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

• Published in: Life sciences (1973) 2006-08, Vol.79 (13), p.1248-1256
• Main Authors: Liang, Jhy-Chong, Chen, Hen-Rong, Chiu, Chaw-Chi, Liou, Shu-Fen, Chen, Ing-Jun, Yeh, Jwu-Lai
• Format: Article
• Language: English
• Subjects: Anesthesia; Animals; Anisoles - pharmacology; Apoptosis; Apoptosis - drug effects; Calcium - metabolism; Calcium antagonist; Calcium Channel Blockers - pharmacology; Cardiotonic Agents; Creatine Kinase - blood; Dihydropyridines - pharmacology; DNA - biosynthesis; DNA - genetics; DNA Fragmentation; Hemodynamics - drug effects; In Situ Nick-End Labeling; Infarct; Ischemia–reperfusion; L-Lactate Dehydrogenase - blood; Male; Myocardial Infarction - pathology; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - pathology; Rats; Rats, Wistar; Troponin T - blood
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2006.03.033

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.