Lercanidipine对心肌病仓鼠心力衰竭过程中冠状反应和重构的作用

• 来源期刊: 中国药理学报（英文版）
• 学科: 医学
• 关键词: 钙通道阻滞药 心肌病 冠状血管 心力衰竭 lercanidipine 心肌
• 年，卷（期）: 2003,（3）
• 所属期刊栏目: 研究原著
• 页码范围: 199-206
• 页数: 8页
• 分类号: R9,R54
• 语种: 英文

摘要

AIM: Lercanidipine is a new vasoselective dihydropyridine calcium channel blocker with a short plasma half-life,long duration of action, and demonstrated cardioprotective properties. We hypothesized that it might be effective atattenuating the adverse impact observed on the coronary compartment and myocardium in the transition phase toheart failure in the UM-X7.1 cardiomyopathic (CM) hamster. METHODS: The effects of 4-month exposure tolercanidipine 3 and 10 mg/kg (daily oral administration) were evaluated in 150-day-old CM hamsters and in age-matched normal hamsters. Coronary reactivity (reactive hyperemia to 30-s coronary occlusion) and the responseto the administration of acetylcholine (100 nmol/L) and sodium nitroprusside (1 μmol/L) were assessed monthly,using the isolated perfused heart model. The left ventricular chamber dilatation index and wall thickness, myocar-dial fibrosis and myocardial capillary density (papillary muscle) were estimated in selected subgroups at monthlyintervals. RESULTS: High-dose lercanidipine had beneficial effects on coronary dysfunctions: at month 4 of thetreatment period, reactive hyperemia to short duration ischemia was improved, as was the endothelium-dependentvasodilator response (acetylcholine=68 %± 16 % vs 11%±5 % in untreated CM hamsters, P＜0.05)and endothe-lium-independent vasodilator response (sodium nitroprusside=36 %±5% vs 22 %± 12 % in untreated CM hamsters,P＜0.05). Capillary density averaged 10 879±474 capillaries per mm2in papillary muscle from normal hamsters; thisvalue did not change over time in normal hamsters and was not affected during the transition phase to heart failurein CM hamsters. Lercanidipine preserved myocardial capillary density in these conditions. Chronic exposure tolercanidipine had no impact on myocardial remodeling observed in CM hamsters. CONCLUSION: Lercanidipinehad a beneficial impact on the coronary compartment in the transition phase to heart failure in a model of dilatedcardiomyopathy.