Experimental Study Of Catheter-based Transendocardial Injection Of Bone Marrow Stem Cells Into Ischemic Porcine Myocardium And Efficacy & Safety Of Paclitaxiel Slow Release Stents

BackgroundCoronary heart disease (CHD) has become more and more danger for human being. Because medical therapy can't get rid of the cause of CHD—coronary artery stenosis, coronary revascularization by percutaneous coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) has become common treatment options for patients with advanced ischemic heart disease. However, a significant number of patients (for example, patients with lesion of chronic total occlusion) are not candidates for standard revascularization procedures or have incomplete revascularization with these procedures. For these patients, stem cell transplantation therapy is thought to promote the angiogenesis or myogenesis.Drug-eluting stents have revolutionized the field of interventional cardiology. In discrete subsets of patients, there has been a dramatic decrease in clinical and angiographic restenosis. However, there is limited data in realworld patients. Paclitaxiel slow release stent, Taxus Express II have been used in our center from 2003. Many kind of lesion have been treated by taxus stent. We need to know exactly if it works effectively and safety.Aim1. We investigated whether catheter-based, intramyocardial transplantation of autologous bone marrow stem cells can enhance neovascularization in myocardial ischemia by dual-isotope (¹⁸F- FDG and ^99mTc-setamibi) imaging (DISA).2. To evaluate the efficacy and safety of taxus stent in real world. Record all of the MACE.3. To assess the effects of Taxus stents implantation on the platelet function in the coronary circulation.4. To assess the effects of Taxus stents implantation on the endothelium function.5. To evaluate the Effect on Endothelium Regeneration and Platelet Activation after Implantation of Taxus Stent.Methods1. Ten swine of 3⁴ months old,50⁶5kg were anaesthetized. Left anterior descending coronary artery were embolized by sterilized sponge. Bone marrow were aspirated from iliac crests of each swine, filtered, and gradient separated for mononuclear isolation. After plating cells in standard culture flasks and media, growth characteristics were quantified for both adherent and nonadherent populations over the first 48 hours. Nonadherent cells were removed and adherent cells maintained in continuous culture. Autologous transplantation of MSCs (MSC group,n=5), or PBS (Control group,n=5) was performed with a NOGA mapping injection catheter to target ischemic myocardium four weeks after myocardial infarction. Before and 4 weeks afterMSCs transplantation, each swine were examined by DISA, angiography and NOGA.2. 42 patients with coronary diseases underwent PTC A and stents implantation(21 of them TAXUS, and 21 of them BMS). Blood samples were obtained from the coronary sinus immediately before and 10min,6h after stent implantation. The plasma levels of GMP-140, TXB₂ were measured by radioimmunoassay.3. 42 patients with coronary diseases underwent PTC A and stents implantation(21 of them TAXUS, and 21 of them BMS). Blood samples were obtained from the femoral artery immediately before and 10min,6h,12h,24h after stent implantation. The plasma levels of GMP-140, TXB2 were measured by radioimmunoassay.4 . 32 patients with coronary diseases underwent PTC A and stents implantation(16 of them TAXUS, and 16 of them BMS). Blood samples were obtained from the femoral artery immediately before and 10min,l week after, 1 month after stent implantation. The plasma levels of GMP-140 and TXB2 were measured by radioimmunoassay.5. 10 dogs were implanted Taxus stent and Nir stent in the same artery. 4 weeks after implantation of stents, the target vessel were ablated after angiography and observed by scanning electron microscope and HE slides for optical microscope of 5dogs. Other 5 were observed 12 weeks after stent implantation.Results1. 55(76.4%) of 72 ischemic or infarct regions in MSC group showed by DISA were improved, however 11(16.2%) of 68 in control group were improved. LLS ( Linear Local Shortening) in MSC group increased significantly than in control group (P<0.05), no significant changes in UpV( Unipolar potential) and BpV(Bipolar potential) values were found compared with control group (P>0.05). Significant increase in CVIB(Cycle Variation of Integrated Backscatter ) was found compared with values before MSCs transplantation or with control group (P<0.05).2. 371 lesions in 326 patients were treated by taxus stents. All of the procedure were succeed immediately. 2 acute thrombosis occurred in-hospital, 1 of the 2 patients died. 1 sub-acute thrombosis occurred in-hospital. 1 sub-acute thrombosis occurred after leaved hospital. 268(82.2%) patients achieved 6 months follow-up, 21 MACE have been recorded. 167(51.2%) patients achieved 12 months follow-up, 3 new MACE have been recorded.3. In contrast with pre-stent, there was a significant increase of plasma levels of GMP-140, TXB2 and MPAR 10 min after stent implantation in both two groups (P<0.01). There was no difference between two groups at that time. 6h after stent implantation, plasma levels of GMP-140 and TXB₂ in Taxus Group was much higher than pre-stent and 10min after stent implantation(P<0.01) .At that time, there was no difference in BMS between 6h after stent implantation and pre-stent. plasma levels of GMP-140 and TXB2 in Taxus Group was much higher than BMS group (P<0.01) .4. In contrast with pre-stent, there was a significant increase of plasma levels of ET-1 6h after stent implantation in both two groups (P<0.05). There was no difference between two groups at that time. 12h after stent implantation, plasma levels of ET-1 in Taxus Group was much higher than pre-stent and 10min after stent implantation (P<0.05) .5. In contrast with pre-stent, there was a significant increase of plasma levels of AngII 6h ,12h after stent implantation in both two groups (P<0.05) . There was no difference between two groups.6. In contrast with pre-stent, there was a significant increase of plasma levels of GMP-140 and TXB2 10 min after stent implantation in both two groups(P<0.01) . There was no difference between two groups at that time. 1 week after stent implantation, plasma levels of GMP-140 and TXB₂ in Taxus Group was much higher than pre-stent implantation (P<0.01) . plasma levels of GMP-140 and TXB₂ in Taxus Group was much higher than BMS group(P<0.01) at that time. 1 month after stents implantation, there is no differencen in both two groups and pre-stent in plasma levels of GMP-140 and TXB₂ (P>0.05) .7. By Scanning electronic microscope, target vessel of Taxus stent were not intact covered with endothelium 4 weeks after stent implantation. Platelet activation were observed at that. Target vessel of Nir stent were intact covered with endothelium. Platelet activation were not observed. 12 weeks after stent implantation, both two groups have been intact covered by endouthelium. No platelet activation were observed.8. By QCA, late loss of Nir stent 12 weeks after stent implantation was much higher than Taxus stent (P<0.01) . Acreage of intima and media in taxus segment were much smaller than Nir stent segment 12 weeks after stent implantation, so did the ratio of intima/media (P<0.01) .Conclusion1. These outcomes encourage future clinical trials of catheter-based, intramyocardial transplantation of autologous MSCs in the setting of chronic myocardial ischemia.2. NOGA could be used to evaluate both the electronic and the mechanical cardie function.3. Taxus stent would be used in any type of lesion, and the efficacy and safety were approved by our real world study.4. Implantation of Taxus stent might activate the platelet function. And implantation of taxus stent might not result in much severe endothelium injury.