Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction
The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, s...
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| Veröffentlicht in: | Circulation research 2007-04, Vol.100 (7), p.1079-1088 |
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| creator | de Waard, Monique C van der Velden, Jolanda Bito, Virginie Ozdemir, Semir Biesmans, Liesbeth Boontje, Nicky M Dekkers, Dick H.W Schoonderwoerd, Kees Schuurbiers, Hans C.H de Crom, Rini Stienen, Ger J.M Sipido, Karin R Lamers, Jos M.J Duncker, Dirk J |
| description | The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8±1 to 12±1%, and LVdP/dtP30 from 5295±207 to 5794±207 mm Hg/s (both P |
| doi_str_mv | 10.1161/01.RES.0000262655.16373.37 |
| format | Article |
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Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8±1 to 12±1%, and LVdP/dtP30 from 5295±207 to 5794±207 mm Hg/s (both P<0.05), and reduced pulmonary congestion. These global effects of exercise were associated with normalization of the MI-induced increase in myofilament Ca-sensitivity (ΔpCa50=0.037). This effect of exercise was PKA-mediated and likely because of improved β1-adrenergic signaling, as suggested by the increased β1-adrenoceptor protein (48%) and cAMP levels (36%; all P<0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (Fmax increased from 14.3±0.7 to 18.3±0.8 kN/mP<0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.1±0.3 to 7.0±0.6%; P<0.05). Furthermore, exercise reduced diastolic Ca-concentrations (by ∼30%, P<0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca-transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because of improved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling, but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilament function.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.RES.0000262655.16373.37</identifier><identifier>PMID: 17347478</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Actin Cytoskeleton - metabolism ; Animals ; Biological and medical sciences ; Blotting, Western ; Cardiology. Vascular system ; Coronary heart disease ; Cyclic AMP - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Heart ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Myocardial Contraction ; Myocardial Infarction - mortality ; Myocardial Infarction - physiopathology ; Myocytes, Cardiac - metabolism ; Permeability ; Phosphorylation ; Physical Conditioning, Animal ; Proteins - metabolism ; Severity of Illness Index ; Time Factors ; Ventricular Dysfunction, Left - physiopathology ; Ventricular Function, Left ; Ventricular Remodeling ; Vertebrates: cardiovascular system</subject><ispartof>Circulation research, 2007-04, Vol.100 (7), p.1079-1088</ispartof><rights>2007 American Heart Association, Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4717-6094fb301f5c6676357255fa6972a97ef24e7de256563c2050af78e39fbbbee23</citedby><cites>FETCH-LOGICAL-c4717-6094fb301f5c6676357255fa6972a97ef24e7de256563c2050af78e39fbbbee23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18683564$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17347478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Waard, Monique C</creatorcontrib><creatorcontrib>van der Velden, Jolanda</creatorcontrib><creatorcontrib>Bito, Virginie</creatorcontrib><creatorcontrib>Ozdemir, Semir</creatorcontrib><creatorcontrib>Biesmans, Liesbeth</creatorcontrib><creatorcontrib>Boontje, Nicky M</creatorcontrib><creatorcontrib>Dekkers, Dick H.W</creatorcontrib><creatorcontrib>Schoonderwoerd, Kees</creatorcontrib><creatorcontrib>Schuurbiers, Hans C.H</creatorcontrib><creatorcontrib>de Crom, Rini</creatorcontrib><creatorcontrib>Stienen, Ger J.M</creatorcontrib><creatorcontrib>Sipido, Karin R</creatorcontrib><creatorcontrib>Lamers, Jos M.J</creatorcontrib><creatorcontrib>Duncker, Dirk J</creatorcontrib><title>Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8±1 to 12±1%, and LVdP/dtP30 from 5295±207 to 5794±207 mm Hg/s (both P<0.05), and reduced pulmonary congestion. These global effects of exercise were associated with normalization of the MI-induced increase in myofilament Ca-sensitivity (ΔpCa50=0.037). This effect of exercise was PKA-mediated and likely because of improved β1-adrenergic signaling, as suggested by the increased β1-adrenoceptor protein (48%) and cAMP levels (36%; all P<0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (Fmax increased from 14.3±0.7 to 18.3±0.8 kN/mP<0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.1±0.3 to 7.0±0.6%; P<0.05). Furthermore, exercise reduced diastolic Ca-concentrations (by ∼30%, P<0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca-transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because of improved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling, but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilament function.</description><subject>Actin Cytoskeleton - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cardiology. Vascular system</subject><subject>Coronary heart disease</subject><subject>Cyclic AMP - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Heart</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Myocardial Contraction</subject><subject>Myocardial Infarction - mortality</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Permeability</subject><subject>Phosphorylation</subject><subject>Physical Conditioning, Animal</subject><subject>Proteins - metabolism</subject><subject>Severity of Illness Index</subject><subject>Time Factors</subject><subject>Ventricular Dysfunction, Left - physiopathology</subject><subject>Ventricular Function, Left</subject><subject>Ventricular Remodeling</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0ctuEzEUgGELgWgaeAVkIdFdgj2-ZVggVSWFSikgKLC0TpzjxuDxBHtGbXgNXphpE5QlWLK8-Y5t6SfkOWdTzjV_yfj00_zzlA2r0pVWasq1MGIqzAMy4qqSE6kMf0hGA6gnRgh2RI5L-c4Yl6KqH5MjboQ00sxG5PccctzS-S1mFwrSqwwhhXRN37e5gRh-YaGX29aHCA2mjp73yXWhTRTSip52HaYeusEs0Hf06yBycH2ETD_2zYa-2Rb_dyAkehkc0m-hW1OgC8jXeHe1g7wKEOlF8pDv6RPyyEMs-HR_jsmX8_nV2bvJ4sPbi7PTxcRJw81Es1r6pWDcK6e10UKZSikPujYV1AZ9JdGssFJaaeEqphh4M0NR--VyiViJMTnZ3bvJ7c8eS2ebUBzGCAnbvljDhKmZ_DfktVYzOUQYk1c76HJbSkZvNzk0kLeWM3vXzjJuh3b20M7et7PDHpNn-1f6ZYOrw-g-1gBe7AEUB9FnSEOzg5vpmVBaDu71zt20scNcfsT-BrNdI8Ru_T8_-QPu47cn</recordid><startdate>20070413</startdate><enddate>20070413</enddate><creator>de Waard, Monique C</creator><creator>van der Velden, Jolanda</creator><creator>Bito, Virginie</creator><creator>Ozdemir, Semir</creator><creator>Biesmans, Liesbeth</creator><creator>Boontje, Nicky M</creator><creator>Dekkers, Dick H.W</creator><creator>Schoonderwoerd, Kees</creator><creator>Schuurbiers, Hans C.H</creator><creator>de Crom, Rini</creator><creator>Stienen, Ger J.M</creator><creator>Sipido, Karin R</creator><creator>Lamers, Jos M.J</creator><creator>Duncker, Dirk J</creator><general>American Heart Association, Inc</general><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>7TS</scope><scope>7X8</scope></search><sort><creationdate>20070413</creationdate><title>Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction</title><author>de Waard, Monique C ; van der Velden, Jolanda ; Bito, Virginie ; Ozdemir, Semir ; Biesmans, Liesbeth ; Boontje, Nicky M ; Dekkers, Dick H.W ; Schoonderwoerd, Kees ; Schuurbiers, Hans C.H ; de Crom, Rini ; Stienen, Ger J.M ; Sipido, Karin R ; Lamers, Jos M.J ; Duncker, Dirk J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4717-6094fb301f5c6676357255fa6972a97ef24e7de256563c2050af78e39fbbbee23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Actin Cytoskeleton - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cardiology. Vascular system</topic><topic>Coronary heart disease</topic><topic>Cyclic AMP - metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Heart</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Myocardial Contraction</topic><topic>Myocardial Infarction - mortality</topic><topic>Myocardial Infarction - physiopathology</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Permeability</topic><topic>Phosphorylation</topic><topic>Physical Conditioning, Animal</topic><topic>Proteins - metabolism</topic><topic>Severity of Illness Index</topic><topic>Time Factors</topic><topic>Ventricular Dysfunction, Left - physiopathology</topic><topic>Ventricular Function, Left</topic><topic>Ventricular Remodeling</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Waard, Monique C</creatorcontrib><creatorcontrib>van der Velden, Jolanda</creatorcontrib><creatorcontrib>Bito, Virginie</creatorcontrib><creatorcontrib>Ozdemir, Semir</creatorcontrib><creatorcontrib>Biesmans, Liesbeth</creatorcontrib><creatorcontrib>Boontje, Nicky M</creatorcontrib><creatorcontrib>Dekkers, Dick H.W</creatorcontrib><creatorcontrib>Schoonderwoerd, Kees</creatorcontrib><creatorcontrib>Schuurbiers, Hans C.H</creatorcontrib><creatorcontrib>de Crom, Rini</creatorcontrib><creatorcontrib>Stienen, Ger J.M</creatorcontrib><creatorcontrib>Sipido, Karin R</creatorcontrib><creatorcontrib>Lamers, Jos M.J</creatorcontrib><creatorcontrib>Duncker, Dirk J</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>Physical Education Index</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Waard, Monique C</au><au>van der Velden, Jolanda</au><au>Bito, Virginie</au><au>Ozdemir, Semir</au><au>Biesmans, Liesbeth</au><au>Boontje, Nicky M</au><au>Dekkers, Dick H.W</au><au>Schoonderwoerd, Kees</au><au>Schuurbiers, Hans C.H</au><au>de Crom, Rini</au><au>Stienen, Ger J.M</au><au>Sipido, Karin R</au><au>Lamers, Jos M.J</au><au>Duncker, Dirk J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2007-04-13</date><risdate>2007</risdate><volume>100</volume><issue>7</issue><spage>1079</spage><epage>1088</epage><pages>1079-1088</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8±1 to 12±1%, and LVdP/dtP30 from 5295±207 to 5794±207 mm Hg/s (both P<0.05), and reduced pulmonary congestion. These global effects of exercise were associated with normalization of the MI-induced increase in myofilament Ca-sensitivity (ΔpCa50=0.037). This effect of exercise was PKA-mediated and likely because of improved β1-adrenergic signaling, as suggested by the increased β1-adrenoceptor protein (48%) and cAMP levels (36%; all P<0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (Fmax increased from 14.3±0.7 to 18.3±0.8 kN/mP<0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.1±0.3 to 7.0±0.6%; P<0.05). Furthermore, exercise reduced diastolic Ca-concentrations (by ∼30%, P<0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca-transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because of improved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling, but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilament function.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>17347478</pmid><doi>10.1161/01.RES.0000262655.16373.37</doi><tpages>10</tpages></addata></record> |
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| subjects | Actin Cytoskeleton - metabolism Animals Biological and medical sciences Blotting, Western Cardiology. Vascular system Coronary heart disease Cyclic AMP - metabolism Female Fundamental and applied biological sciences. Psychology Heart Heart failure, cardiogenic pulmonary edema, cardiac enlargement Male Medical sciences Mice Mice, Inbred C57BL Myocardial Contraction Myocardial Infarction - mortality Myocardial Infarction - physiopathology Myocytes, Cardiac - metabolism Permeability Phosphorylation Physical Conditioning, Animal Proteins - metabolism Severity of Illness Index Time Factors Ventricular Dysfunction, Left - physiopathology Ventricular Function, Left Ventricular Remodeling Vertebrates: cardiovascular system |
| title | Early Exercise Training Normalizes Myofilament Function and Attenuates Left Ventricular Pump Dysfunction in Mice With a Large Myocardial Infarction |
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