Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: molecular-cellular and functional assessment.

Extracorporeal shock wave therapy reverses ischemia-related left ventricular dysfunction and remodeling: molecular-cellular and functional assessment.
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DOI:
10.1371/journal.pone.0024342
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Yip HK
Yip HK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fu M;Sun CK;Lin YC;Wang CJ;Wu CJ;Ko SF;Chua S;Sheu JJ;Chiang CH;Shao PL;Leu S;Yip HK

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对于不适合导管或手术干预的弥漫性阻塞性动脉疾病患者的最佳治疗方法仍然悬而未决。本研究验证了体外冲击波(ECSW)治疗可能是这种临床情况下的治疗选择的假设。在雄性小型猪的左前降支(LAD)中段应用Ameroid缩窄器诱导心肌缺血。将12只小型猪平均随机分为第1组(仅LAD上的收缩肌)和第2组(手术后3个月,LAD上的收缩肌加ECSW [800个脉冲,0.09 mJ/mm 2]一次)。结果显示,在第0天和第90天,两组之间通过超声心动图测量的参数没有差异。然而,超声心动图和左心室(LV)血管造影显示,在第180天,组2的LV射血分数较高,LV收缩末期尺寸和体积较低(p<0.035)。CXCR 4和SDF-1α的mRNA和蛋白表达在实验2组均明显增加(p<0.04)。免疫荧光染色也显示组2中vWF-、CD 31-、SDF-1α-和CXCR 4-阳性细胞的数量更高(均p<0.04)。免疫组化染色显示,第2组的血管密度显著增加,但平均纤维化面积、CD 40阳性细胞数和凋亡细胞核数显著减少(均p<0.045)。第2组中氧化应激的线粒体蛋白表达较低,而细胞色素C较高(均p<0.03)。MMP-9、Bax和caspase-3 mRNA表达降低,Bcl-2、eNOS、VEGF和PGC-1α mRNA表达升高(均P<0.01)。总之,ECSW治疗有效地逆转缺血引起的左室功能障碍和重塑,通过增强血管生成和减轻炎症和氧化应激。
An optimal treatment for patients with diffuse obstructive arterial disease unsuitable for catheter-based or surgical intervention is still pending. This study tested the hypothesis that extracorporeal shock wave (ECSW) therapy may be a therapeutic alternative under such clinical situation. Myocardial ischemia was induced in male mini-pigs through applying an ameroid constrictor over mid-left anterior descending artery (LAD). Twelve mini-pigs were equally randomized into group 1 (Constrictor over LAD only) and group 2 (Constrictor over LAD plus ECSW [800 impulses at 0.09 mJ/mm2] once 3 months after the procedure). Results showed that the parameters measured by echocardiography did not differ between two groups on days 0 and 90. However, echocardiography and left ventricular (LV) angiography showed higher LV ejection fraction and lower LV end-systolic dimension and volume in group 2 on day 180 (p<0.035). Besides, mRNA and protein expressions of CXCR4 and SDF-1α were increased in group 2 (p<0.04). Immunofluorescence staining also showed higher number of vWF-, CD31-, SDF-1α-, and CXCR4-positive cells in group 2 (all p<0.04). Moreover, immunohistochemical staining showed notably higher vessel density but lower mean fibrosis area, number of CD40-positive cells and apoptotic nuclei in group 2 (all p<0.045). Mitochondrial protein expression of oxidative stress was lower, whereas cytochrome-C was higher in group 2 (all p<0.03). Furthermore, mRNA expressions of MMP-9, Bax and caspase-3 were lower, whereas Bcl-2, eNOS, VEGF and PGC-1α were higher in group 2 (all p<0.01). In conclusion, ECSW therapy effectively reversed ischemia-elicited LV dysfunction and remodeling through enhancing angiogenesis and attenuating inflammation and oxidative stress.
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发表时间: 2008-02-01
影响因子: 2.2
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发表时间: 1992-10-24
期刊: LANCET
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发表时间: 2007-08-01
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发表时间: 1978-01-01
期刊: CIRCULATION
影响因子: 37.8
作者:
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通讯作者: WEYMAN, A