Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
PLoS One. 2011;6(9):e24342. doi: 10.1371/journal.pone.0024342. Epub 2011 Sep 6.
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/mm(2)] 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.
对于不适合经导管或手术干预的弥漫性阻塞性动脉疾病患者，仍需要寻找最佳治疗方法。本研究旨在验证这样一种假设，即体外冲击波（ESCW）治疗可能是这种临床情况下的一种治疗选择。通过在左前降支中段放置一种缩窄环来诱导雄性小型猪的心肌缺血。将 12 只小型猪等分为两组：组 1（仅在左前降支上放置缩窄环）和组 2（在左前降支上放置缩窄环并在术后 3 个月进行 ECSW[800 个脉冲，0.09 mJ/mm(2)]治疗）。结果显示，两组在第 0 天和第 90 天的超声心动图参数无差异。然而，在第 180 天，超声心动图和左心室（LV）造影显示组 2 的 LV 射血分数更高，LV 收缩末期直径和容积更小（p<0.035）。此外，组 2 的 CXCR4 和 SDF-1α 的 mRNA 和蛋白表达增加（p<0.04）。免疫荧光染色也显示，组 2 的 vWF-、CD31-、SDF-1α-和 CXCR4-阳性细胞数量更多（均 p<0.04）。此外，免疫组织化学染色显示，组 2 的血管密度明显更高，而平均纤维化面积、CD40 阳性细胞和凋亡核数量更小（均 p<0.045）。组 2 的氧化应激相关的线粒体蛋白表达降低，而细胞色素 C 表达升高（均 p<0.03）。此外，组 2 的 MMP-9、Bax 和 caspase-3 的 mRNA 表达降低，而 Bcl-2、eNOS、VEGF 和 PGC-1α 的 mRNA 表达升高（均 p<0.01）。综上所述，ESCW 治疗通过增强血管生成和减轻炎症和氧化应激，有效逆转缺血引起的 LV 功能障碍和重构。
