Abstract
The effects of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker with α-/β-adrenoceptor blocking activities, on myocardial infarct size, apoptosis and necrosis in the rat after myocardial ischemia/reperfusion (45 min/120 min) were investigated. Ten minutes prior to left coronary artery occlusion, rats were treated with vehicle or labedipinedilol-A (0.25 or 0.5 mg/kg, i.v.). In the vehicle group, myocardial ischemia-reperfusion induced creatine kinase (CK) release and caused cardiomyocyte apoptosis, as evidenced by DNA ladder formation and terminal dUTP deoxynucleotidyltransferase nick end-labeling (TUNEL) staining. Treatment with labedipinedilol-A (0.25 or 0.5 mg/kg) reduced infarct size significantly compared to vehicle group (18.75 ± 0.65% and 8.27 ± 0.29% vs. 41.72 ± 0.73%, P < 0.01). Labedipinedilol-A also reduced the CK, CK-MB, lactate dehydrogenase (LDH) and troponin T levels in blood. In addition, labedipinedilol-A (0.5 mg/kg) significantly decreased TUNEL positive cells from 19.21 ± 0.52% to 9.73 ± 0.81% (P < 0.01), which is consistent with absence of DNA ladders in the labedipinedilol-A group. Moreover, labedipinedilol-A pretreatment also decreased calcium content in ischemic-reperfused myocardial tissue. In conclusion, these results demonstrate that labedipindielol-A, through reduction of calcium overload and apoptosis, exerts anti-infarct effect during myocardial ischemia-reperfusion and would be useful clinically in the prevention of acute myocardial infarction.
Original language | English |
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Pages (from-to) | 1248-1256 |
Number of pages | 9 |
Journal | Life Sciences |
Volume | 79 |
Issue number | 13 |
DOIs | |
Publication status | Published - 2006 Aug 22 |
Externally published | Yes |
Keywords
- Apoptosis
- Calcium antagonist
- Infarct
- Ischemia-reperfusion
ASJC Scopus subject areas
- General Pharmacology, Toxicology and Pharmaceutics
- General Biochemistry,Genetics and Molecular Biology