Therapeutic Ultrasound Increases Myocardial Blood Flow in Ischemic Myocardium and Cardiac Endothelial Cells: Results of In Vivo and In Vitro Experiments
Therapeutic Ultrasound Increases Myocardial Blood Flow in Ischemic Myocardium and Cardiac Endothelial Cells: Results of In Vivo and In Vitro Experiments
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DOI：
10.1016/j.echo.2019.05.012
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发表时间：
2019-09-01
影响因子：
6.5
通讯作者：
Kaul, Sanjiv
中科院分区：
文献类型：
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作者：
Mott, Brian;Ammi, Azzdine Y.;Kaul, Sanjiv
背景：在冠状动脉血栓模型中，即使溶栓无效，治疗性超声也能缩小梗死面积。本研究的目的是测试的假设，超声诱导的心脏保护是由血管内皮细胞，增加心肌血流量（MBF），也有直接的组织抢救effects.Methods：在体内和体外实验进行了介导的分子使用1.05 MHz的换能器。对于体内实验，研究了10只对照和10只经历左前降支冠状动脉闭塞的超声处理的狗。用心肌声学造影测量MBF。对于体外实验，将原代小鼠心脏内皮细胞在基线或氧-葡萄糖剥夺后暴露于超声，并测量内皮一氧化氮合酶磷酸化以及腺苷和类二十烷酸环氧二十碳三烯酸、二羟基二十碳三烯酸和羟基-二十碳四烯酸。在体内，与对照组相比，超声治疗导致侧支衍生边缘区的MBF（20 +/- 10 vs 10 +/- 8，P = 0.03）和壁增厚（3 +/- 3% vs 1 +/-0.4%，P = 0.01）更高。与对照组相比，超声治疗组动物左前降支冠状动脉床的心外膜MBF也倾向于较高（17 +/- 17 vs 5 +/- 4，P = 0.05）;然而，该区域的内膜MBF与对照组相似（13 +/- 14 vs 14 +/- 7）。在体外，与未刺激的细胞相比，超声使磷酸化内皮型一氧化氮合酶和腺苷增加（分别增加129 +/- 11%和286 +/-63%，P <0.01）。用环氧二十碳三烯酸获得了类似的结果。氧糖剥夺后，磷酸化内皮型一氧化氮合酶减少，并恢复与应用超声波。环氧二十碳三烯酸也有类似的变化。细胞活力下降与氧-葡萄糖剥夺和恢复到接近基线与ultrason.Conclusions：超声增加MBF在体内缺血组织。这种效应可能是由超声治疗期间过多的冠状血管扩张剂的释放介导的，这些扩张剂也具有直接的组织挽救效应。因此，治疗性超声具有治疗急性和慢性心肌缺血的潜力，而不依赖于其对血栓溶解的影响。
Background: Therapeutic ultrasound can reduce infarct size in a model of coronary thrombosis even when so-nothronnbolysis is ineffective. The aim of this study was to test the hypothesis that ultrasound-induced cardioprotection is mediated by molecules released from the vascular endothelium that increase myocardial blood flow (MBF) and also have direct tissue-salvaging effects.Methods: In vivo and in vitro experiments were performed using a 1.05-MHz transducer. For the in vivo experiments 10 control and 10 ultrasound-treated dogs undergoing occlusion of the left anterior descending coronary artery were studied. MBF was measured using myocardial contrast echocardiography. For the in vitro experiments, primary mouse cardiac endothelial cells were exposed to ultrasound at baseline or following oxygen-glucose deprivation and endothelial nitric oxide synthase phosphorylation as well as adenosine and the eicosanoids epoxyeicosatrienoic acids, dihydroxyeicosatrienoic acids, and hydroxyl-eicosatetraenoic acids were measured.Results: In vivo, ultrasound treatment caused higher MBF (20 +/- 10 vs 10 +/- 8, P = .03) and higher wall thickening (3 +/- 3% vs 1 +/- 0.4%, P = .01) in the collateral-derived border zone compared with control. Epicardial MBF in the left anterior descending coronary artery bed also tended to be higher (17 +/- 17 vs 5 +/- 4, P = .05) in ultrasound-treated versus control animals; however, endocardial MBF in this region was similar to that in controls (13 +/- 14 vs 14 +/- 7). In vitro, phosphorylated endothelial nitric oxide synthase and adenosine increased (by 129 +/- 11% and 286 +/- 63%, respectively, P < .01) with ultrasound compared with unstimulated cells. Similar results were obtained with epoxyeicosatrienoic acids. After oxygen-glucose deprivation, phosphorylated endothelial nitric oxide synthase decreased and was restored with application of ultrasound. Similar changes were noted with epoxyeicosatrienoic acids. Cell viability decreased with oxygen-glucose deprivation and returned to near baseline with ultrasound.Conclusions: Ultrasound increases MBF in ischemic tissue in vivo. This effect is likely mediated by the release of a plethora of coronary vasodilators during ultrasound treatment that also have direct tissue-salvaging effects. Therapeutic ultrasound, therefore, has potential for treatment of acute and chronic myocardial ischemia independent of its effect on thrombolysis.