Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker, on myocardial apoptosis in ischemia-reperfusion injury.
The effects of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker with alpha-/beta-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.
Liang
Jhy-Chong
JC
Department of Early Childhood Care and Education, Chin Min Institute of Technology, Miaoli County, Taiwan.
Chen
Hen-Rong
HR
Chiu
Chaw-Chi
CC
Liou
Shu-Fen
SF
Chen
Ing-Jun
IJ
Yeh
Jwu-Lai
JL
D000758:Anesthesia; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002316:Cardiotonic Agents; D003402:Creatine Kinase / Q000097:blood; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D053938:DNA Fragmentation; D004095:Dihydropyridines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020107:Troponin T / Q000097:blood
D000840:Anisoles; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D004095:Dihydropyridines; D020107:Troponin T; C500368:labedipinedilol A; D004247:DNA; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D002118:Calcium