author_facet Fraccarollo, Daniela
Hu, Kai
Galuppo, Paolo
Gaudron, Peter
Ertl, Georg
Fraccarollo, Daniela
Hu, Kai
Galuppo, Paolo
Gaudron, Peter
Ertl, Georg
author Fraccarollo, Daniela
Hu, Kai
Galuppo, Paolo
Gaudron, Peter
Ertl, Georg
spellingShingle Fraccarollo, Daniela
Hu, Kai
Galuppo, Paolo
Gaudron, Peter
Ertl, Georg
Circulation
Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
Physiology (medical)
Cardiology and Cardiovascular Medicine
author_sort fraccarollo, daniela
spelling Fraccarollo, Daniela Hu, Kai Galuppo, Paolo Gaudron, Peter Ertl, Georg 0009-7322 1524-4539 Ovid Technologies (Wolters Kluwer Health) Physiology (medical) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/01.cir.96.11.3963 <jats:p> <jats:italic>Background</jats:italic> Left ventricular dilatation after myocardial infarction is associated with impaired ventricular function and heart failure and has important implications for survival. The purpose of this study was to investigate the role of endothelin-1 (ET-1) in ventricular dilatation and the effects of chronic endothelin receptor blockade by a mixed ET <jats:sub>A</jats:sub> and ET <jats:sub>B</jats:sub> receptor blocker (bosentan) on the circulating and cardiac endothelin systems. </jats:p> <jats:p> <jats:italic>Methods and Results</jats:italic> Three hours after coronary ligation or sham operation, bosentan (100 mg · kg body wt <jats:sup>−1</jats:sup> · d <jats:sup>−1</jats:sup> ) or placebo was given by gavage. Seven days and 8 weeks after surgery, hemodynamic and left ventricular volume studies were performed. Acute bosentan treatment (7 days) had no effects on hemodynamic parameters and early left ventricular dilatation. In the rats with large infarcts, chronic bosentan treatment (8 weeks) versus placebo reduced left ventricular systolic pressure (116±2 versus 125±3 mm Hg, <jats:italic>P</jats:italic> &lt;.05) and arterial pressure (93±2 versus 103±3 mm Hg, <jats:italic>P</jats:italic> &lt;.05), improved stroke volume index (0.69±0.06 versus 0.52±0.04 mL/kg, <jats:italic>P</jats:italic> &lt;.05), and prevented in part the rightward shift of the pressure-volume curve. Chronic bosentan treatment also decreased ET-1 levels (390±33 versus 475±22 pg/g tissue, <jats:italic>P</jats:italic> &lt;.05) and density of ET-1 receptors (262±24 versus 346±31 fmol/mg protein, <jats:italic>P</jats:italic> &lt;.05) in left ventricular myocardium. </jats:p> <jats:p> <jats:italic>Conclusions</jats:italic> In the present study, a mixed ET <jats:sub>A</jats:sub> and ET <jats:sub>B</jats:sub> receptor antagonist (bosentan) partially prevented left ventricular dilatation and improved hemodynamics, suggesting that endothelin plays a role in left ventricular remodeling after myocardial infarction. Supporting this hypothesis, we show inhibitory effects of bosentan on the peripheral and myocardial endothelin system. </jats:p> Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling Circulation
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recordtype ai
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series Circulation
source_id 49
title_sub Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_unstemmed Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_full Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_fullStr Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_full_unstemmed Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_short Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_sort chronic endothelin receptor blockade attenuates progressive ventricular dilation and improves cardiac function in rats with myocardial infarction : possible involvement of myocardial endothelin system in ventricular remodeling
topic Physiology (medical)
Cardiology and Cardiovascular Medicine
url http://dx.doi.org/10.1161/01.cir.96.11.3963
publishDate 1997
physical 3963-3973
description <jats:p> <jats:italic>Background</jats:italic> Left ventricular dilatation after myocardial infarction is associated with impaired ventricular function and heart failure and has important implications for survival. The purpose of this study was to investigate the role of endothelin-1 (ET-1) in ventricular dilatation and the effects of chronic endothelin receptor blockade by a mixed ET <jats:sub>A</jats:sub> and ET <jats:sub>B</jats:sub> receptor blocker (bosentan) on the circulating and cardiac endothelin systems. </jats:p> <jats:p> <jats:italic>Methods and Results</jats:italic> Three hours after coronary ligation or sham operation, bosentan (100 mg · kg body wt <jats:sup>−1</jats:sup> · d <jats:sup>−1</jats:sup> ) or placebo was given by gavage. Seven days and 8 weeks after surgery, hemodynamic and left ventricular volume studies were performed. Acute bosentan treatment (7 days) had no effects on hemodynamic parameters and early left ventricular dilatation. In the rats with large infarcts, chronic bosentan treatment (8 weeks) versus placebo reduced left ventricular systolic pressure (116±2 versus 125±3 mm Hg, <jats:italic>P</jats:italic> &lt;.05) and arterial pressure (93±2 versus 103±3 mm Hg, <jats:italic>P</jats:italic> &lt;.05), improved stroke volume index (0.69±0.06 versus 0.52±0.04 mL/kg, <jats:italic>P</jats:italic> &lt;.05), and prevented in part the rightward shift of the pressure-volume curve. Chronic bosentan treatment also decreased ET-1 levels (390±33 versus 475±22 pg/g tissue, <jats:italic>P</jats:italic> &lt;.05) and density of ET-1 receptors (262±24 versus 346±31 fmol/mg protein, <jats:italic>P</jats:italic> &lt;.05) in left ventricular myocardium. </jats:p> <jats:p> <jats:italic>Conclusions</jats:italic> In the present study, a mixed ET <jats:sub>A</jats:sub> and ET <jats:sub>B</jats:sub> receptor antagonist (bosentan) partially prevented left ventricular dilatation and improved hemodynamics, suggesting that endothelin plays a role in left ventricular remodeling after myocardial infarction. Supporting this hypothesis, we show inhibitory effects of bosentan on the peripheral and myocardial endothelin system. </jats:p>
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author Fraccarollo, Daniela, Hu, Kai, Galuppo, Paolo, Gaudron, Peter, Ertl, Georg
author_facet Fraccarollo, Daniela, Hu, Kai, Galuppo, Paolo, Gaudron, Peter, Ertl, Georg, Fraccarollo, Daniela, Hu, Kai, Galuppo, Paolo, Gaudron, Peter, Ertl, Georg
author_sort fraccarollo, daniela
container_issue 11
container_start_page 3963
container_title Circulation
container_volume 96
description <jats:p> <jats:italic>Background</jats:italic> Left ventricular dilatation after myocardial infarction is associated with impaired ventricular function and heart failure and has important implications for survival. The purpose of this study was to investigate the role of endothelin-1 (ET-1) in ventricular dilatation and the effects of chronic endothelin receptor blockade by a mixed ET <jats:sub>A</jats:sub> and ET <jats:sub>B</jats:sub> receptor blocker (bosentan) on the circulating and cardiac endothelin systems. </jats:p> <jats:p> <jats:italic>Methods and Results</jats:italic> Three hours after coronary ligation or sham operation, bosentan (100 mg · kg body wt <jats:sup>−1</jats:sup> · d <jats:sup>−1</jats:sup> ) or placebo was given by gavage. Seven days and 8 weeks after surgery, hemodynamic and left ventricular volume studies were performed. Acute bosentan treatment (7 days) had no effects on hemodynamic parameters and early left ventricular dilatation. In the rats with large infarcts, chronic bosentan treatment (8 weeks) versus placebo reduced left ventricular systolic pressure (116±2 versus 125±3 mm Hg, <jats:italic>P</jats:italic> &lt;.05) and arterial pressure (93±2 versus 103±3 mm Hg, <jats:italic>P</jats:italic> &lt;.05), improved stroke volume index (0.69±0.06 versus 0.52±0.04 mL/kg, <jats:italic>P</jats:italic> &lt;.05), and prevented in part the rightward shift of the pressure-volume curve. Chronic bosentan treatment also decreased ET-1 levels (390±33 versus 475±22 pg/g tissue, <jats:italic>P</jats:italic> &lt;.05) and density of ET-1 receptors (262±24 versus 346±31 fmol/mg protein, <jats:italic>P</jats:italic> &lt;.05) in left ventricular myocardium. </jats:p> <jats:p> <jats:italic>Conclusions</jats:italic> In the present study, a mixed ET <jats:sub>A</jats:sub> and ET <jats:sub>B</jats:sub> receptor antagonist (bosentan) partially prevented left ventricular dilatation and improved hemodynamics, suggesting that endothelin plays a role in left ventricular remodeling after myocardial infarction. Supporting this hypothesis, we show inhibitory effects of bosentan on the peripheral and myocardial endothelin system. </jats:p>
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spelling Fraccarollo, Daniela Hu, Kai Galuppo, Paolo Gaudron, Peter Ertl, Georg 0009-7322 1524-4539 Ovid Technologies (Wolters Kluwer Health) Physiology (medical) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/01.cir.96.11.3963 <jats:p> <jats:italic>Background</jats:italic> Left ventricular dilatation after myocardial infarction is associated with impaired ventricular function and heart failure and has important implications for survival. The purpose of this study was to investigate the role of endothelin-1 (ET-1) in ventricular dilatation and the effects of chronic endothelin receptor blockade by a mixed ET <jats:sub>A</jats:sub> and ET <jats:sub>B</jats:sub> receptor blocker (bosentan) on the circulating and cardiac endothelin systems. </jats:p> <jats:p> <jats:italic>Methods and Results</jats:italic> Three hours after coronary ligation or sham operation, bosentan (100 mg · kg body wt <jats:sup>−1</jats:sup> · d <jats:sup>−1</jats:sup> ) or placebo was given by gavage. Seven days and 8 weeks after surgery, hemodynamic and left ventricular volume studies were performed. Acute bosentan treatment (7 days) had no effects on hemodynamic parameters and early left ventricular dilatation. In the rats with large infarcts, chronic bosentan treatment (8 weeks) versus placebo reduced left ventricular systolic pressure (116±2 versus 125±3 mm Hg, <jats:italic>P</jats:italic> &lt;.05) and arterial pressure (93±2 versus 103±3 mm Hg, <jats:italic>P</jats:italic> &lt;.05), improved stroke volume index (0.69±0.06 versus 0.52±0.04 mL/kg, <jats:italic>P</jats:italic> &lt;.05), and prevented in part the rightward shift of the pressure-volume curve. Chronic bosentan treatment also decreased ET-1 levels (390±33 versus 475±22 pg/g tissue, <jats:italic>P</jats:italic> &lt;.05) and density of ET-1 receptors (262±24 versus 346±31 fmol/mg protein, <jats:italic>P</jats:italic> &lt;.05) in left ventricular myocardium. </jats:p> <jats:p> <jats:italic>Conclusions</jats:italic> In the present study, a mixed ET <jats:sub>A</jats:sub> and ET <jats:sub>B</jats:sub> receptor antagonist (bosentan) partially prevented left ventricular dilatation and improved hemodynamics, suggesting that endothelin plays a role in left ventricular remodeling after myocardial infarction. Supporting this hypothesis, we show inhibitory effects of bosentan on the peripheral and myocardial endothelin system. </jats:p> Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling Circulation
spellingShingle Fraccarollo, Daniela, Hu, Kai, Galuppo, Paolo, Gaudron, Peter, Ertl, Georg, Circulation, Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling, Physiology (medical), Cardiology and Cardiovascular Medicine
title Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_full Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_fullStr Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_full_unstemmed Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_short Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_sort chronic endothelin receptor blockade attenuates progressive ventricular dilation and improves cardiac function in rats with myocardial infarction : possible involvement of myocardial endothelin system in ventricular remodeling
title_sub Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
title_unstemmed Chronic Endothelin Receptor Blockade Attenuates Progressive Ventricular Dilation and Improves Cardiac Function in Rats With Myocardial Infarction : Possible Involvement of Myocardial Endothelin System in Ventricular Remodeling
topic Physiology (medical), Cardiology and Cardiovascular Medicine
url http://dx.doi.org/10.1161/01.cir.96.11.3963