Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker, on myocardial apoptosis in ischemia-reperfusion injury

Jhy Chong Liang, Hen Rong Chen, Chaw Chi Chiu, Shu Fen Liou, Ing Jun Chen, Jwu Lai Yeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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 languageEnglish
Pages (from-to)1248-1256
Number of pages9
JournalLife Sciences
Volume79
Issue number13
DOIs
Publication statusPublished - 2006 Aug 22
Externally publishedYes

Keywords

  • Apoptosis
  • Calcium antagonist
  • Infarct
  • Ischemia-reperfusion

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry,Genetics and Molecular Biology

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