Cardioprotective effect and mechanism of action of landiolol on the ischemic reperfused heart
Cardioprotective effect and mechanism of action of landiolol on the ischemic reperfused heart
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DOI：
10.1007/s00540-007-0558-2
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发表时间：
2007-11-01
影响因子：
2.8
通讯作者：
Namiki, Akiyoshi
中科院分区：
文献类型：
--
作者：
Kimura-Kurosawa, Saori;Kanaya, Noriaki;Namiki, Akiyoshi
目的。作者研究了超短效、高选择性的β1受体阻滞剂兰地洛尔的心脏保护作用，以及它在缺血再灌流心脏做功、抗氧化作用和肌浆网(SR)功能中的作用。采用停灌45min再灌流的方法，建立豚鼠离体心缺血再灌注模型。缺血前用兰地洛尔(20、100、500MU)处理心脏15min(LAN组)。在另一组实验中，在缺血前，用兰地洛尔处理心脏15分钟(WO组)。在其他心脏，测定再灌流后组织丙二醛的浓度。我们还检测了磷蛋白在Ser(16)和Thr(17)残基上的磷酸化情况，以评估SR的功能。再灌流90min后，无论心率如何，LAN-500MU组左心室内压(LVP)均明显恢复。而WO组LVP恢复的改善消失。局灶性脑缺血再灌注组大鼠脑组织丙二醛水平明显低于对照组。对照组再灌流后Ser(16)和Thr(17)残基的磷蛋白磷酸化水平显著升高。500 mU M的兰地洛尔抑制Ser(16)残基的磷酸化增加。本研究证明兰地洛尔具有抗脂质过氧化作用，并能抑制缺血再灌流心脏Ser(16)残基上磷蛋白磷酸化的增加。这些发现表明兰地洛尔可能通过抗氧化作用和/或在缺血期保护SR功能而具有抗缺血作用。
Purpose. The authors examined the cardioprotective effect of landiolol, an ultra short-acting, highly selective beta 1-blocker, and its role in cardiac work, antioxidative effect, and sarcoplasmic reticulum (SR) function in hearts subjected to ischemia-reperfusion.Methods. Isolated guinea pig hearts were subjected to ischemia-reperfusion by stopping the perfusion for 45 min and reperfusing. Before the ischemia, hearts were treated with landiolol (20, 100, or 500 mu M) for 15 min (LAN group). In another set of experiments, before ischemia, hearts were washed out for 15 min after treatment with landiolol (WO group). In other hearts, the tissue concentration of malondialdehyde was measured after reperfusion. We also examined the phosphorylation of phospholamban at Ser(16) and Thr(17) residues to evaluate the SR function.Results. After 90 min of reperfusion, left ventricular pressure (LVP) was restored significantly in the LAN-500 mu M group regardless of heart rate. However, the improvement in recovery in LVP disappeared in the WO group. The tissue malondialdehyde levels were decreased in the LAN group compared with those in the control group. In the control group, the phosphorylation of phospholamban at Ser(16) and Thr(17) residues was markedly increased after reperfusion. Landiolol at 500 mu M suppressed the increase of phosphorylation at Ser(16) residues.Conclusion. The present study demonstrated that landiolol had a lipid peroxidation-reducing effect and suppressed the increase in phospholamban phosphorylation at the Ser(16) residue in hearts subjected to ischemia-reperfusion. These findings indicate that landiolol may have an anti-ischemic effect, via an antioxidant effect and/or via preserving SR function during the ischemic period.