Rapid endotoxin-induced alterations in myocardial calcium handling: Obligatory role of cardiac TNF-α
Bacterial endotoxin (lipopolysaccharide [LPS]) induces septic shock and depressed myocardial contractility. The mechanism of LPS-mediated cardiac dysfunction remains controversial. We hypothesized that LPS exerts significant effects on myocardial excitation-contraction coupling by rapid stimulation...
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| Veröffentlicht in: | Anesthesiology (Philadelphia) 2001-12, Vol.95 (6), p.1396-1405 |
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| creator | STAMM, Christof COWAN, Douglas B FRIEHS, Ingeborg NORIA, Sabrena DEL NIDO, Pedro J MCGOWAN, Francis X |
| description | Bacterial endotoxin (lipopolysaccharide [LPS]) induces septic shock and depressed myocardial contractility. The mechanism of LPS-mediated cardiac dysfunction remains controversial. We hypothesized that LPS exerts significant effects on myocardial excitation-contraction coupling by rapid stimulation of tumor necrosis factor alpha (TNF-alpha) expression in the heart.
Isolated rat hearts were studied with and without recirculation of cell-free perfusate. The effects of LPS, exogenous TNF-alpha, anti-TNF-alpha antibody, and ceramidase inhibition were examined. Measurements included myocardial uptake of LPS, left ventricular contractility, myocardial oxygen consumption, intracellular calcium [Ca2+] cycling, and TNF-alpha concentrations in coronary perfusate and myocardium.
Lipopolysaccharide was rapidly taken up by the perfused heart. With non-recirculating perfusion, LPS had no effect on contractility, oxygen consumption, coronary vascular resistance, or intracellular free calcium concentration ([Ca2+]i). However, with recirculating perfusion contractility was significantly impaired after 30 min of LPS, associated with lower [Ca2+]i levels and attenuated systolic rise in [Ca2+]i. Significant amounts of TNF-alpha accumulated in recirculating perfusate and myocardial tissue from LPS-perfused hearts. Ceramidase inhibition or neutralizing anti-TNF-alpha antibody inhibited the effects of LPS on contractility and [Ca2+]i. Recombinant rat TNF-alpha mimicked the LPS effects with faster onset.
Lipopolysaccharide exerts rapid, negative inotropic effects on the isolated whole rat heart. The reduction in contractility is associated with depressed intracellular calcium cycling. In response to LPS, TNF-alpha is rapidly released from the heart and mediates the effects of LPS via the sphingomyelinase pathway. The present study for the first time directly links LPS-stimulated TNF-alpha production, abnormal calcium cycling, and decreased contractility in intact hearts. |
| doi_str_mv | 10.1097/00000542-200112000-00019 |
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Isolated rat hearts were studied with and without recirculation of cell-free perfusate. The effects of LPS, exogenous TNF-alpha, anti-TNF-alpha antibody, and ceramidase inhibition were examined. Measurements included myocardial uptake of LPS, left ventricular contractility, myocardial oxygen consumption, intracellular calcium [Ca2+] cycling, and TNF-alpha concentrations in coronary perfusate and myocardium.
Lipopolysaccharide was rapidly taken up by the perfused heart. With non-recirculating perfusion, LPS had no effect on contractility, oxygen consumption, coronary vascular resistance, or intracellular free calcium concentration ([Ca2+]i). However, with recirculating perfusion contractility was significantly impaired after 30 min of LPS, associated with lower [Ca2+]i levels and attenuated systolic rise in [Ca2+]i. Significant amounts of TNF-alpha accumulated in recirculating perfusate and myocardial tissue from LPS-perfused hearts. Ceramidase inhibition or neutralizing anti-TNF-alpha antibody inhibited the effects of LPS on contractility and [Ca2+]i. Recombinant rat TNF-alpha mimicked the LPS effects with faster onset.
Lipopolysaccharide exerts rapid, negative inotropic effects on the isolated whole rat heart. The reduction in contractility is associated with depressed intracellular calcium cycling. In response to LPS, TNF-alpha is rapidly released from the heart and mediates the effects of LPS via the sphingomyelinase pathway. The present study for the first time directly links LPS-stimulated TNF-alpha production, abnormal calcium cycling, and decreased contractility in intact hearts.</description><identifier>ISSN: 0003-3022</identifier><identifier>EISSN: 1528-1175</identifier><identifier>DOI: 10.1097/00000542-200112000-00019</identifier><identifier>PMID: 11748398</identifier><identifier>CODEN: ANESAV</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antibodies, Blocking - pharmacology ; Biological and medical sciences ; Calcium - metabolism ; Emergency and intensive care: infection, septic shock ; Endotoxins - antagonists & inhibitors ; Endotoxins - pharmacology ; In Vitro Techniques ; Intensive care medicine ; Lipopolysaccharides - antagonists & inhibitors ; Lipopolysaccharides - pharmacology ; Male ; Medical sciences ; Membranes - drug effects ; Membranes - metabolism ; Myocardial Contraction - drug effects ; Myocardium - metabolism ; Myofibrils - drug effects ; Myofibrils - metabolism ; Rats ; Signal Transduction - drug effects ; Tumor Necrosis Factor-alpha - antagonists & inhibitors ; Tumor Necrosis Factor-alpha - physiology</subject><ispartof>Anesthesiology (Philadelphia), 2001-12, Vol.95 (6), p.1396-1405</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14119069$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11748398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>STAMM, Christof</creatorcontrib><creatorcontrib>COWAN, Douglas B</creatorcontrib><creatorcontrib>FRIEHS, Ingeborg</creatorcontrib><creatorcontrib>NORIA, Sabrena</creatorcontrib><creatorcontrib>DEL NIDO, Pedro J</creatorcontrib><creatorcontrib>MCGOWAN, Francis X</creatorcontrib><title>Rapid endotoxin-induced alterations in myocardial calcium handling: Obligatory role of cardiac TNF-α</title><title>Anesthesiology (Philadelphia)</title><addtitle>Anesthesiology</addtitle><description>Bacterial endotoxin (lipopolysaccharide [LPS]) induces septic shock and depressed myocardial contractility. The mechanism of LPS-mediated cardiac dysfunction remains controversial. We hypothesized that LPS exerts significant effects on myocardial excitation-contraction coupling by rapid stimulation of tumor necrosis factor alpha (TNF-alpha) expression in the heart.
Isolated rat hearts were studied with and without recirculation of cell-free perfusate. The effects of LPS, exogenous TNF-alpha, anti-TNF-alpha antibody, and ceramidase inhibition were examined. Measurements included myocardial uptake of LPS, left ventricular contractility, myocardial oxygen consumption, intracellular calcium [Ca2+] cycling, and TNF-alpha concentrations in coronary perfusate and myocardium.
Lipopolysaccharide was rapidly taken up by the perfused heart. With non-recirculating perfusion, LPS had no effect on contractility, oxygen consumption, coronary vascular resistance, or intracellular free calcium concentration ([Ca2+]i). However, with recirculating perfusion contractility was significantly impaired after 30 min of LPS, associated with lower [Ca2+]i levels and attenuated systolic rise in [Ca2+]i. Significant amounts of TNF-alpha accumulated in recirculating perfusate and myocardial tissue from LPS-perfused hearts. Ceramidase inhibition or neutralizing anti-TNF-alpha antibody inhibited the effects of LPS on contractility and [Ca2+]i. Recombinant rat TNF-alpha mimicked the LPS effects with faster onset.
Lipopolysaccharide exerts rapid, negative inotropic effects on the isolated whole rat heart. The reduction in contractility is associated with depressed intracellular calcium cycling. In response to LPS, TNF-alpha is rapidly released from the heart and mediates the effects of LPS via the sphingomyelinase pathway. The present study for the first time directly links LPS-stimulated TNF-alpha production, abnormal calcium cycling, and decreased contractility in intact hearts.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antibodies, Blocking - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Emergency and intensive care: infection, septic shock</subject><subject>Endotoxins - antagonists & inhibitors</subject><subject>Endotoxins - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Intensive care medicine</subject><subject>Lipopolysaccharides - antagonists & inhibitors</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membranes - drug effects</subject><subject>Membranes - metabolism</subject><subject>Myocardial Contraction - drug effects</subject><subject>Myocardium - metabolism</subject><subject>Myofibrils - drug effects</subject><subject>Myofibrils - metabolism</subject><subject>Rats</subject><subject>Signal Transduction - drug effects</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><subject>Tumor Necrosis Factor-alpha - physiology</subject><issn>0003-3022</issn><issn>1528-1175</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkN1KHTEQgIO01FPtK0hu2ru0-dndJN4V0bYgFUSvlzn50ZRscprsQs9j-SI-k9FzrAOZIZlvMvAhhBn9yqiW3-hz9B0nnFLGWqKkHaYP0Ir1XBHGZP8OrdqbIIJyfog-1vqnXWUv1Ad02PqdElqtkLuGTbDYJZvn_C8kEpJdjLMY4uwKzCGnikPC0zYbKDZAxAaiCcuE7yHZGNLdKb5ax3AHcy5bXHJ0OHu8gw2--X1BHh-O0XsPsbpP-3qEbi_Ob85-ksurH7_Ovl8Sw9UwE-GZEDCAtHSQDqhgTlvo-h70YDsvtPHcy14bp7Sl3K2pXIMUSmluvZOdOEJfdv9uSv67uDqPU6jGxQjJ5aWOkoth4Io1UO1AU3KtxflxU8IEZTsyOj4rHl8Vj_8Vjy-K2-jJfseynpx9G9w7bcDnPQC1ufIFkgn1jesY03TQ4gmcs4T3</recordid><startdate>20011201</startdate><enddate>20011201</enddate><creator>STAMM, Christof</creator><creator>COWAN, Douglas B</creator><creator>FRIEHS, Ingeborg</creator><creator>NORIA, Sabrena</creator><creator>DEL NIDO, Pedro J</creator><creator>MCGOWAN, Francis X</creator><general>Lippincott</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>20011201</creationdate><title>Rapid endotoxin-induced alterations in myocardial calcium handling: Obligatory role of cardiac TNF-α</title><author>STAMM, Christof ; COWAN, Douglas B ; FRIEHS, Ingeborg ; NORIA, Sabrena ; DEL NIDO, Pedro J ; MCGOWAN, Francis X</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c286t-3f133a6a7d067ea031e9da455a96d4f39cf2f759ce89d02eb07ba738892dfe743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Antibodies, Blocking - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Emergency and intensive care: infection, septic shock</topic><topic>Endotoxins - antagonists & inhibitors</topic><topic>Endotoxins - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Intensive care medicine</topic><topic>Lipopolysaccharides - antagonists & inhibitors</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membranes - drug effects</topic><topic>Membranes - metabolism</topic><topic>Myocardial Contraction - drug effects</topic><topic>Myocardium - metabolism</topic><topic>Myofibrils - drug effects</topic><topic>Myofibrils - metabolism</topic><topic>Rats</topic><topic>Signal Transduction - drug effects</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><topic>Tumor Necrosis Factor-alpha - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>STAMM, Christof</creatorcontrib><creatorcontrib>COWAN, Douglas B</creatorcontrib><creatorcontrib>FRIEHS, Ingeborg</creatorcontrib><creatorcontrib>NORIA, Sabrena</creatorcontrib><creatorcontrib>DEL NIDO, Pedro J</creatorcontrib><creatorcontrib>MCGOWAN, Francis X</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>Anesthesiology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>STAMM, Christof</au><au>COWAN, Douglas B</au><au>FRIEHS, Ingeborg</au><au>NORIA, Sabrena</au><au>DEL NIDO, Pedro J</au><au>MCGOWAN, Francis X</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid endotoxin-induced alterations in myocardial calcium handling: Obligatory role of cardiac TNF-α</atitle><jtitle>Anesthesiology (Philadelphia)</jtitle><addtitle>Anesthesiology</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>95</volume><issue>6</issue><spage>1396</spage><epage>1405</epage><pages>1396-1405</pages><issn>0003-3022</issn><eissn>1528-1175</eissn><coden>ANESAV</coden><abstract>Bacterial endotoxin (lipopolysaccharide [LPS]) induces septic shock and depressed myocardial contractility. The mechanism of LPS-mediated cardiac dysfunction remains controversial. We hypothesized that LPS exerts significant effects on myocardial excitation-contraction coupling by rapid stimulation of tumor necrosis factor alpha (TNF-alpha) expression in the heart.
Isolated rat hearts were studied with and without recirculation of cell-free perfusate. The effects of LPS, exogenous TNF-alpha, anti-TNF-alpha antibody, and ceramidase inhibition were examined. Measurements included myocardial uptake of LPS, left ventricular contractility, myocardial oxygen consumption, intracellular calcium [Ca2+] cycling, and TNF-alpha concentrations in coronary perfusate and myocardium.
Lipopolysaccharide was rapidly taken up by the perfused heart. With non-recirculating perfusion, LPS had no effect on contractility, oxygen consumption, coronary vascular resistance, or intracellular free calcium concentration ([Ca2+]i). However, with recirculating perfusion contractility was significantly impaired after 30 min of LPS, associated with lower [Ca2+]i levels and attenuated systolic rise in [Ca2+]i. Significant amounts of TNF-alpha accumulated in recirculating perfusate and myocardial tissue from LPS-perfused hearts. Ceramidase inhibition or neutralizing anti-TNF-alpha antibody inhibited the effects of LPS on contractility and [Ca2+]i. Recombinant rat TNF-alpha mimicked the LPS effects with faster onset.
Lipopolysaccharide exerts rapid, negative inotropic effects on the isolated whole rat heart. The reduction in contractility is associated with depressed intracellular calcium cycling. In response to LPS, TNF-alpha is rapidly released from the heart and mediates the effects of LPS via the sphingomyelinase pathway. The present study for the first time directly links LPS-stimulated TNF-alpha production, abnormal calcium cycling, and decreased contractility in intact hearts.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>11748398</pmid><doi>10.1097/00000542-200112000-00019</doi><tpages>10</tpages></addata></record> |
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| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antibodies, Blocking - pharmacology Biological and medical sciences Calcium - metabolism Emergency and intensive care: infection, septic shock Endotoxins - antagonists & inhibitors Endotoxins - pharmacology In Vitro Techniques Intensive care medicine Lipopolysaccharides - antagonists & inhibitors Lipopolysaccharides - pharmacology Male Medical sciences Membranes - drug effects Membranes - metabolism Myocardial Contraction - drug effects Myocardium - metabolism Myofibrils - drug effects Myofibrils - metabolism Rats Signal Transduction - drug effects Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - physiology |
| title | Rapid endotoxin-induced alterations in myocardial calcium handling: Obligatory role of cardiac TNF-α |
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