Background Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo （TXL）...Background Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo （TXL） treatment around the transplantation of mesenchymal stem cells （MSCs） can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction （AMI） and reperfusion. Methods Twenty-eight Chinese mini-pigs were divided into four groups including a control group （n=7）; group 2, administration of low-close TXL alone from the 3rd day prior to AMI to the 4th day post transplantation （n=-7）; group 3, MSCs alone （n=-7） and group 4, TXL ＋ MSCs （n=7）. AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs （3×10^7 cells/animal） were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline （1 week after transplantation） and endpoint （6 weeks after transplantation） by single photon emission computed tomography （SPECT） and magnetic resonance imaging （MRI）. Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. Results At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone （P〈0.0001）; the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone （P〈0.0001） and the peri-infarct zone （P〈0.0001）. MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group （P〈0.0001）. SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group （P〈0.0001）. TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase （SOD） significantly increased and malondialdehyde （MDA） decreased in groups 2 and 4 by the administration of TXL. Conclusions Our study demonstrates the following： （1） immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; （2） TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.展开更多
Background Our previous studies have demonstrated that Tongxinluo （TXL）, a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A （PKA）-dependent manner. Th...Background Our previous studies have demonstrated that Tongxinluo （TXL）, a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A （PKA）-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. Methods In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL （0.05 g/kg, gavaged one hour prior to ischemia）, and TXL ＋ H-89 （a PKA inhibitor, intravenously and continuously infused at 1.0 μg/kg per minute） groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein （p-CREB） （Ser133）, tumor necrosis factor a （TNF-a）, P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. Results TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% （P〈0.05）. TXL pretreatment increased the PKA activity and the expression of Ser133 p-CREB in the reflow and no-reflow myocardium （P 〈0.05）. TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-a and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. Conclusion PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.展开更多
Background Recent data have shown that sirolimus-eluting stents （SES） reduced not only the incidences of restenosis but also of target vessel revascularization （TVR）. CYPHER and FIREBIRD stents are both widely use...Background Recent data have shown that sirolimus-eluting stents （SES） reduced not only the incidences of restenosis but also of target vessel revascularization （TVR）. CYPHER and FIREBIRD stents are both widely used SES in China. However, comparative data concerning differences in long-term safety and efficacy regarding CYPHER and FIREBIRD stents in the Chinese population are still not available.展开更多
Background In response to the increasing concern with the safety of the drug-eluting stent （DES）, the present study aimed to evaluate the long-term safety and efficacy of DES used for a Chinese patient population. M...Background In response to the increasing concern with the safety of the drug-eluting stent （DES）, the present study aimed to evaluate the long-term safety and efficacy of DES used for a Chinese patient population. Methods All patients, who underwent an index elective percutaneous coronary intervention with an implantation of either DES or bare-metal stent （BMS） in a single institution from April 2004 to December 2006, were included in the analysis. A propensity-score matching technique was applied to adjust and to minimize the impact of confounding factors. Results Overall, there were 1465 patients （20.2%） who had undergone an implantation of only BMS, and 5769 patients （79.8%） of only DES. The propensity-score matching technique set up 1321 pairs of patients for analysis. There were no significant differences between the rates of stent thrombosis （definite and probable） of the two groups （1.06% vs 1.21%, P=0.8580）. Although rates of mortality and myocardial infarction （MI） during the 2-year follow-up period had not differed significantly, rates of death/MI （3.0% vs 4.5%, P=0.0263）, target-lesion revascularization （TLR, 3.2% vs 8.5, P=0.0001）, target-vessel revascularization （TVR, 5.8% vs 9.5%, P 〈0.0001） and any revascularization （10.0% vs 13.3%, P=0.0066） were significantly lower for the DES group than for the BMS group. Among the patients in whom devices were implanted for off-label indications, the propensity-score matched rates of stent thrombosis, mortality, MI, and death/MI were not significantly different, while rates of TLR, TVR and any revascularization were significantly lower for the DES group than for the BMS group. Conclusions During the 2 years of follow-up post stenting, DES use is associated with lower rates of death/MI, TLR, TVR and any revascularization, compared with BMS, in propensity-score matched Chinese patient populations. In the setting of off-label usage, DES use is also associated with similar advantages.展开更多
目的分析老年(≥65岁)无保护左主干冠状动脉病变(unprotected left main coronary disease,ULMCAD)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)的疗效。方法2004年1月至2015年12月,在阜外医院行ULMCAD-PCI治疗的患者...目的分析老年(≥65岁)无保护左主干冠状动脉病变(unprotected left main coronary disease,ULMCAD)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)的疗效。方法2004年1月至2015年12月,在阜外医院行ULMCAD-PCI治疗的患者3960例,其中1397例年龄≥65岁(老年组),2563例年龄<65岁(非老年组)。临床终点事件包括3年随访时主要不良心脏事件(major adverse cardiovascular event,MACE)、全因死亡、心肌梗死、再次血运重建的发生率。结果与非老年组相比,老年组患者的MACE(16.2%∶13.5%,P=0.002)、全因死亡(6.1%∶2.3%,P<0.0001)、心肌梗死(6.1%∶3.5%,P<0.0001)、再次血运重建(7.7%∶9.6%,P=0.04)明显升高。应用倾向性评分校正后,两组之间的MACE(危险比[HR]:1.16,95%可信区间[CI]:0.93~1.53,P=0.18)以及再次血运重建(HR:0.81,95%CI:0.61~1.06,P=0.13)无统计学差异。然而,全因死亡(HR:2.08,95%CI:1.35~3.22,P=0.0007)和心肌梗死(HR:1.73,95%CI:1.16~2.56,P=0.0056)在老年组患者中发生率更高。结论3年随访结果表明,老年无保护左主干冠状动脉疾病患者介入治疗的临床预后劣于非老年ULMCAD患者。展开更多
Background Available drug-eluting stents （DES） have achieved great success in reducing restenosis rates. Recently,investigators have demonstrated that the durable polymer carrier plays a significant role in DES-rela...Background Available drug-eluting stents （DES） have achieved great success in reducing restenosis rates. Recently,investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid （PLGA） polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease.Methods A prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients （TIVOLI group： 168 patients; ENDEAVOR group：156 patients） at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions （lesion length ≤40 mm,reference vessel diameter 2.25-4.00 mm）. The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years,including major adverse cardiac events （cardiac death,myocardial infarction, or target-lesion revascularization） and stent thrombosis.Results Angiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group （in-stent （0.25±0.33） mm vs. （0.57±0.55） mm, diff （95% CI）-0.23 （-0.32, -0.14）, P 〈0.0001; in-segment （0.25±-0.33） mm vs. （0.42±-0.55） mm, diff （95% CI） -0.13 （-0.23, -0.02）,P=0.0083）. The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group （P=0.0229）. Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization （4.2% vs. 9.6%, P=0.0495） at 2 years. The two-year major adverse cardiac events （MACE） rate was lower for the TIVOLI group, but not significantly different （6.6% vs. 10.9%, P=0.1630）.Conclusions TIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization （TLR） at 2 years.The MACE rate at 2 years was comparable in both groups.展开更多
基金This work was supported by the grants from the National Basic Research Program(973 Program)Ministry of Science and Technology,China(No.2005CB523303)
文摘Background Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo （TXL） treatment around the transplantation of mesenchymal stem cells （MSCs） can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction （AMI） and reperfusion. Methods Twenty-eight Chinese mini-pigs were divided into four groups including a control group （n=7）; group 2, administration of low-close TXL alone from the 3rd day prior to AMI to the 4th day post transplantation （n=-7）; group 3, MSCs alone （n=-7） and group 4, TXL ＋ MSCs （n=7）. AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs （3×10^7 cells/animal） were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline （1 week after transplantation） and endpoint （6 weeks after transplantation） by single photon emission computed tomography （SPECT） and magnetic resonance imaging （MRI）. Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. Results At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone （P〈0.0001）; the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone （P〈0.0001） and the peri-infarct zone （P〈0.0001）. MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group （P〈0.0001）. SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group （P〈0.0001）. TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase （SOD） significantly increased and malondialdehyde （MDA） decreased in groups 2 and 4 by the administration of TXL. Conclusions Our study demonstrates the following： （1） immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; （2） TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.
文摘Background Our previous studies have demonstrated that Tongxinluo （TXL）, a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A （PKA）-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. Methods In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL （0.05 g/kg, gavaged one hour prior to ischemia）, and TXL ＋ H-89 （a PKA inhibitor, intravenously and continuously infused at 1.0 μg/kg per minute） groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein （p-CREB） （Ser133）, tumor necrosis factor a （TNF-a）, P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. Results TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% （P〈0.05）. TXL pretreatment increased the PKA activity and the expression of Ser133 p-CREB in the reflow and no-reflow myocardium （P 〈0.05）. TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-a and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. Conclusion PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.
文摘Background Recent data have shown that sirolimus-eluting stents （SES） reduced not only the incidences of restenosis but also of target vessel revascularization （TVR）. CYPHER and FIREBIRD stents are both widely used SES in China. However, comparative data concerning differences in long-term safety and efficacy regarding CYPHER and FIREBIRD stents in the Chinese population are still not available.
文摘Background In response to the increasing concern with the safety of the drug-eluting stent （DES）, the present study aimed to evaluate the long-term safety and efficacy of DES used for a Chinese patient population. Methods All patients, who underwent an index elective percutaneous coronary intervention with an implantation of either DES or bare-metal stent （BMS） in a single institution from April 2004 to December 2006, were included in the analysis. A propensity-score matching technique was applied to adjust and to minimize the impact of confounding factors. Results Overall, there were 1465 patients （20.2%） who had undergone an implantation of only BMS, and 5769 patients （79.8%） of only DES. The propensity-score matching technique set up 1321 pairs of patients for analysis. There were no significant differences between the rates of stent thrombosis （definite and probable） of the two groups （1.06% vs 1.21%, P=0.8580）. Although rates of mortality and myocardial infarction （MI） during the 2-year follow-up period had not differed significantly, rates of death/MI （3.0% vs 4.5%, P=0.0263）, target-lesion revascularization （TLR, 3.2% vs 8.5, P=0.0001）, target-vessel revascularization （TVR, 5.8% vs 9.5%, P 〈0.0001） and any revascularization （10.0% vs 13.3%, P=0.0066） were significantly lower for the DES group than for the BMS group. Among the patients in whom devices were implanted for off-label indications, the propensity-score matched rates of stent thrombosis, mortality, MI, and death/MI were not significantly different, while rates of TLR, TVR and any revascularization were significantly lower for the DES group than for the BMS group. Conclusions During the 2 years of follow-up post stenting, DES use is associated with lower rates of death/MI, TLR, TVR and any revascularization, compared with BMS, in propensity-score matched Chinese patient populations. In the setting of off-label usage, DES use is also associated with similar advantages.
文摘目的分析老年(≥65岁)无保护左主干冠状动脉病变(unprotected left main coronary disease,ULMCAD)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)的疗效。方法2004年1月至2015年12月,在阜外医院行ULMCAD-PCI治疗的患者3960例,其中1397例年龄≥65岁(老年组),2563例年龄<65岁(非老年组)。临床终点事件包括3年随访时主要不良心脏事件(major adverse cardiovascular event,MACE)、全因死亡、心肌梗死、再次血运重建的发生率。结果与非老年组相比,老年组患者的MACE(16.2%∶13.5%,P=0.002)、全因死亡(6.1%∶2.3%,P<0.0001)、心肌梗死(6.1%∶3.5%,P<0.0001)、再次血运重建(7.7%∶9.6%,P=0.04)明显升高。应用倾向性评分校正后,两组之间的MACE(危险比[HR]:1.16,95%可信区间[CI]:0.93~1.53,P=0.18)以及再次血运重建(HR:0.81,95%CI:0.61~1.06,P=0.13)无统计学差异。然而,全因死亡(HR:2.08,95%CI:1.35~3.22,P=0.0007)和心肌梗死(HR:1.73,95%CI:1.16~2.56,P=0.0056)在老年组患者中发生率更高。结论3年随访结果表明,老年无保护左主干冠状动脉疾病患者介入治疗的临床预后劣于非老年ULMCAD患者。
文摘Background Available drug-eluting stents （DES） have achieved great success in reducing restenosis rates. Recently,investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid （PLGA） polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease.Methods A prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients （TIVOLI group： 168 patients; ENDEAVOR group：156 patients） at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions （lesion length ≤40 mm,reference vessel diameter 2.25-4.00 mm）. The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years,including major adverse cardiac events （cardiac death,myocardial infarction, or target-lesion revascularization） and stent thrombosis.Results Angiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group （in-stent （0.25±0.33） mm vs. （0.57±0.55） mm, diff （95% CI）-0.23 （-0.32, -0.14）, P 〈0.0001; in-segment （0.25±-0.33） mm vs. （0.42±-0.55） mm, diff （95% CI） -0.13 （-0.23, -0.02）,P=0.0083）. The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group （P=0.0229）. Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization （4.2% vs. 9.6%, P=0.0495） at 2 years. The two-year major adverse cardiac events （MACE） rate was lower for the TIVOLI group, but not significantly different （6.6% vs. 10.9%, P=0.1630）.Conclusions TIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization （TLR） at 2 years.The MACE rate at 2 years was comparable in both groups.
