Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96‐Hour Survival in a Ventricular Fibrillation Rat Model
Background Myocardial dysfunction is a critical cause of post‐cardiac arrest hemodynamic instability and circulatory failure that may lead to early mortality after resuscitation. Trimetazidine is a metabolic agent that has been demonstrated to provide protective effects in myocardial ischemia. Howev...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-03-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.023378 |
| _version_ | 1797859000123916288 |
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| author | Jingru Li Yuantong Qi Jianjie Wang Chenxi Dai Bihua Chen Yongqin Li |
| author_facet | Jingru Li Yuantong Qi Jianjie Wang Chenxi Dai Bihua Chen Yongqin Li |
| author_sort | Jingru Li |
| collection | DOAJ |
| description | Background Myocardial dysfunction is a critical cause of post‐cardiac arrest hemodynamic instability and circulatory failure that may lead to early mortality after resuscitation. Trimetazidine is a metabolic agent that has been demonstrated to provide protective effects in myocardial ischemia. However, whether trimetazidine protects against postresuscitation myocardial dysfunction is unknown. Methods and Results Cardiopulmonary resuscitation was initiated after 8 minutes of untreated ventricular fibrillation in Sprague‐Dawley rats. Animals were randomized to 4 groups immediately after resuscitation (n=15/group): (1) normothermia control (NTC); (2) targeted temperature management; (3) trimetazidine‐normothermia; (4) trimetazidine‐targeted temperature management. TMZ was administered at a single dose of 10 mg/kg in rats with trimetazidine. The body temperature was maintained at 34.0°C for 2 hours and then rewarmed to 37.5°C in rats with targeted temperature management. Postresuscitation hemodynamics, 96‐hours survival, and pathological analysis were assessed. Heart tissues and blood samples of additional rats (n=6/group) undergoing the same experimental procedure were collected to measure myocardial injury, inflammation and oxidative stress‐related biomarkers with ELISA‐based quantification assays. Compared with normothermia control, tumor necrosis factor‐α, and cardiac troponin‐I were significantly reduced, whereas the left ventricular ejection fraction and 96‐hours survival rates were significantly improved in the 3 experimental groups. Furthermore, inflammation and oxidative stress‐related biomarkers together with collagen volume fraction were significantly decreased in rats undergoing postresuscitation interventions. Conclusions Trimetazidine significantly alleviates postresuscitation myocardial dysfunction and improves survival by decreasing oxidative stress and inflammation in a ventricular fibrillation rat model. A single dose of trimetazidine administrated immediately after resuscitation can effectively improve cardiac function, whether used alone or combined with targeted temperature management. |
| first_indexed | 2024-04-09T21:22:26Z |
| format | Article |
| id | doaj.art-252fa62148b94dd5889c2a2519d40cc9 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-09T21:22:26Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-252fa62148b94dd5889c2a2519d40cc92023-03-28T04:20:50ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-03-0111610.1161/JAHA.121.023378Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96‐Hour Survival in a Ventricular Fibrillation Rat ModelJingru Li0Yuantong Qi1Jianjie Wang2Chenxi Dai3Bihua Chen4Yongqin Li5Department of Biomedical Engineering and Imaging Medicine Army Medical University Chongqing ChinaDepartment of Pharmaceutics College of Pharmacy Army Medical University Chongqing ChinaDepartment of Biomedical Engineering and Imaging Medicine Army Medical University Chongqing ChinaDepartment of Biomedical Engineering and Imaging Medicine Army Medical University Chongqing ChinaDepartment of Biomedical Engineering and Imaging Medicine Army Medical University Chongqing ChinaDepartment of Biomedical Engineering and Imaging Medicine Army Medical University Chongqing ChinaBackground Myocardial dysfunction is a critical cause of post‐cardiac arrest hemodynamic instability and circulatory failure that may lead to early mortality after resuscitation. Trimetazidine is a metabolic agent that has been demonstrated to provide protective effects in myocardial ischemia. However, whether trimetazidine protects against postresuscitation myocardial dysfunction is unknown. Methods and Results Cardiopulmonary resuscitation was initiated after 8 minutes of untreated ventricular fibrillation in Sprague‐Dawley rats. Animals were randomized to 4 groups immediately after resuscitation (n=15/group): (1) normothermia control (NTC); (2) targeted temperature management; (3) trimetazidine‐normothermia; (4) trimetazidine‐targeted temperature management. TMZ was administered at a single dose of 10 mg/kg in rats with trimetazidine. The body temperature was maintained at 34.0°C for 2 hours and then rewarmed to 37.5°C in rats with targeted temperature management. Postresuscitation hemodynamics, 96‐hours survival, and pathological analysis were assessed. Heart tissues and blood samples of additional rats (n=6/group) undergoing the same experimental procedure were collected to measure myocardial injury, inflammation and oxidative stress‐related biomarkers with ELISA‐based quantification assays. Compared with normothermia control, tumor necrosis factor‐α, and cardiac troponin‐I were significantly reduced, whereas the left ventricular ejection fraction and 96‐hours survival rates were significantly improved in the 3 experimental groups. Furthermore, inflammation and oxidative stress‐related biomarkers together with collagen volume fraction were significantly decreased in rats undergoing postresuscitation interventions. Conclusions Trimetazidine significantly alleviates postresuscitation myocardial dysfunction and improves survival by decreasing oxidative stress and inflammation in a ventricular fibrillation rat model. A single dose of trimetazidine administrated immediately after resuscitation can effectively improve cardiac function, whether used alone or combined with targeted temperature management.https://www.ahajournals.org/doi/10.1161/JAHA.121.023378cardiac arrestcardiopulmonary resuscitationmyocardial dysfunctionoxidative stresstargeted temperature managementtrimetazidine |
| spellingShingle | Jingru Li Yuantong Qi Jianjie Wang Chenxi Dai Bihua Chen Yongqin Li Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96‐Hour Survival in a Ventricular Fibrillation Rat Model Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiac arrest cardiopulmonary resuscitation myocardial dysfunction oxidative stress targeted temperature management trimetazidine |
| title | Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96‐Hour Survival in a Ventricular Fibrillation Rat Model |
| title_full | Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96‐Hour Survival in a Ventricular Fibrillation Rat Model |
| title_fullStr | Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96‐Hour Survival in a Ventricular Fibrillation Rat Model |
| title_full_unstemmed | Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96‐Hour Survival in a Ventricular Fibrillation Rat Model |
| title_short | Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96‐Hour Survival in a Ventricular Fibrillation Rat Model |
| title_sort | trimetazidine alleviates postresuscitation myocardial dysfunction and improves 96 hour survival in a ventricular fibrillation rat model |
| topic | cardiac arrest cardiopulmonary resuscitation myocardial dysfunction oxidative stress targeted temperature management trimetazidine |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.023378 |
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