Hexarelin Treatment in Male Ghrelin Knockout Mice after Myocardial Infarction
Both ghrelin and the synthetic analog hexarelin are reported to possess cardioprotective actions that are mainly exerted through different receptors. However, their effects on acute myocardial infarction have not been compared in vivo. This study aimed to clarify whether hexarelin treatment can comp...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2013-10, Vol.154 (10), p.3847-3854 |
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| creator | Mao, Yuanjie Tokudome, Takeshi Kishimoto, Ichiro Otani, Kentaro Hosoda, Hiroshi Nagai, Chiaki Minamino, Naoto Miyazato, Mikiya Kangawa, Kenji |
| description | Both ghrelin and the synthetic analog hexarelin are reported to possess cardioprotective actions that are mainly exerted through different receptors. However, their effects on acute myocardial infarction have not been compared in vivo. This study aimed to clarify whether hexarelin treatment can compensate for ghrelin deficiency in ghrelin-knockout mice and to compare the effects of hexarelin (400 nmol/kg/d, sc) and equimolar ghrelin treatment after myocardial infarction. Myocardial infarction was produced by left coronary artery ligation in male ghrelin-knockout mice, which then received ghrelin, hexarelin, or vehicle treatment for 2 weeks. The mortality within 2 weeks was significantly lower in the hexarelin group (6.7%) and ghrelin group (14.3%) than in the vehicle group (50%) (P < .05). A comparison of cardiac function 2 weeks after infarction showed that in the ghrelin and hexarelin treatment groups, cardiac output was greater, whereas systolic function, represented by ejection fraction, and diastolic function, represented by dP/dt min (peak rate of pressure decline), were significantly superior compared with the vehicle group (P < .05). Hexarelin treatment was more effective than ghrelin treatment, as indicated by the ejection fraction, dP/dt max (peak rate of pressure rise), and dP/dt min. Telemetry recording and heart rate variability analysis demonstrated that sympathetic nervous activity was clearly suppressed in the hexarelin and ghrelin groups relative to the vehicle group. Our data demonstrated that hexarelin treatment can result in better heart function than ghrelin treatment 2 weeks after myocardial infarction in ghrelin-knockout mice, although both hormones have similar effects on heart rate variability and mortality. |
| doi_str_mv | 10.1210/en.2013-1291 |
| format | Article |
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However, their effects on acute myocardial infarction have not been compared in vivo. This study aimed to clarify whether hexarelin treatment can compensate for ghrelin deficiency in ghrelin-knockout mice and to compare the effects of hexarelin (400 nmol/kg/d, sc) and equimolar ghrelin treatment after myocardial infarction. Myocardial infarction was produced by left coronary artery ligation in male ghrelin-knockout mice, which then received ghrelin, hexarelin, or vehicle treatment for 2 weeks. The mortality within 2 weeks was significantly lower in the hexarelin group (6.7%) and ghrelin group (14.3%) than in the vehicle group (50%) (P < .05). A comparison of cardiac function 2 weeks after infarction showed that in the ghrelin and hexarelin treatment groups, cardiac output was greater, whereas systolic function, represented by ejection fraction, and diastolic function, represented by dP/dt min (peak rate of pressure decline), were significantly superior compared with the vehicle group (P < .05). Hexarelin treatment was more effective than ghrelin treatment, as indicated by the ejection fraction, dP/dt max (peak rate of pressure rise), and dP/dt min. Telemetry recording and heart rate variability analysis demonstrated that sympathetic nervous activity was clearly suppressed in the hexarelin and ghrelin groups relative to the vehicle group. Our data demonstrated that hexarelin treatment can result in better heart function than ghrelin treatment 2 weeks after myocardial infarction in ghrelin-knockout mice, although both hormones have similar effects on heart rate variability and mortality.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2013-1291</identifier><identifier>PMID: 23861368</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>Acetylation - drug effects ; Animals ; Biological and medical sciences ; Blood pressure ; Cardiac output ; Cardiac Output - drug effects ; Cardiology. Vascular system ; Cardiotonic Agents - therapeutic use ; Coronary artery ; Coronary heart disease ; Echocardiography ; Ejection fraction ; Fundamental and applied biological sciences. Psychology ; Ghrelin ; Ghrelin - analogs & derivatives ; Ghrelin - genetics ; Ghrelin - metabolism ; Ghrelin - therapeutic use ; Heart ; Heart - drug effects ; Heart - innervation ; Heart - physiopathology ; Heart attacks ; Heart function ; Heart rate ; Heart Rate - drug effects ; Hormones ; In vivo methods and tests ; Male ; Males ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mortality ; Myocardial infarction ; Myocardial Infarction - diagnostic imaging ; Myocardial Infarction - drug therapy ; Myocardial Infarction - metabolism ; Myocardial Infarction - physiopathology ; Myocarditis. Cardiomyopathies ; Myocardium - metabolism ; Oligopeptides - therapeutic use ; Protein Stability ; Stroke Volume - drug effects ; Survival Analysis ; Sympathetic Nervous System - drug effects ; Sympathetic Nervous System - metabolism ; Telemetry ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2013-10, Vol.154 (10), p.3847-3854</ispartof><rights>Copyright © 2013 by The Endocrine Society</rights><rights>Copyright © 2013 by The Endocrine Society 2013</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-ec4e3e1daea9fa14703961699f0d9a0254e28f4acceb2915b5daa220f1005c113</citedby><cites>FETCH-LOGICAL-c529t-ec4e3e1daea9fa14703961699f0d9a0254e28f4acceb2915b5daa220f1005c113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27739266$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23861368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao, Yuanjie</creatorcontrib><creatorcontrib>Tokudome, Takeshi</creatorcontrib><creatorcontrib>Kishimoto, Ichiro</creatorcontrib><creatorcontrib>Otani, Kentaro</creatorcontrib><creatorcontrib>Hosoda, Hiroshi</creatorcontrib><creatorcontrib>Nagai, Chiaki</creatorcontrib><creatorcontrib>Minamino, Naoto</creatorcontrib><creatorcontrib>Miyazato, Mikiya</creatorcontrib><creatorcontrib>Kangawa, Kenji</creatorcontrib><title>Hexarelin Treatment in Male Ghrelin Knockout Mice after Myocardial Infarction</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Both ghrelin and the synthetic analog hexarelin are reported to possess cardioprotective actions that are mainly exerted through different receptors. However, their effects on acute myocardial infarction have not been compared in vivo. This study aimed to clarify whether hexarelin treatment can compensate for ghrelin deficiency in ghrelin-knockout mice and to compare the effects of hexarelin (400 nmol/kg/d, sc) and equimolar ghrelin treatment after myocardial infarction. Myocardial infarction was produced by left coronary artery ligation in male ghrelin-knockout mice, which then received ghrelin, hexarelin, or vehicle treatment for 2 weeks. The mortality within 2 weeks was significantly lower in the hexarelin group (6.7%) and ghrelin group (14.3%) than in the vehicle group (50%) (P < .05). A comparison of cardiac function 2 weeks after infarction showed that in the ghrelin and hexarelin treatment groups, cardiac output was greater, whereas systolic function, represented by ejection fraction, and diastolic function, represented by dP/dt min (peak rate of pressure decline), were significantly superior compared with the vehicle group (P < .05). Hexarelin treatment was more effective than ghrelin treatment, as indicated by the ejection fraction, dP/dt max (peak rate of pressure rise), and dP/dt min. Telemetry recording and heart rate variability analysis demonstrated that sympathetic nervous activity was clearly suppressed in the hexarelin and ghrelin groups relative to the vehicle group. Our data demonstrated that hexarelin treatment can result in better heart function than ghrelin treatment 2 weeks after myocardial infarction in ghrelin-knockout mice, although both hormones have similar effects on heart rate variability and mortality.</description><subject>Acetylation - drug effects</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood pressure</subject><subject>Cardiac output</subject><subject>Cardiac Output - drug effects</subject><subject>Cardiology. Vascular system</subject><subject>Cardiotonic Agents - therapeutic use</subject><subject>Coronary artery</subject><subject>Coronary heart disease</subject><subject>Echocardiography</subject><subject>Ejection fraction</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Ghrelin</subject><subject>Ghrelin - analogs & derivatives</subject><subject>Ghrelin - genetics</subject><subject>Ghrelin - metabolism</subject><subject>Ghrelin - therapeutic use</subject><subject>Heart</subject><subject>Heart - drug effects</subject><subject>Heart - innervation</subject><subject>Heart - physiopathology</subject><subject>Heart attacks</subject><subject>Heart function</subject><subject>Heart rate</subject><subject>Heart Rate - drug effects</subject><subject>Hormones</subject><subject>In vivo methods and tests</subject><subject>Male</subject><subject>Males</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mortality</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - diagnostic imaging</subject><subject>Myocardial Infarction - drug therapy</subject><subject>Myocardial Infarction - metabolism</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>Myocardium - metabolism</subject><subject>Oligopeptides - therapeutic use</subject><subject>Protein Stability</subject><subject>Stroke Volume - drug effects</subject><subject>Survival Analysis</subject><subject>Sympathetic Nervous System - drug effects</subject><subject>Sympathetic Nervous System - metabolism</subject><subject>Telemetry</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10M9LHTEQB_Aglfpqe_NcForowbWZJPsjRxGrUh-92HOYl53QtfuS12QX6n9vHvtaQfQUJvkwmfkydgT8HATwr-TPBQdZgtCwxxagVVU20PB3bMG3940QzQH7kNJDLpVS8j07ELKtQdbtgi1v6C9GGnpf3EfCcU1-LHKxxIGK61_zy3cf7O8wjcWyt1SgGykWy8dgMXY9DsWtdxjt2Af_ke07HBJ92p2H7Oe3q_vLm_Lux_Xt5cVdaSuhx5KsIknQIaF2CKrhUtdQa-14p5GLSpFonUJraZW3qlZVhygEd8B5ZQHkITud-25i-DNRGs26T5aGAT2FKRlQsmqVqoXO9MsL-hCm6PN0RoLkteBN22Z1NisbQ0qRnNnEfo3x0QA325gNebON2Wxjzvzzrum0WlP3H__LNYPjHcBkcXARve3Ts2saqUVdZ3cyuzBt3vqy3H0pZ0m-Czb2njaRUnre5tVBnwBRSqCA</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Mao, Yuanjie</creator><creator>Tokudome, Takeshi</creator><creator>Kishimoto, Ichiro</creator><creator>Otani, Kentaro</creator><creator>Hosoda, Hiroshi</creator><creator>Nagai, Chiaki</creator><creator>Minamino, Naoto</creator><creator>Miyazato, Mikiya</creator><creator>Kangawa, Kenji</creator><general>Endocrine Society</general><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>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20131001</creationdate><title>Hexarelin Treatment in Male Ghrelin Knockout Mice after Myocardial Infarction</title><author>Mao, Yuanjie ; Tokudome, Takeshi ; Kishimoto, Ichiro ; Otani, Kentaro ; Hosoda, Hiroshi ; Nagai, Chiaki ; Minamino, Naoto ; Miyazato, Mikiya ; Kangawa, Kenji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c529t-ec4e3e1daea9fa14703961699f0d9a0254e28f4acceb2915b5daa220f1005c113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetylation - drug effects</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood pressure</topic><topic>Cardiac output</topic><topic>Cardiac Output - drug effects</topic><topic>Cardiology. Vascular system</topic><topic>Cardiotonic Agents - therapeutic use</topic><topic>Coronary artery</topic><topic>Coronary heart disease</topic><topic>Echocardiography</topic><topic>Ejection fraction</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Ghrelin</topic><topic>Ghrelin - analogs & derivatives</topic><topic>Ghrelin - genetics</topic><topic>Ghrelin - metabolism</topic><topic>Ghrelin - therapeutic use</topic><topic>Heart</topic><topic>Heart - drug effects</topic><topic>Heart - innervation</topic><topic>Heart - physiopathology</topic><topic>Heart attacks</topic><topic>Heart function</topic><topic>Heart rate</topic><topic>Heart Rate - drug effects</topic><topic>Hormones</topic><topic>In vivo methods and tests</topic><topic>Male</topic><topic>Males</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mortality</topic><topic>Myocardial infarction</topic><topic>Myocardial Infarction - diagnostic imaging</topic><topic>Myocardial Infarction - drug therapy</topic><topic>Myocardial Infarction - metabolism</topic><topic>Myocardial Infarction - physiopathology</topic><topic>Myocarditis. Cardiomyopathies</topic><topic>Myocardium - metabolism</topic><topic>Oligopeptides - therapeutic use</topic><topic>Protein Stability</topic><topic>Stroke Volume - drug effects</topic><topic>Survival Analysis</topic><topic>Sympathetic Nervous System - drug effects</topic><topic>Sympathetic Nervous System - metabolism</topic><topic>Telemetry</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mao, Yuanjie</creatorcontrib><creatorcontrib>Tokudome, Takeshi</creatorcontrib><creatorcontrib>Kishimoto, Ichiro</creatorcontrib><creatorcontrib>Otani, Kentaro</creatorcontrib><creatorcontrib>Hosoda, Hiroshi</creatorcontrib><creatorcontrib>Nagai, Chiaki</creatorcontrib><creatorcontrib>Minamino, Naoto</creatorcontrib><creatorcontrib>Miyazato, Mikiya</creatorcontrib><creatorcontrib>Kangawa, Kenji</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>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mao, Yuanjie</au><au>Tokudome, Takeshi</au><au>Kishimoto, Ichiro</au><au>Otani, Kentaro</au><au>Hosoda, Hiroshi</au><au>Nagai, Chiaki</au><au>Minamino, Naoto</au><au>Miyazato, Mikiya</au><au>Kangawa, Kenji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hexarelin Treatment in Male Ghrelin Knockout Mice after Myocardial Infarction</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>154</volume><issue>10</issue><spage>3847</spage><epage>3854</epage><pages>3847-3854</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Both ghrelin and the synthetic analog hexarelin are reported to possess cardioprotective actions that are mainly exerted through different receptors. However, their effects on acute myocardial infarction have not been compared in vivo. This study aimed to clarify whether hexarelin treatment can compensate for ghrelin deficiency in ghrelin-knockout mice and to compare the effects of hexarelin (400 nmol/kg/d, sc) and equimolar ghrelin treatment after myocardial infarction. Myocardial infarction was produced by left coronary artery ligation in male ghrelin-knockout mice, which then received ghrelin, hexarelin, or vehicle treatment for 2 weeks. The mortality within 2 weeks was significantly lower in the hexarelin group (6.7%) and ghrelin group (14.3%) than in the vehicle group (50%) (P < .05). A comparison of cardiac function 2 weeks after infarction showed that in the ghrelin and hexarelin treatment groups, cardiac output was greater, whereas systolic function, represented by ejection fraction, and diastolic function, represented by dP/dt min (peak rate of pressure decline), were significantly superior compared with the vehicle group (P < .05). Hexarelin treatment was more effective than ghrelin treatment, as indicated by the ejection fraction, dP/dt max (peak rate of pressure rise), and dP/dt min. Telemetry recording and heart rate variability analysis demonstrated that sympathetic nervous activity was clearly suppressed in the hexarelin and ghrelin groups relative to the vehicle group. Our data demonstrated that hexarelin treatment can result in better heart function than ghrelin treatment 2 weeks after myocardial infarction in ghrelin-knockout mice, although both hormones have similar effects on heart rate variability and mortality.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>23861368</pmid><doi>10.1210/en.2013-1291</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Acetylation - drug effects Animals Biological and medical sciences Blood pressure Cardiac output Cardiac Output - drug effects Cardiology. Vascular system Cardiotonic Agents - therapeutic use Coronary artery Coronary heart disease Echocardiography Ejection fraction Fundamental and applied biological sciences. Psychology Ghrelin Ghrelin - analogs & derivatives Ghrelin - genetics Ghrelin - metabolism Ghrelin - therapeutic use Heart Heart - drug effects Heart - innervation Heart - physiopathology Heart attacks Heart function Heart rate Heart Rate - drug effects Hormones In vivo methods and tests Male Males Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Mortality Myocardial infarction Myocardial Infarction - diagnostic imaging Myocardial Infarction - drug therapy Myocardial Infarction - metabolism Myocardial Infarction - physiopathology Myocarditis. Cardiomyopathies Myocardium - metabolism Oligopeptides - therapeutic use Protein Stability Stroke Volume - drug effects Survival Analysis Sympathetic Nervous System - drug effects Sympathetic Nervous System - metabolism Telemetry Vertebrates: endocrinology |
| title | Hexarelin Treatment in Male Ghrelin Knockout Mice after Myocardial Infarction |
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