Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction
Background-Insulin-like growth factor-1 (IGF-1) is recognized as an important regulator of cardiac structure and cardiomyocyte homeostasis. The prosurvival and antiapoptotic effects of IGF-1 have been investigated in vitro and in rodent models of myocardial infarction (MI). However, the clinical app...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
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2011
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| Online Access: | http://hdl.handle.net/20.500.11937/30558 |
| _version_ | 1848753122773565440 |
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| author | O'Sullivan, J. Leblond, A. Kelly, G. Kumar, A. Metharom, Pat Büneker, C. Alizadeh-Vikali, N. Hristova, I. Hynes, B. O'Connor, R. Caplice, N. |
| author_facet | O'Sullivan, J. Leblond, A. Kelly, G. Kumar, A. Metharom, Pat Büneker, C. Alizadeh-Vikali, N. Hristova, I. Hynes, B. O'Connor, R. Caplice, N. |
| author_sort | O'Sullivan, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Background-Insulin-like growth factor-1 (IGF-1) is recognized as an important regulator of cardiac structure and cardiomyocyte homeostasis. The prosurvival and antiapoptotic effects of IGF-1 have been investigated in vitro and in rodent models of myocardial infarction (MI). However, the clinical application of IGF-1 has been hampered by dose-dependent side effects both acutely and during chronic administration. We hypothesized that single, low-dose IGF-1 (LD-IGF-1) administered locally and early in the reperfusion phase after acute MI in a large animal model would avoid significant side effects but would have prosurvival effects that would manifest in long-term structural and functional improvement after MI treatment. Methods and Results-Forty-four female Landrace pigs underwent intracoronary administration of LD-IGF-1 or saline 2 hours into the reperfusion phase of acute left anterior descending artery occlusion MI. In the area of infarction, IGF-1 receptor and signaling responses were activated at 30 minutes and cardiomyocyte cell death attenuated at 24 hours after LD-IGF-1 but not saline treatment. Hemodynamic and structural studies using pressure-volume loop, CT, and triphenyltetrazolium chloride analysis 2 months post-MI confirmed a marked reduction in infarct size, attenuation of wall thinning, and augmentation of wall motion in the LD-IGF-1-treated but not in the saline-treated animals. These regional structural benefits were associated with global reductions in left ventricular volumes and significant improvement in left ventricular systolic and diastolic function. Conclusions-One-time LD-IGF-1 effects potent acute myocardial salvage in a preclinical model of left anterior descending artery occlusive MI, extending to long-term benefits in MI size, wall structure, and function and underscoring its potential as an adjunctive therapeutic agent. © 2011 American Heart Association, Inc. |
| first_indexed | 2025-11-14T08:19:30Z |
| format | Journal Article |
| id | curtin-20.500.11937-30558 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:19:30Z |
| publishDate | 2011 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-305582017-09-13T15:32:48Z Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction O'Sullivan, J. Leblond, A. Kelly, G. Kumar, A. Metharom, Pat Büneker, C. Alizadeh-Vikali, N. Hristova, I. Hynes, B. O'Connor, R. Caplice, N. Background-Insulin-like growth factor-1 (IGF-1) is recognized as an important regulator of cardiac structure and cardiomyocyte homeostasis. The prosurvival and antiapoptotic effects of IGF-1 have been investigated in vitro and in rodent models of myocardial infarction (MI). However, the clinical application of IGF-1 has been hampered by dose-dependent side effects both acutely and during chronic administration. We hypothesized that single, low-dose IGF-1 (LD-IGF-1) administered locally and early in the reperfusion phase after acute MI in a large animal model would avoid significant side effects but would have prosurvival effects that would manifest in long-term structural and functional improvement after MI treatment. Methods and Results-Forty-four female Landrace pigs underwent intracoronary administration of LD-IGF-1 or saline 2 hours into the reperfusion phase of acute left anterior descending artery occlusion MI. In the area of infarction, IGF-1 receptor and signaling responses were activated at 30 minutes and cardiomyocyte cell death attenuated at 24 hours after LD-IGF-1 but not saline treatment. Hemodynamic and structural studies using pressure-volume loop, CT, and triphenyltetrazolium chloride analysis 2 months post-MI confirmed a marked reduction in infarct size, attenuation of wall thinning, and augmentation of wall motion in the LD-IGF-1-treated but not in the saline-treated animals. These regional structural benefits were associated with global reductions in left ventricular volumes and significant improvement in left ventricular systolic and diastolic function. Conclusions-One-time LD-IGF-1 effects potent acute myocardial salvage in a preclinical model of left anterior descending artery occlusive MI, extending to long-term benefits in MI size, wall structure, and function and underscoring its potential as an adjunctive therapeutic agent. © 2011 American Heart Association, Inc. 2011 Journal Article http://hdl.handle.net/20.500.11937/30558 10.1161/CIRCINTERVENTIONS.110.960765 unknown |
| spellingShingle | O'Sullivan, J. Leblond, A. Kelly, G. Kumar, A. Metharom, Pat Büneker, C. Alizadeh-Vikali, N. Hristova, I. Hynes, B. O'Connor, R. Caplice, N. Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction |
| title | Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction |
| title_full | Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction |
| title_fullStr | Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction |
| title_full_unstemmed | Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction |
| title_short | Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction |
| title_sort | potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction |
| url | http://hdl.handle.net/20.500.11937/30558 |