><general>Lippincott Williams & Wilkins</general><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>20020402</creationdate><title>Increased myocardial gene expression of tumor necrosis factor-α and nitric oxide synthase-2: A potential mechanism for depressed myocardial function in hibernating myocardium in humans</title><author>KALRA, Dinesh K ; XI ZHU ; RAMCHANDANI, Mahesh K ; LAWRIE, Gerald ; REARDON, Michael J ; LEE-JACKSON, Dorellyn ; WINTERS, William L ; SIVASUBRAMANIAN, Natarajan ; MANN, Douglas L ; ZOGHBI, William A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c203t-fdb568f6597455d22662fa43fb72ecb6e918c7a03014c411795f4fd6ea400d613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Biological and medical sciences</topic><topic>Cardiology. Vascular system</topic><topic>Coronary heart disease</topic><topic>Female</topic><topic>Heart</topic><topic>Heart - physiopathology</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Myocardial Stunning - diagnostic imaging</topic><topic>Myocardial Stunning - metabolism</topic><topic>Myocardial Stunning - physiopathology</topic><topic>Myocardium - metabolism</topic><topic>Nitric Oxide Synthase - biosynthesis</topic><topic>Nitric Oxide Synthase - genetics</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Nitrites - blood</topic><topic>Receptors, Adrenergic, beta - metabolism</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Transcriptional Activation</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Ultrasonography</topic><topic>Ventricular Dysfunction, Left - metabolism</topic><topic>Ventricular Dysfunction, Left - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KALRA, Dinesh K</creatorcontrib><creatorcontrib>XI ZHU</creatorcontrib><creatorcontrib>RAMCHANDANI, Mahesh K</creatorcontrib><creatorcontrib>LAWRIE, Gerald</creatorcontrib><creatorcontrib>REARDON, Michael J</creatorcontrib><creatorcontrib>LEE-JACKSON, Dorellyn</creatorcontrib><creatorcontrib>WINTERS, William L</creatorcontrib><creatorcontrib>SIVASUBRAMANIAN, Natarajan</creatorcontrib><creatorcontrib>MANN, Douglas L</creatorcontrib><creatorcontrib>ZOGHBI, William A</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>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KALRA, Dinesh K</au><au>XI ZHU</au><au>RAMCHANDANI, Mahesh K</au><au>LAWRIE, Gerald</au><au>REARDON, Michael J</au><au>LEE-JACKSON, Dorellyn</au><au>WINTERS, William L</au><au>SIVASUBRAMANIAN, Natarajan</au><au>MANN, Douglas L</au><au>ZOGHBI, William A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased myocardial gene expression of tumor necrosis factor-α and nitric oxide synthase-2: A potential mechanism for depressed myocardial function in hibernating myocardium in humans</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2002-04-02</date><risdate>2002</risdate><volume>105</volume><issue>13</issue><spage>1537</spage><epage>1540</epage><pages>1537-1540</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Whether cardioinhibitory cytokines are elevated in regions of hibernating myocardium and account in part for the depression in resting function is currently not known. Methods and Results- Thirteen patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperative dobutamine echocardiography (DE) and intraoperative myocardial biopsies. The numbers of copies of mRNA for the negatively inotropic cytokines tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (NOS2) were quantified by reverse transcription-polymerase chain reaction. In normal segments, myocardial TNF-alpha was barely detectable (1.2+/-0.4 copies per 10(6) copies of beta-actin). A 13.7-fold increase in myocardial TNF-alpha was observed in dysfunctional segments with a biphasic response to DE (contractile reserve and ischemia) and was highest (45.5-fold) in segments with ischemia and without contractile reserve (P<0.001). A similar graded increase was seen for NOS2. Cytokine results were also similar if analysis was performed using recovery of function at 3 months as the index of viability. The change in serum TNF-alpha and nitrite levels from baseline to 3 months after surgery correlated inversely with both the change in ejection fraction and the number of DE viable segments (r=-0.92 to -0.93; P<0.001).
TNF-alpha and NOS2 gene expression is regionally upregulated in hibernating myocardium to a level intermediate between that of normal regions and ischemic regions without contractile reserve. This, along with a decline in serum cytokine levels after revascularization proportional to the extent of myocardial viability, suggests a contributing role for cardioinhibitory cytokines in the observed depression of function seen in hibernating myocardium.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>11927517</pmid><doi>10.1161/01.CIR.0000013846.72805.7E</doi><tpages>4</tpages></addata></record> |
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| subjects | Biological and medical sciences Cardiology. Vascular system Coronary heart disease Female Heart Heart - physiopathology Humans Male Medical sciences Middle Aged Myocardial Stunning - diagnostic imaging Myocardial Stunning - metabolism Myocardial Stunning - physiopathology Myocardium - metabolism Nitric Oxide Synthase - biosynthesis Nitric Oxide Synthase - genetics Nitric Oxide Synthase Type II Nitrites - blood Receptors, Adrenergic, beta - metabolism RNA, Messenger - biosynthesis Transcriptional Activation Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - genetics Ultrasonography Ventricular Dysfunction, Left - metabolism Ventricular Dysfunction, Left - physiopathology |
| title | Increased myocardial gene expression of tumor necrosis factor-α and nitric oxide synthase-2: A potential mechanism for depressed myocardial function in hibernating myocardium in humans |
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