Objectives To prove up the angiogenetic mechanism and effect of CSWT in vivo and vitro experiments, also to evaluate the feasibility and efficiency of CSWT for CAD in China.
Methods 1) The HUVECs cell lines were performed by different level of shock wave energy (0, 0.03, 0.09, 0.18, 0.24 mj/mm2) in vitro. HUVECs proliferation and the changes in mRNA and protein of VEGF, IL-8, ICAM-1 were observed before and 24 hours after CSWT. 2) 30 domestic swine were performed micro-embolism in the distal of left anterior descending. Therapy group was performed CSWT on 1, 3, 5 days after AMI with low energy (0.09 mJ/mm2) at 200 shoots/spot for 12 spots. At 30 days, Serum eNOS, expression of eNOS and bFGF in borderline of infarction, VEGF mRNA, VEGF protein, mRNA of MMP1 and TIMP1, capillary density and collateral vessel Rentrop score, the morphology parameters about left ventricular volume, regional wall motion and global ventricular function were measured and evaluated. 3) 131 patients Before and at 30 days after CSWT, mononuclear cells were obtained from peripheral blood and EPCs were cultured in EGM-2-MV medium. Morphology and the number of colonies of EPCs were observed and the level of VEGF, IL-8, SDF-1 and MMP-9 was determined. The efficacy of CSWT was assessed by the CCS angina scale, NYHA class, SAQ scale, 6MWT, nitroglycerin dose and SPECT.
Results 1) The results from real-time PCR revealed the 0.09mJ/mm2 shock energy significantly promoted the HUVECs proliferation (P < 0.05), and also markedly increased the expression of VEGF, IL-8, ICAM-1(P < 0.001). 2) In CSWT group, expression of eNOS and bFGF in borderline infarction were obviously higher than control group (P<0.01); the expression of VEGF mRNA was significantly increased (P < 0.01). 3) The cultured EPCs and EPC-CFU number in vitro and circulating VEGF, IL-8 level were significantly increased (P<0.01) after CSWT. Whereas SDF-1and MMP-9 had no significant changes (P > 0.05). All patients in the study had not adverse effect. At 12 month after CSWT, patients experienced improvement in NYHA(P<0.001), CCS(P<0.001), SAQ(P = 0.021), 6MWT(P = 0.012) and dosage of nitroglycerin (P <0.001) compared to control group. LVEF(P = 0.001), LVEDD(P = 0.002), summed perfused score (P<0.001)and metabolic score (P = 0.028) were also improved in CSWT group. CSWT was independent factor for improved cardiac function, quality of life and echocardiography parameters.
Conclusions CSWT appears to promote the expression of VEGF and IL-8 protein, also stimulate the EPCs proliferation, significantly increase the number and function of EPCs. We provide scientific evidence of CSWT is a safe and effective non-invasive intervention for patients with CAD. Indications of CSWT in China are concluded, not only for refractory CAD, but also for those chronic pectoris which are reluctant or have no condition to undergo the invasive therapy. DSE combined with MPI, and SPECT is a preferable method to locate the viable ischaemic myocardial segments and guarantees the accuracy and effect of CSWT. A CSWT regimen of 1 month duration provided similar therapeutic efficacy compared to a regimen of 3 months duration. CSWT is proven effective for patients without CABG/PCI and patients whose medication treatments are no longer effective.
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