肾上腺髓质素在心肌缺血再灌注病人血浆中的变化及其对心肌的 …

目的　探讨肾上腺髓质素 (Adm)是否参与心肌缺血再灌注过程及其在此过程中的作用。方法　检测 17例急性心肌梗死 (AMI)接受静脉溶栓治疗血管再通的病人 ,溶栓 (再灌注 )前及溶栓 (再灌注 )后 4、12、2 4h ,3、7d及 2周时血浆肾上腺髓质素水平的动态变化 ,并在离体灌流大鼠心脏缺血再灌注模型上 ,观察再灌注过程中外源给予肾上腺髓质素对缺血再灌注损伤的影响。结果　AMI病人溶栓前血浆Adm水平为 3 8pmol/L± 0 8pmol/L明显高于正常对照 (1 9pmol/L± 0 .8pmol/L ,P <0 .0 1) ,溶栓治疗成功、心肌再灌注后进一步升高 ,溶栓后 4h血浆Adm水平达峰值 ,较溶栓前升高 42 .9% (P <0 .0 1) ,溶栓 12h后逐渐下降 ,2 4h降至溶栓前水平 ,2周时仍明显高于正常值。离体大鼠心脏灌流模型 ,缺血 45min后 ,用Adm(10 -7mol/L)再灌注 15min ,与单纯缺血再灌注组比较 ,可以使左心室内压收缩、舒张期最大变化率分别增加 76 .9%和 6 7.9% ,平均冠脉流量增加 48 8% ,灌流液中总蛋白 ,肌红蛋白含量和乳酸脱氢酶 (LDH)活性分别减少 34 .3%、6 3.6 %和 2 9.7%。结论　AMI病人溶栓后心肌再灌注时血浆Adm明显增加。Adm对离体大鼠心脏缺血再灌注损伤心肌具有保护作用。

Changes and cardiac protective effects of adrenomedullin during myocardial ischemia-reperfusion period

OBJECTIVE: To investigate if adrenomedullin (Adm) is concerned with cardiac ischemia-reperfusion (I/R) process and to study its effects on I/R injury. METHODS: Plasma Adm dynamic levels were tested in 17 patients with acute myocardial infarction (AMI), who had got successful blood reperfusion through intravenous thrombolytic therapy. The indices of I/R injury were measured in I/R models of isolated perfused rat heart when Adm (10(-7) mol/L) was given in reperfusion period. RESULTS: Plasma Adm concentrations before thrombolytic therapy in AMI patients were significantly higher than those of control group (3.8 pmol/L +/- 0.8 pmol/L vs 1.9 pmol/L +/- 0.8 pmol/L P < 0.01), and rose further after successful thrombolytic therapy, which resulted in efficient myocardial reperfusion. The peak level of plasma Adm, which appeared 4 hours after thrombolytic therapy, was 42.9% higher than that before therapy. The levels began to decrease and dropped to the levels before therapy at 12 and 24 hours after thrombolysis, respectively. In isolated perfused rat heart models, when Adm (10(-7) mol/L) was added in perfusion fluid for 15 minutes reperfusion after 45 minutes ischemic period, +/-LVdp/dt max of the heart increased 76.9% and 67.9%, and the average volume of coronary efflux increased 48.8%, respectively, compared with that of control group of ischemia-reperfusion. The amount of total protein, myoglobin and activities of LDH in effluent samples of Adm group were 34.3%, 63.6% and 29.2% lower than those of control group, respectively. CONCLUSION: Plasma Adm concentrations in AMI patients increase significantly during myocardiac reperfusion period after thrombolytic therapy. To some extent, Adm may have myocardial protective effects during ischemia-reperfusion period.