| Part IPotential of Real-Time Myocardial Contrast Echocardiography Combined with Low Dose Dobutamine Stress in the Diagnosisof Coronary Artery DiseaseOBJECTIVES: We sought to test the potential of quantitative RT-MCE in the detection of CAD with the aid of pharmacologic stress, to explore the relationship between perfusion reserve and contractile reserve, and to assess the contribution of collateral blood flow (CBF).METHODS: 53 patients referred for coronary angiography underwent wall motion assessment, RT-MCE both at baseline and under low dose dobutamine stress. The images of RT-MCE were analyzed quantitatively from microbubble replenishment curves to assess myocardial perfusion and its reserve.RESULTS: At baseline, significant differences in β (0.29 ± 0.12; 0.26 ± 0.05; 0.21±0.03; 0.19 ± 0.03 respectively, p<0.01) and A× β (1.52 ± 0.58; 1.31±0.39; 1.09 ± 0.23; 0.95 ± 0.21 respectively p<0.01) were observed among four segments groups with graded coronary artery stenosis severity( < 30% stenosis; 30%-69% stenosis; 70%-89% stenosis; and beyond 90% stenosis), but not observed in parameter A; When under stress, significant differences in A(5.70±1.19; 5.49 ± 0.92; 5.39 ± 0.60; 5.06±0.71, respectively, p<0.01), β (0.66 ± 0.19; 0.54 ± 0.14; 0.37 ± 0.10; 0.28 ± 0.07, respectively, p<0.01) and A×β (3.71 ±1.28; 2.99 ± 0.92; 1.95 ± 0.53; 1.41±0.42, respectively, p<0.01) were observed among above mentioned groups; Graded decreasing in β reserve(2.51 ± 1.11; 2.20 ± 0.70; 1.80 ± 0.51; 1.51 ± 0.33,respectively, p<0.01) and A×β reserve(2.70±1.32; 2.41±0.85; 1.82 ± 0.50; 1.51±0.43, respectively, p<0.01)) could also be observed with increasing coronary stenosis severity. In five groups scored by WMS(1-5), concordance between contractile function and myocardial perfusion could be found both at rest (β: 0.26 ± 0.09; 0.23 ± 0.05; 0.20 ± 0.04; 0.18 ± 0.04; 0.16 ± 0.03, respectively, p<0.01; A×β: 1.37 ± 0.48; 1.13 ± 0.35; 1.01±0.23; 0.92 ± 0.23; 0.78 ± 0.20, respectively, p<0.01) and under stress(β: 0.54 ± 0.19; 0.35 ± 0.12; 0.26±0.07; 0.21±0.06; 0.15 ± 0.03, respectively, p<0.01; A×β: 2.96±1.24; 1.85 ± 0.81; 1.30 ± 0.37; 1.07 ± 0.35; 0.79 ± 0.24, respectively, p<0.01). This concordance is also valid in term of their reserves, the MCE parameters in segments with ameliorated contractile function is significantlyhigher than in those without. Furthermore, some significant differences in MCE parameters and WMS could be observed between segments with CBF and without.CONCLUSIONS: Quantitative RT-MCE in conjunction with dobutamine stress is feasible to identify and stratify CAD and to explore the perfusion-contractile correlation.Part IIAssessing Therapeutic Efficacy of Autologous Mononuclear Bone Marrow Cells Transplantation with RT-MCEin AMI PatientsOBJECTIVES: To evaluate the effectiveness of autologous mononuclear bone marrow cells transplantation (BMT) on wall motion score (WMS) after acute myocardial infarction (AMI); to assess the effectiveness of BMT on myocardial perfusion in infarct related areas with quantitative real-time myocardial contrast echocardiography (RT-MCE); ant to investigate the effect of BMT on myocardial perfusion reserves with RT-MCE in conjunction with low dose dobutamine stressing.METHODS: 21 patients with ST segment elevating acute anterior wall myocardial infarction were randomized into BMT group (n = 11) and control group (n = 10). Within 24 hour after the onset of AMI, the BMT group received autologous mononuclear bone marrow cells transplantation while the control group received bone marrow supernatant injection via intracoronary microcatheter placed in the criminal coronary 3 hours after successful percutaneous coronary intervention (PCI). Both groups received the optimal medication in the acute phase and in the follow-up period. Routine echocardiography and MCE were performed on each patient 1 week after treatment, and the routine echocardiography and MCE combined with low dose dobutamine stressing were performed in all patients 6 months later.RESULTS: Compared to 1 week after treatment, 35 of 90 segments in the left anterior descending artery (LAD) distributing territory showed amelioration in wall motion score in control group 6 months after treatment, while 56 of 99 segments inBMT group showed amelioration, a significant difference can be found between two groups (p = 0.02). As for the wall motion score index (WMSI) in the LAD distributing territory, it decreased by 0.40 ± 0.52 in control group and 0.60 ± 0.55 in BMT group after follow-up, a significant difference can also be found between two groups (p< 0.05). WMSI in both group became lower after low dose dobutamine stressing, but no significant difference could be observed between the changes of each group (0.29 ± 0.50 vs. 0.37 ± 0.51).No significant differences could be observed in MCE parameters A, β, and A×β between BMT group and control group in the LAD distributing territory 1 week after treatment, but significant difference in parameter β could be found between two groups 6 months after treatment (0.25 ± 0.03 vs. 0.24 ± 0.04, p<0.05); and the change of A×β in BMT group was significant greater than in control group after 6 months' follow-up (0.20 ± 0.24 vs. 0.08 ± 0.29, p<0.05) . Under low dose dobutamine stressing, parameter β and A×β of BMT group were significantly greater than those of control group (30 ± 0.16 vs. 0.36 ± 0.14, p<0.05; 1.56 ± 0.27 vs. 1.88 ± 0.88, p<0.05, respectively), in addition, the reserves of parameters A, β, and A×β of BMT group were significantly higher than those of control group (1.01 ±0.13 vs. 1.06 ± 0.13, p< 0.05; 1.22 ± 0.57 vs. 1.39 ± 0.50, p<0.05; 1.26 ± 0.68 vs. 1.51±0.67, p<0.05, respectively).In all the patients received autologous BMT, no adverse effect was observed in follow-up.CONCLUSIONS: Autologous BMT after successful PCI can improve myocardial contractibility, blood perfusion and perfusion reserve in ischemic areas than PCI alone, and it is of great safety; MCE study suggest that improving the myocardial blood perfusion in the infarct area maybe the mechanism of BMT to treat AMI.Part IIIAssessing Therapeutic Efficacy of Different Dosage G-CSFMobilized Bone Marrow Stem Cells Transplantation withRT-MCE in Chronic Ischemic Heart DiseaseOBJECTIVES: To evaluate the feasibility and therapeutic efficacy of different dosage granulocyte colony-stimulating factor (G-CSF) mobilized bone marrow stem cells transplantation in chronic ischemic heart disease by real-time myocardial contrast echocardiography.METHODS: We prospectively randomized 16 swines into four equal groups: control group, low dosage G-CSF group, normal dosage G-CSF group and high dosage G-CSF group. To establish chronic ischemic heart disease animal model, thoracotomy and pericardiectomy was performed and an artery constrictor was implanted around the left circumflex branch of coronary artery (LCX) in 16 swines. After total occlusion was confirmed by selective coronary angiography, saline was hypodermically injected for 5 days in control group, 2.5μg/kg/d G-CSF was hypodermically injected for 5 days in low dosage G-CSF group, 5μg/kg/d G-CSF for normal dosage G-CSF group and 10μg/kg/d G-CSF for high dosage G-CSF group likewise. Before and 4 weeks after the injection, routine echocardiography and real-time myocardial contrast echocardiography was examined on each animal model to measure global heart function such as left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs) and left ventricular ejection fraction (LVEF), segmental wall motion score and local myocardial perfusion in the LCX distributing territory.RESULTS: There were no statistical difference in changes of LVDd, LVDs and LVEF before and 4 weeks after treatment among groups. As for paired sample student test of global heart function before and after treatment intra-groups, LVDs was notably larger 4 weeks after treatment than before treatment in control group(22.5±3.36 vs. 20.6 ± 3.44, p<0.05), while LVEF was lower (69.5 ± 5.01 vs. 74.2 ± 5.10, P=0.053). No statistical differences was found in other groups. As for wall motion score in the LCX distributing territory, 3 of 12 segments in control group, but 9 of 12 segments in normal dosage G-CSF group ameliorated after treatment (p< 0.05). As for myocardial perfusion in the LCX distributing territory, changes of A value, change of β value and change of A× β value in normal dosage G-CSF groupwere significantly higher than that in control group (0.27 ± 0.51 vs. -0.09 ± 0.36, p< 0.05; 0.05 ± 0.03 vs. 0.01±0.03, p<0.05; 0.30 ± 0.21 vs. 0.03 ± 0.17, p<0.05, respectively). We also found that changes of β value and change of A×β value in normal dosage G-CSF group were significantly higher than that in low dosage G-CSF group (0.05 ± 0.03 vs. 0.01±0.04, p<0.05; 0.30 ± 0.21 vs. 0.06 ± 0.15, p<0.05, respectively ). When paired sample student test of local myocardial perfusion before and after treatment were performed within each group, no statistical differences were found in control group and low dosage G-CSF group, but β value and A × β value 4 weeks after treatment were significantly higher than before treatment in normal dosage G-CSF group (0.28 ± 0.04 vs. 0.23 ± 0.05, p<0.05; 1.36 ± 0.22 vs. 1.06 ± 0.30, p<0.05, respectively), and A×β value 4 weeks after treatment were significantly higher than before treatment in high dosage G-CSF group (1.32 ± 0.24 vs. 1.18 ± 0.28, p<0.05).CONCLUSION: G-CSF mobilized bone marrow stem cells transplantation has beneficial effect on global heart function, segmental wall motion and myocardial perfusion in chronic ischemic heart disease. Normal dosage G-CSF was recommended by our research while the efficacy of high dosage G-CSF need to be further studied.
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