ReferenceID 4389
Cardioprotection by post-conditioning with exogenous triiodothyronine in isolated perfused rat hearts and isolated adult rat cardiomyocytes
Basic Res Cardiol
Ischemic post-conditioning (iPoCo) by coronary re-occlusion/reperfusion during immediate reperfusion after prolonged myocardial ischemia reduces infarct size. Mechanical manipulation of culprit lesions, however, carries
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Record Fields
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- Reference Id
- 4389
- Evidence Id
- 20979
- Core Evidence Id
- 20979
- Source Reference Id
- 2056
- Herb2 Reference Id
- HBREF002853
- Subject Paper Key
- HBIN007532_33876304
- Pubmed Id
- 33876304
- Doi
- 10.1007/s00395-021-00868-6
- Paper Title
- Cardioprotection by post-conditioning with exogenous triiodothyronine in isolated perfused rat hearts and isolated adult rat cardiomyocytes
- Paper Abstract
- Ischemic post-conditioning (iPoCo) by coronary re-occlusion/reperfusion during immediate reperfusion after prolonged myocardial ischemia reduces infarct size. Mechanical manipulation of culprit lesions, however, carries the risk of coronary microembolization which may obscure iPoCo's cardioprotection. Pharmacological post-conditioning with exogenous triiodothyronine (T3) could serve as an alternative conditioning strategy. Similar to iPoCo, T3 may activate cardioprotective prosurvival pathways. We aimed to study T3's impact on infarct size and its underlying signal transduction. Hearts were isolated from male Lewis rats (200-380 g), buffer-perfused and subjected to 30 min/120 min global zero-flow ischemia/reperfusion (I/R). In additional hearts, either iPoCo (2 x 30 s/30 s I/R) was performed or T3 (100-500 microg/L) infused at reperfusion. Infarct size was demarcated with triphenyl tetrazolium chloride staining and calculated as percent of ventricular mass. Infarct size was reduced with iPoCo to 16 +- 7% vs. 36 +- 4% with I/R only. The maximum infarct size reduction was observed with 300 microg/L T3 (14 +- 2%). T3 increased the phosphorylation of protein kinase B and mitogen extracellular-regulated-kinase 1/2, both key enzymes of the reperfusion injury salvage kinase (RISK) pathway. Pharmacological RISK blockade (RISK-BL) during reperfusion abrogated T3's cardioprotection (35 +- 10%). Adult ventricular cardiomyocytes were isolated from buffer-perfused rat hearts and exposed to 30 min/5 min hypoxia/reoxygenation (H/R); reoxygenation was initiated without or with T3, respectively, and without or with RISK-BL, respectively. Maximal preservation of viability was observed with 500 microg/L T3 after H/R (27 +- 4% of all cells vs. 5 +- 3% in time-matched controls). Again, RISK-BL abrogated protection (11 +- 3%). Mitochondria were isolated at early reperfusion from buffer-perfused rat hearts without or with iPoCo or 300 microg/L T3, respectively, at reperfusion. T3 improved mitochondrial function (i.e.: increased respiration, adenosine triphosphate production, calcium retention capacity, and decreased reactive oxygen species formation) to a similar extent as iPoCo. T3 at reperfusion reduces infarct size by activation of the RISK pathway. T3's protection is a cardiomyocyte phenomenon and targets mitochondria.
- Journal
- Basic Res Cardiol
- Publish Year
- 2021
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Ischemic Post-conditioning; Culprit Lesions; T3's; Coronary Microembolization
- Paper Title Cn
- Paper Title En
- Cardioprotection by post-conditioning with exogenous triiodothyronine in isolated perfused rat hearts and isolated adult rat cardiomyocytes
- Bilingual Status
- semi_complete