Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

Superselective adrenal arterial embolization for idiopathic hyperaldosteronism: 12-month results from a proof-of-principle trial.

OBJECTIVES: This study aimed to assess the safety, blood pressure changes, and biochemical responses of superselective adrenal artery embolization (SAAE) in hypertensive patients with idiopathic hyperaldosteronism (IHA). BACKGROUND: SAAE is a minimally invasive procedure that has been used to successfully treat aldosterone-producing adenoma. However, its effect for patients with IHA is unevaluated. METHODS: A total of 41 hypertensive patients who were diagnosed with IHA and underwent SAAE at the Fuwai Hospital between December 2010 and June 2016 were prospectively enrolled. The blood pressure, antihypertensive medications, plasma aldosterone and potassium levels, and adverse events were assessed. The primary endpoint was the change in home blood pressure at 12 months, compared with baseline. RESULTS: SAAE was technically successful in 39 patients. Postoperatively, home and 24-hr mean blood pressures were reduced by 14/9 and 10/7 mmHg at 1 month, respectively, and by 13/7 and 11/7 mmHg at 12 months, respectively. The number of antihypertensive agents used reduced by 1.0 and 1.1 at 1 month and 12 months, respectively (all p < .001). Compared with baseline (524.0 pmol/L), the standing plasma aldosterone reduced to 293.4 pmol/L at 12 months (p < .001). Serum potassium increased from 3.0 to 4.1 mmol/L while the rate of potassium supplement and mineralocorticoid receptor antagonist use reduced from 87.1 and 89.7%, respectively, to 28.2 and 17.9%, respectively, at 12 months (all p < .001). There were no serious complications in the perioperative and 12-month follow-up periods. CONCLUSIONS: SAAE was effective and feasible for IHA treatment, without serious complications, therefore, maybe a potential treatment.

China Tongxinluo Study for myocardial protection in patients with Acute Myocardial Infarction (CTS-AMI): Rationale and design of a randomized, double-blind, placebo-controlled, multicenter clinical trial.

Acute ST-segment elevation myocardial infarction (STEMI) remains a serious life-threatening event. Despite coronary revascularization, patients might still suffer from poor outcomes caused by myocardial no-reflow and ischemic/reperfusion injury. Tongxinluo (TXL), a traditional Chinese medicine, has been preliminarily demonstrated to reduce myocardial no-reflow and ischemic/reperfusion injury. We further hypothesize that TXL treatment is also effective in reducing clinical end points for the patients with STEMI. METHODS AND RESULTS: The CTS-AMI trial is a prospective, randomized, double-blind, placebo-controlled, multicenter clinical study in China. An estimated 3,796 eligible patients with STEMI from about 120 centers are randomized 1:1 ratio to TXL or placebo groups. All enrolled patients are orally administrated a loading dose of 8 capsules of TXL or placebo together with dual antiplatelet agents on admission followed by 4 capsules 3 times a day until 12 months. The primary end point is 30-day major adverse cardiovascular and cerebrovascular events, a composite of cardiac death, myocardial reinfarction, emergency coronary revascularization, and stroke. Secondary end points include each component of the primary end point, 1-year major adverse cardiovascular and cerebrovascular events, and other efficacy and safety parameters. CONCLUSIONS: Results of CTS-AMI trial will determine the clinical efficacy and safety of traditional Chinese medicine TXL capsule in the treatment of STEMI patients in the reperfusion era.

I-CARE randomized clinical trial integrating depression and acute coronary syndrome care in low-resource hospitals in China: Design and rationale.

Depression and acute coronary syndromes (ACS) are both common public health challenges. Patients with ACS often develop depression, which in turn adversely affects prognosis. Low-cost, sustainable, and effective service models that integrate depression care into the management of ACS patients to reduce depression and improve ACS outcomes are critically needed. Integrating Depression Care in ACS patients in Low Resource Hospitals in China (I-CARE) is a multicenter, randomized controlled trial to evaluate the efficacy of an 11-month integrated care (IC) intervention compared to usual care (UC) in management of ACS patients. Four thousand inpatients will be recruited and then randomized in a 1:1 ratio to an IC intervention consisting of nurse-led risk factor management, group-based counseling supplemented by individual problem-solving therapy, and antidepressant medications as needed, or to UC. The primary outcomes are depression symptoms measured by the Patient Health Questionnaire-9 at 6 and 12 months. Secondary endpoints include anxiety measured by the Generalized Anxiety Disorder-7; quality of life measured by the EQ-5D at 6 and 12 months; and major adverse events including the combined end point of all-cause death, suicide attempts, nonfatal myocardial infarction, nonfatal stroke, and all-cause rehospitalization at yearly intervals for a median follow-up of 2 years. Analyses of the cost-effectiveness and cost-utility of IC also will be performed. I-CARE trial will be the largest study to test the effectiveness of an integrated care model on depression and cardiovascular outcomes among ACS patients in resource-limited clinical settings.

Effects of Traditional Chinese Medicine Shensong Yangxin Capsules on Heart Rhythm and Function in Congestive Heart Failure Patients with Frequent Ventricular Premature Complexes: A Randomized, Double-blind, Multicenter Clinical Trial.

BACKGROUND: Pharmacological therapy for congestive heart failure (CHF) with ventricular arrhythmia is limited. In the study, our aim was to evaluate the effects of Chinese traditional medicine Shensong Yangxin capsules (SSYX) on heart rhythm and function in CHF patients with frequent ventricular premature complexes (VPCs). METHODS: This double-blind, placebo-controlled, multicenter study randomized 465 CHF patients with frequent VPCs to the SSYX (n = 232) and placebo groups (n = 233) for 12 weeks of treatment. The primary endpoint was the VPCs monitored by a 24-h ambulatory electrocardiogram. The secondary endpoints included the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) classification, 6-min walking distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores, and composite cardiac events (CCEs). RESULTS: The clinical characteristics were similar at baseline. SSYX caused a significantly greater decline in the total number of VPCs than the placebo did (-2145 ± 2848 vs. -841 ± 3411, P < 0.05). The secondary endpoints of the LVEF, NYHA classification, NT-proBNP, 6MWD, and MLHFQ scores showed a greater improvements in the SSYX group than in the placebo group (ΔLVEF at 12th week: 4.75 ± 7.13 vs. 3.30 ± 6.53; NYHA improvement rate at the 8th and 12th week: 32.6% vs. 21.8%, 40.5% vs. 25.7%; mean level of NT-proBNP in patients with NT-proBNP ≥125 pg/ml at 12th week: -122 [Q1, Q3: -524, 0] vs. -75 [Q1, Q3: -245, 0]; Δ6MWD at 12th week: 35.1 ± 38.6 vs. 17.2 ± 45.6; ΔMLHFQ at the 4th, 8th, and 12th week: -4.24 ± 6.15 vs. -2.31 ± 6.96, -8.19 ± 8.41 vs. -3.25 ± 9.40, -10.60 ± 9.41 vs. -4.83 ± 11.23, all P < 0.05). CCEs were not different between the groups during the study period. CONCLUSIONS: In this 12-week pilot study, SSYX was demonstrated to have the benefits of VPCs suppression and cardiac function improvement with good compliance on a background of standard treatment for CHF. TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR-TRC-12002061 (http://www.chictr.org.cn/showproj.aspx?proj=7487) and Clinicaltrials.gov, NCT01612260 (https://clinicaltrials.gov/ct2/show/NCT01612260).

Treatment and outcomes of acute coronary syndromes in women: An analysis of a multicenter quality improvement Chinese study.

BACKGROUND: Variations in care and outcomes by sex in patients with acute coronary syndrome (ACS) have been reported worldwide. The aims of this study are to describe ACS management according to sex in China and the effects of a quality improvement program in Chinese male and female ACS patients. METHODS AND RESULTS: Clinical Pathways for Acute Coronary Syndromes - Phase 2 (CPACS-2) was a cluster randomized trial to test whether a clinical pathways-based intervention would improve ACS management in China. The study enrolled 15,141 hospitalized patients [4631 (30.6%) were women] from 75 hospitals throughout China between October 2007 and August 2010. The intervention included clinical pathway implementation and performance measurement using standardized indicators with 6 monthly audit-feedback cycles. Eight key performance indicators reflecting in hospital management of ACS were measured. After adjustment for differences in patient characteristics and comorbidities at presentation, women were significantly less likely to undergo coronary angiography when indicated (RR 0.88 [0.85 to 0.92], P<0.001), less likely to receive guideline recommended medical therapies at discharge (RR 0.94 [0.91 to 0.98], P=0.003) and more likely to be hospitalized for shorter (mean difference -0.42 [-0.73 to -0.12] days, P=0.007). However, in-hospital clinical outcomes did not differ by sex. There was no evidence of heterogeneity in the relative effects of the quality improvement initiative by sex. CONCLUSIONS: Sex disparities were apparent in some key quality of care indicators for patients with suspected with ACS presenting to hospitals in China. The beneficial effect of the quality improvement program was consistent in women and men. CLINICAL TRIAL REGISTRATION: http://www.anzctr.org.au/default.aspx. Unique identifier: ACTRN12609000491268.

The Efficacy and Safety of Wenxin Keli in Patients with Frequent Premature Ventricular Contractions: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial.

BACKGROUND: Premature ventricular contractions (PVCs) are common in the general population, and frequent PVCs may result in the poor quality of life or even the damage of cardiac function. We examined the efficacy and safety of a traditional Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a relatively large Chinese cohort. METHODS: We performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200 eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin Keli or the placebo for 4 weeks. The primary and secondary endpoint was the change of PVC numbers and PVC-related symptoms after a 4-week treatment compared with baseline, respectively. In addition, vital signs, laboratory values, and electrocardiographic parameters were assessed in a safety analysis. RESULTS: At the initial evaluation, no significant differences in the baseline characteristics were observed between the Wenxin Keli group and the placebo group. A smaller number of PVCs was observed after the 4-week treatment than at baseline, in both the Wenxin Keli group (5686 ± 5940 vs. 15,138 ± 7597 beats/d, P < 0.001) and the placebo group (10,592 ± 8009 vs. 14,529 ± 5929 beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantli greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In a full analysis set, patients in the Wenxin Keli group exhibited significantly higher total effective responses in the reduction of PVCs compared to those in the placebo group (83.8% vs. 43.5%,P < 0.001). The per-protocol analysis yielded similar results (83.0% vs. 39.3%,P < 0.001). Treatment with Wenxin Keli also demonstrated superior performance compared to the placebo with respect to PVC-related symptoms. No severe adverse effects attributable to Wenxin Keli were reported. CONCLUSIONS: Wenxin Keli treatment effectively reduced the overall number of PVCs and alleviated PVC-related symptoms in patients without structural heart diseases and had no severe side effects.

[A cross-sectional study of factors related to traditional Chinese medicine use for hospitalized acute coronary syndrome patients in China's level 2 hospitals].

OBJECTIVE: To explore the current status on traditional Chinese medicine (TCM) use for hospitalized acute coronary syndrome patients in China's level 2 hospitals, and to explore associated factors of TCM use for these patients. METHODS: This survey was performed in 102 level 2 hospitals from 15 provinces or autonomous region in China. Patients admitted to these hospitals with acute coronary syndrome during September 2011 to May 2012 were eligible for this study. Information on TCM use was obtained from their medical records. Chi-square test and logistic regression analysis were used to explore the related factors of TCM use in these patients. RESULTS: We recruited 5 432 acute coronary syndrome patients in this study, TCM was applied to 3 503 patients (64.5%). Multivariable logistic regression showed that pre-hospital TCM use was positively related with in-hospital TCM use (OR = 2.08, P < 0.01) , while pre-hospital use of 4 medicines recommended by the guidelines(including aspirin/clopidogrel, ß acceptor blocker, stain and angiotensin converting enzyme inhibitor/angiotensin converting enzyme receptor blocker ), being a smoker and diagnosis of myocardial infarction rather than unstable angina at hospital discharge were negatively related with in-hospital TCM use (the ORs were 0.58, 0.78 and 0.71, respectively, all P < 0.01). The TCM use varied significantly between regions. Taking southwest region as a reference, the ORs varied between 2.98-13.37 (all P < 0.01) in eastern China, south China, central China, north China, northwest and northeast regions. CONCLUSIONS: TCM is widely used in hospitalized acute coronary syndrome patients in China's resource-constrained level 2 hospitals. Pre-hospital TCM use is positively correlated with in-hospital TCM use for these patients.

A multicenter, randomized, double-blind, parallel-group, placebo-controlled study of the effects of qili qiangxin capsules in patients with chronic heart failure.

OBJECTIVES: The purpose of this study was to assess the effects of qili qiangxin capsules in patients with chronic heart failure (CHF). BACKGROUND: Qili qiangxin capsules are a traditional Chinese medicine that has been approved in China for the treatment of CHF, but the evidence supporting its efficacy remains unclear. METHODS: A total of 512 patients with CHF were enrolled and randomly assigned to receive the placebo or qili qiangxin capsules in addition to their standard medications for the treatment of CHF. The primary endpoint was the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level during 12 weeks of treatment. RESULTS: At the 12-week follow-up, a significant reduction in the NT-proBNP level from baseline was observed in both groups, but the qili qiangxin capsule group demonstrated a significantly greater reduction than the placebo group (p = 0.002); 47.95% of patients in the qili qiangxin capsule group demonstrated reductions in NT-proBNP levels of at least 30% compared with 31.98% of patients in the placebo group (p < 0.001). Treatment with qili qiangxin capsules also demonstrated superior performance in comparison to the placebo with respect to New York Heart Association functional classification, left ventricular ejection fraction, 6-min walking distance, and quality of life. CONCLUSIONS: On a background of standard treatment, qili qiangxin capsules further reduced the levels of NT-proBNP. Together, our data suggest that qili qiangxin capsules could be used in combination therapy for CHF.

Prevalence, awareness, treatment, and control of hypertension in China: data from the China National Nutrition and Health Survey 2002.

BACKGROUND: The present article aims to provide accurate estimates of the prevalence, awareness, treatment, and control of hypertension in adults in China. METHODS AND RESULTS: Data were obtained from sphygmomanometer measurements and an administered questionnaire from 141 892 Chinese adults >/=18 years of age who participated in the 2002 China National Nutrition and Health Survey. In 2002, approximately 153 million Chinese adults were hypertensive. The prevalence was higher among men than women (20% versus 17%; P<0.001) and was higher in successive age groups. Overall, the prevalence of hypertension was higher in urban compared with rural areas in men (23% versus 18%; P<0.01) and women (18% versus 16%; P<0.001). Of the 24% affected individuals who were aware of their condition, 78% were treated and 19% were adequately controlled. Despite evidence to suggest improved levels of treatment in individuals with hypertension over the past decade, compared with estimates from 1991, the ratio of controlled to treated hypertension has remained largely unchanged at 1:4. CONCLUSIONS: One in 6 Chinese adults is hypertensive, but only one quarter are aware of their condition. Despite increased rates of blood pressure-lowering treatment, few have their hypertension effectively controlled. National hypertension programs must focus on improving awareness in the wider community, as well as treatment and control, to prevent many tens of thousands of cardiovascular-related deaths.

Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts.

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-dose 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 x 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.

[Seven core principles for treatment of hypertension].

The seven core principles (SeCP) for treatment of hypertension were (1) early identification, early diagnosis, early and life-long treatment; (2) application of long-acting and slow-released anti-hypertension drugs to control blood pressure smoothly; (3) use low dosage and combined therapy; (4) individual and racial therapy; (5) integrated traditional Chinese and Western medicine; (6) life style improvement; (7) enhancing compliance. Being more comprehensive and detailed than the Seventh Report of the Joint National Committee (JNC-7), the 2003' European Society of Hypertension/European Society of Cardiology (ESH/ESC2003), the report of the fourth working party of the British Hypertension Society (2004-BHS IV), and the 2004' Chinese Guideline of Hypertension (CGH2004), the programmatic SeCP should be promoted in clinical practice for hypertension patients and doctors to follow and apply.

[Effect of tongxinluo on endothelin-1 in the mini-swine model of acute myocardial infarction and reperfusion].

OBJECTIVE: To evaluate the change of endothelin-1 (ET-1) in the mini-swine model of acute myocardial infarction (AMI) and reperfusion and the effect of Tongxinluo (TXL) on it, and to explore the possible mechanism of no-reflow. METHODS: Forty mini-swines were randomized into 5 groups: the model group, the small,middle and large dose of TXL groups and the sham-operated group, 8 in each group. The AMI reperfusion model was established by coronary ligation for 3 hrs followed with relaxation for 1 hr. Plasma ET-1 content before and after AMI, and after reperfusion was determined respectively by radioimmunoassay. The ET-1 mRNA expression in myocardial tissue of normal, ischemic and no-reflow area were respectively quantified by reverse transcription-polymerase chain reaction. RESULTS: (1) Compared with before AMI, levels of plasma ET-1 at the time points of 5 min and 3 hrs after AMI, 5 min and 1 hrs after reperfusion in the model group were significantly raised, showing an increasing tendency (all P < 0.01). But the increment in the middle and large dose of TXL groups were all lower than that in the model group (P < 0.05). (2) In the model and the TXL groups, levels of ET-1 in myocardial tissue of ischemic and no-reflow area were significantly higher than those in the normal area, and the increment in no-reflow area was higher than that in ischemic area (all P < 0.01). Compared with the model group, significant lowering of ET-1 in ischemic area was only shown in the middle and large dose of TXL groups (P < 0.01). (3) In the model and the TXL groups, ET-1 mRNA expression in ischemic area was significantly higher (all P < 0.01), while it in no-reflow area was significantly lower than that in the normal area respectively (all P < 0.01). The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group (P < 0.01). CONCLUSION: The endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells. was significantly higher (all P < 0.01), while it in no-reflow area was significantly lower than that in the normal area respectively (all P < 0.01). The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group (P < 0.01). Conclusion The endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells.

[Clinical study on spontaneous improvement after blood flow reconstruction interfered by tongxinluo capsule in patients with early stage acute myocardial infarction].

OBJECTIVE: To observe and evaluate the effect of tongxinluo capsule (TXL) on recovery of ventricular wall with segmental dyskinesia in patients with early stage acute myocardial infarction (AMI). METHODS: One hundred and twelve AMI patients after percutaneous coronary intervention (PCI) or fibrinolytic therapy, were randomly divided into 2 groups, the control group (CG) treated with conventional medicine and the interfered group (IG) treated with conventional medicine plus TXL. The changes of ventricular wall motion, left ventricular end diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were observed at different time points (1-w, 2-w, 1-m, 3-m and 6-m) after PCI by using two dimensional echocardiography (2DE). RESULTS: The ventricular dyskinetic segment recovery rate at 1-w, 2-w, 1-m and 6-m in IG was 11.9%, 18.1%, 18.8% and 70.02% respectively, which was significantly higher than the respective rates in CG (4.1%, 8.3%, 11.1% and 51.68%, P < 0.01), but the 3-m recovery rate in the two groups was insignificantly different. LVEDV increase rate in the two groups at 1-w was insignificantly different, but it significantly increased at 2-w and 1-m, and showed a higher rate in CG (P < 0.05). However, at 3-m and 6-m, it significantly decreased in IG but was insignificantly changed in CG. Improvement of LVEF was insignificant at 1-w, 2-w and 1-m in both groups, but at 3-m and 6-m, LVEF was significantly improved in the interfered group (P < 0.01), but still showed no obvious change in the control group. CONCLUSION: Conventional western medicine combined with TXL can significantly decrease the infarction area, improve left ventricular diastolic function in patients with AMI.

[Beneficial effects of Tong-xin-luo (herb) on myocardial no-reflow after acute myocardial infarction and reperfusion: experiment of mini-swine model].

OBJECTIVE: To evaluate the beneficial effects of Tong-xin-luo on myocardial no-reflow after acute myocardial infarction (AMI) and reperfusion. METHODS: Forty mini-swine were randomized into 5 equal groups: control group, low-dose group (pretreated with Tong-xin-luo 0.05 g.kg(-1).d(-1) for 3 days), medium-dose group (pretreated with Tong-xin-luo 0.2 g .kg(-1).d(-1) for 3 days), high-dose group (pretreated with Tong-xin-luo 0.5 g.kg(-1).d(-1) for 3 days), and sham-operation group. The swine in the former four groups were subjected to 3 hours of coronary occlusion followed by 60 minutes of reperfusion. Left ventricle systolic pressure (LVSP), left ventricle end diastolic pressure (LVEDP), rate of maximum pressure change in left ventricle (+/- dp/dt(max)), cardiac output (CO), and heart rate (HR) were measured 5 min before AMI in all groups and 180 min after AMI and 60 min after reperfusion in the groups 1-4. Coronary blood volume (CBV) was recorded 5 min before AMI in all groups and immediately and 60 min after reperfusion in the group 1-4. Myocardial contrast echography (MCE) was used before AMI, 3 h after AMI, and 60 min after reperfusion in the group 1-4 so as to calculate the left ventricle wall area (LVWA), ligation area (LS), and %LA. Sixty minutes after reperfusion thioflavin-S was injected into the left ventricle to dye the reperfusion area, then the descending anterior branch was re-ligated at the original site and Evan's blue was injected into the left ventricle to dye the area outside the reperfusion area blue. The heart was taken out immediately to undergo pathological examination and calculation of LVWA, LS, area of no-reflow (SNR), LA, ANR. necrosis area (NS), and NA. RESULTS: (1) In the control group, systolic and diastolic blood pressures (SBP and DBP), LVSP, +/- dp/dt(max), and CO significantly decreased (P < 0.05 or P < 0.01), while LVEDP significantly increased (P < 0.01) 3 hour after AMI, and then LVSP was significantly recovered while +/- dp/dt(max) further significantly decreased (both P < 0.05) 60 minutes after reperfusion. In the 3 Tongxinluo groups, the changes of LVSP, +/- dp/dt(max), CO and LVEDP were the same as those in the control group 3 hours after AMI, and 60 minutes after reperfusion, +/- dp/dt(max), CO and LVEDP were recovered significantly in the high-dose group to degrees better than those in the control group (all P < 0.05). (2) In the control group, the LS values measured by MCE in vivo and by pathological evaluation were similar (P > 0.05), and the SNR was 78.5% by MCE in vivo and was 82.3% by pathological evaluation with the final NS reaching 98.5% of LS. There was no significant difference in LS by both MCE and pathological evaluation between the Tongxinluo groups and control group, though the values of SNR by both methods in the medium and high-dose groups were 41.1% and 42.4% and 24.1% and 25.0% respectively, all significantly lower than those in the control group and low-dose group (P < 0.05 or P < 0.01) with the values in the high-dose group being significantly lower than those in the median-dose group (P < 0.05 and P < 0.01). The final NS of pathological evaluation was also significantly decreased to 90.2%and 81.2% of LS (P < 0.05). In the control group, CBV was significantly decreased to 45.8% and 50.6% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.01). In the high-dose group, CBV was also significantly decreased to 76% and 73.5% of the baseline value immediately at the beginning of reperfusion and 60 minutes after reperfusion (both P < 0.05), however, both significantly higher than those in the control group (both P < 0.01). CONCLUSION: Tongxinluo is effective in preventing myocardial no-reflow, improving left ventricular function and reducing infarct area during AMI and reperfusion.

[The protective effects of Tong-xin-luo on myocardium and microvasculature after reperfusion in acute myocardial infarction].

OBJECTIVE: To evaluate the protective effects of Tongxinluo on myocardium and microvasculature after reperfusion in patients with acute myocardial infarction. METHODS: The research was performed on the patients with AMI whose initial ECG showed ST segment elevation and the patients received PCI or thrombolysis immediately after onset. These patients were classified randomly into two groups: control group in which the patients were given routine drug treatment (52 cases) and treatment group in which the patients were given routine drug plus Tongxinluo capsule (60 cases). We observed the abnormal movement of the ventricle wall in 2DE, and the change in LVEDV or LVEF on the 1st day, 7th day, 13th day, 3rd month, and 6th month after onset, which were compared with the result of DISA and SPECT for myocardial image. At the same time we also examined the blood NO and MDA levels on the 1st day, the 7th day and 13th day. RESULTS: (1) The recover rate for the abnormal movement of the ventricle segments in the treatment group were 11.86%, 18.12% and 18.79% respectively, which were higher than that of the control group (4.13%, 8.27% and 11.11% respectively) on the 1st week, the 2nd week, and the 1st month. At the 6th month the total recover rate for the abnormal movement of the ventricle segments of Tongxinluo group was 70.03%, which was significantly higher than that of the control group (51.68%). The WMSI was also decreased more than that of the control group. (2) The LVEDV in Tongxinluo group increased by 9.42% one week after onset, which was close to that of the control group (9.59%). There was no significant change (9.40% and 9.42% respectively) after two weeks and one month in Tongxinluo group, whereas it was increased continuously in the control group (11.84% and 12.33%). LVEDV in Tongxinluo group was decrease obviously after three and six months (3.62% and 5.07% respectively), which was close to the original level, whereas the result of the control group remained on a higher level (13.70% and 11.72% respectively). (3) LVEF of the Tongxinluo group was 53.32% before treatment, which was comparable with that of the control group (P = 0.45). There was no significant difference between the two groups after treatment for 1 week, 2 week and 1 month (P = 0.11, P = 0.13, P = 0.18, respectively). LVEF for the two groups was 58.27% and 53.40% respectively after three months and there was a statistical significance (P < 0.01). LVEF for the two groups was 58.33% and 53.82% respectively after 6 months and the difference remained statistically significant (P < 0.05). (4) The 2DE WMSI for the Tongxinluo group was 1.7552 after 12 hours to 24 hours of the CVR and there was no significant difference compared with that of the control group (WMSI = 1.5380, P = 0.6945). After 6 months, the WMSI decreased to 1.3767 in the Tongxinluo group, which was statistically different from that of the control group (WMSI = 1.5380, P < 0.01). The myocardium acquire isotope score index of the Tongxinluo group was 0.6075 at 6 months, which was significantly different from that of the control group (0.8781). (5) Ultrasonic humerus artery examination in static status showed that there was no significant difference on the diameter of blood vessel and the speed of blood stream between Tongxinluo group and control group with. The diameter of the blood vessel after artery pressure in Tongxinluo group was expanded, which was significantly different from that in the static status (P < 0.001) and that in control group (P < 0.001). The diameter of blood vessel after administration of nitroglycerin in both groups was expanded, which was significantly different from that in the static status (P < 0.001 and P < 0.05). However, Tongxinluo group was expand more obviously than that of the control group (P < 0.05). (6) The MDA level of the Tongxinluo group was decreased (all P < 0.05) and the NO level was increased (all P < 0.05) gradually from the 1st week to the 4th week; however, the MDA level of the control group was not decreased until the 4th week (P < 0.05), and the NO level of the control group was increased evidently at the 2nd week (P < 0.05). CONCLUSIONS: (1) After reperfusion in AMI patients, administration of routine drug combined with Tongxinluo is more effective than routine drug alone in the reduction of infarction size. (2) In Tongxinluo group, the recover time and the total recover rate of the abnormal movement of the ventricle segments were higher than the control group, and the WMSI were significantly decreased than the control group. (3) The improvement degree and the recover time on LVEDV in Tongxinluo group was superior to control group. (4) The improvement of LVEF in time and in degree was superior to control group. (5) The blood concentration of the MDA was decreased significantly in Tongxinluo group, while the NO level was increased significantly, and the time was superior to control group significantly.

Effects of xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term time course study in patients with stable angina.

BACKGROUND: Reduction of cholesterol and inflammation can be achieved by administration of a statin. Xuezhikang, an extract of cholestin, available from Chinese red yeast rice, could effectively modify the lipid profile. However, limited information is available regarding rapid effects of Xuezhikang on plasma C-reactive protein (CRP) and the lipid profile in patients with stable angina. We evaluated the short-term time course effects of lipid profile and CRP by Xuezhikang in patients with stable angina. METHODS: Forty-eight consecutive patients with stable angina were randomly assigned to 1200 or 2400 mg/day of Xuezhikang. Blood samples were drawn at days 0, 1, 7 and 14 for lipid profile and CRP levels in all patients, and hepatic enzymes were also evaluated at days 0 and 14. RESULTS: Both doses of Xuezhikang induced significant reductions in median CRP levels and in mean CRP levels at day 1 (13.0% with 1200 and 16.6% with 2400 mg/day; 14.7% with 1200 and 18.4% with 2400 mg/day), and at day 7 (18.3% with 1200 and 20.2% with 2400 mg/day; 18.5% with 1200 and 22.6% with 2400 mg/day) as well as at day 14 (28.6% with 1200 and 30.4% with 2400 mg/day; 21.7% with 1200 and 24.8% with 2400 mg/day) compared with baseline without a dose-dependent effect but a time-dependent manner. In addition, no changes were found at days 1 and 7 regarding lipid profile. However, both doses of Xuezhikang induced significant reductions in total cholesterol (TC, 13% and 22%), and low-density lipoprotein (LDL) cholesterol (23% and 32%) compared with baseline at day 14. The higher dose of Xuezhikang (2400 mg/day) resulted in significantly greater reductions in TC and LDL cholesterol compared with 1200 mg/day group (p<0.05, p<0.01, respectively). A less significant reduction was observed in triglycerides (TG) level (13% and 23%) compared with TC and LDL cholesterol. There was no significant difference in mean high-density lipoprotein (HDL) cholesterol levels compared with baseline in both groups. CONCLUSIONS: Xuezhikang resulted in rapid reduction of CRP within 24 h and lipid profile within 2 weeks, which may be clinically important for patients with coronary artery disease.

Comparative effects of carvedilol and losartan alone and in combination for preventing left ventricular remodeling after acute myocardial infarction in rats.

It has been verified that losartan has beneficial effects on ventricular remodeling (VRM) after acute myocardial infarction (AMI), but the effects of carvedilol alone or in combination with losartan on this condition have not been defined. The present study used rats to compare the effects of carvedilol and losartan alone and in combination for preventing VRM after AMI. After ligation of the left coronary artery, 100 surviving female Sprague-Dawley rats were randomly assigned to 1 of 4 groups: (1) AMI control (n=25), (2) carvedilol (Car, 1 mg x kg(-1) x day(-1)) (n=25), (3) losartan (Los, 3 mg x kg(-1) x day (-1)) (n=25), and (4) Car (1 mg x kg (-1). day(-1)) + Los (3 mg x kg(-1) x day (-1)) (n=25). A sham-operated group (n=17) was also randomly selected. Drugs were administered by gastric gavage for 4 weeks. After hemodynamic studies, the hearts were fixed and analyzed pathologically. Exclusive of the rats that had died or had an infarct size <35% or >55%, complete data were obtained for 65 rats, comprising AMI control (n=13), Car (n=12), Los (n=13), combination (n=14), and sham (n=13) groups. There were no significant differences in the size of infarct among the 4 AMI groups (45.8 approximately 46.7%, all p>0.05). Compared with the sham group, left ventricular (LV) end-diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all significantly increased (all p<0.001), whereas +/-dp/dt was significantly decreased (both p<0.001) in the AMI group. In comparison with the AMI group, LVEDP, LVV, LVW and STh were all significantly decreased (LVEDP: 12.7+/-2.3, 9.7+/-2.8, and 8.6+/-3.5 mmHg vs 20.6+/-2.7 mmHg, all p<0.001; LVV: 0.74+/-0.07, 0.76+/-0.07, and 0.70+/-0.09 ml vs 0.86+/-0.05 ml, all p<0.05; LVW: 668.4+/-52.0, 702.6+/-45.4, and 683.9+/-67.7 mg vs 787.3+/-76.7 mg, p<0.05 approximately 0.001; STh: 1.57+/-0.05, 1.48+/-0.07, and 1.46+/-0.07 mm vs 1.71+/-0.04 mm, all p<0.05), whereas +/-dp/dt was significantly increased (all p<0.05) in the Car, Los, and combination groups, with LVEDP decreasing more in both Los and the combination groups than in the Car group alone (p<0.05) and STh decreasing more in the combination group than in the Car group alone (p<0.05). Carvedilol and losartan alone and in combination all prevent VRM after AMI in rats, with almost equivalent effect.