Effect of Danhong Injection () on Improving Coronary Microcirculation Injury after Percutaneous Coronary Intervention.

OBJECTIVE: To explore the effectiveness of Danhong Injection () on improving microcirculatory injury after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). METHODS: A randomized controlled trial was conducted and 90 patients were enrolled. A random sequence was generated using statistical analysis software. Patients with microcirculatory injuries after PCI were randomly divided into 3 groups for treatment (30 subjects in each group): Danhong Injection group: after PCI, Danghong Injections were given with intravenous administration with 40 mL twice a day for a week; statins intensive group: after PCI, atorvastatin calcium tablets were given oral medication with 80 mg once, and then atorvastatin 40 mg daily for 1 week; the control group: after PCI, atorvastatin calcium tablets were given oral medication with 10-20 mg daily for 1 week. The index of microcirculation resistance (IMR) was used to assess microcirculatory injury during PCI. The IMR of the target vessel was reexamined after 1 week of drug treatment. RESULTS: After one week's drug treatment, IMR was significantly decreased in both statins intensive group and Danhong Injection group compared with the control group (P<0.01), but no difference was found between statins intensive group and Danhong injection group (14.03 ± 2.54 vs. 16.03 ± 5.72 U, P=0.080). CONCLUSIONS: The efficacy of Danhong Injection is non-inferior to statin. Early use of Danhong Injection after PCI can effectively improve coronary microcirculation injury after PCI.

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.

Oleanolic Acid, a Novel Endothelin A Receptor Antagonist, Alleviated High Glucose-Induced Cardiomyocytes Injury.

Endothelin-1 (ET-1) and its receptor endothelin A receptor (ET[Formula: see text] have been shown to be upregulated in a high glucose environment, which increase the incidence of diabetes-related heart failure. Our previous study demonstrated that oleanolic acid (OA), a natural compound found in Chinese herbs had ET-1 antagonistic effects. We aimed to verify whether OA could ameliorate diabetes mellitus (DM)-induced injury in cardiomyocytes by reducing the antagonistic effects of the ET-1 pathway. For the induction of high glucose-related injury in cardiomyocytes, neonatal rat ventricular cardiomyocytes (NRVMs) were subjected to culture medium containing 25[Formula: see text]mM of glucose. Natriuretic peptide B (BNP), mitochondrial membrane potential (MMP) and cell surface area were measured to evaluate the severity of NRVMs injury. mRNA expression of ET-1 and ETA was determined using quantitative PCR. Moreover, a Ca[Formula: see text] influx assay was used to evaluate potential ETA antagonistic effects. Molecular docking of OA and ETA was performed using the Sulflex-Dock program. Human induced pluripotent stem cell (iPS-C)-derived cardiomyocytes and real time cell analysis system (RTCA) were used to verify the effect of OA on the ET-1 pathway. High glucose levels increased the expression of BNP at both mRNA and protein levels in cardiomyocytes. Moreover, cell surface area and MMP were also elevated in a high glucose environment. High glucose-induced injury in NRVMs was not reversible by hypoglycemic therapy. In addition, ETA was upregulated by high glucose treatment and levels could not be reduced by hypoglycemic treatment. The Ca[Formula: see text] influx assay on ETA/HEK293 cells showed that OA had a partial ETA antagonistic effect. Molecular docking approaches showed that OA was docked into the active site of ETA. Furthermore, functionality tests based on iPS-C and RTCA demonstrated that treatment with OA could reverse ET-1-induced alternation of beating rates and amplitude. Thus, OA could reverse high glucose-induced BNP upregulation, and increased both the cell area and MMP in NRVMs. High glucose-induced irreversible ETA upregulation is a major reason of continuous diabetes-related injury in cardiomyocytes. Treatment with OA had a protective effect on high glucose-induced injury in cardiomyocytes through a partial ETA antagonistic role.