Abstract | OBJECTIVE: In this study, experiments were designed to determine which parts and how carvedilol provided protection of the failed hearts under cardioplegia-induced hypoxia/reperfusion (H/R) insult. BACKGROUND:
Carvedilol could improve the perioperative and postoperative prognosis of the heart failure patients. The mechanism of carvedilol in prevention of the occurrence of cardiomyocytic apoptosis and preservation of cardiac function had been rarely studied. METHODS: Fifty Sprague-Dawley rats treated with placebo or daily carvedilol after coronary artery ligation were divided into five groups ( ligation only-group 2; ligation followed with cardioplegia- induced cardiac arrest-group 3; daily oral carvedilol treatment at 0.1, 1.0, or 10.0 mg/kg after ligation followed with cardioplegia- induced cardiac arrest-groups 4, 5, and 6), whereas another 10 animals received sham operation only (group 1), 30 days before ex vivo H/R injury. Failed hearts were harvested and received 1-h cardiac hypoxia with intermittent cold cardioplegia infusion and followed by 2-h reperfusion with warm oxygenated phosphate-buffered saline solution using a Langendorff apparatus. Perfusate was sampled at various time points. After H/R injury, the myocardium was carefully dissected into infarct, peri- infarct, and remote zones, which were used for further studies. In vitro H/R studies were carried on HL-1 cardiomyocytes to further explore the possible downstream pathways. RESULTS: CONCLUSIONS: In the failed heart, pretreatment with carvedilol could preserve cardiac contractility during cardioplegia-induced myocardial H/R injury by lessening inflammation-related genes and expression of cytokines, decreasing apoptosis-related proteins production and diminishing the occurrence of cardiomyocytic apoptosis in the peri- infarct zone. The cardinal pathways of the antiapoptotic mechanism of carvedilol were PI3K- and MEK-related pathways.
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Authors | Chi-Hsiao Yeh, Tzu-Ping Chen, Yao-Chang Wang, Yu-Min Lin, Shu-Wen Fang |
Journal | Shock (Augusta, Ga.)
(Shock)
Vol. 39
Issue 4
Pg. 343-52
(Apr 2013)
ISSN: 1540-0514 [Electronic] United States |
PMID | 23481492
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic beta-Antagonists
- Biomarkers
- Carbazoles
- Propanolamines
- Carvedilol
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Topics |
- Adrenergic beta-Antagonists
(pharmacology)
- Animals
- Apoptosis
(drug effects)
- Biomarkers
(metabolism)
- Carbazoles
(pharmacology)
- Carvedilol
- Dose-Response Relationship, Drug
- Flow Cytometry
- Heart Arrest, Induced
- Ligation
- Male
- Myocardial Infarction
(drug therapy, pathology)
- Myocardial Reperfusion Injury
(pathology, prevention & control)
- Myocytes, Cardiac
(pathology)
- Propanolamines
(pharmacology)
- Rats
- Rats, Sprague-Dawley
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