Astragalus Granule Prevents Ca2+ Current Remodeling in Heart Failure by the Downregulation of CaMKII.

BACKGROUND: Astragalus was broadly used for treating heart failure (HF) and arrhythmias in East Asia for thousands of years. Astragalus granule (AG), extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca2+ current (ICa-L) in HF mice by the downregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). METHODS: HF mice were induced by thoracic aortic constriction (TAC). After 4 weeks of AG treatment, cardiac function and QT interval were evaluated. Single cardiac ventricular myocyte was then isolated and whole-cell patch clamp was used to record action potential (AP) and ICa-L. The expressions of L-type calcium channel alpha 1C subunit (Cav1.2), CaMKII, and phosphorylated protein kinase A (p-PKA) were examined by western blot. RESULTS: The failing heart manifested distinct electrical remodeling including prolonged repolarization time and altered ICa-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak ICa-L, accelerated ICa-L inactivation, and positive frequency-dependent ICa-L facilitation. In addition, AG treatment suppressed the overexpression of CaMKII, but not p-PKA, in the failing heart. CONCLUSION: AG treatment protected the failing heart against electrical remodeling and ICa-L remodeling by downregulating CaMKII.

The NHLBI-sponsored Consortium for preclinicAl assESsment of cARdioprotective therapies (CAESAR): a new paradigm for rigorous, accurate, and reproducible evaluation of putative infarct-sparing interventions in mice, rabbits, and pigs.

RATIONALE: Despite 4 decades of intense effort and substantial financial investment, the cardioprotection field has failed to deliver a single drug that effectively reduces myocardial infarct size in patients. A major reason is insufficient rigor and reproducibility in preclinical studies. OBJECTIVE: To develop a multicenter, randomized, controlled, clinical trial-like infrastructure to conduct rigorous and reproducible preclinical evaluation of cardioprotective therapies. METHODS AND RESULTS: With support from the National Heart, Lung, and Blood Institute, we established the Consortium for preclinicAl assESsment of cARdioprotective therapies (CAESAR), based on the principles of randomization, investigator blinding, a priori sample size determination and exclusion criteria, appropriate statistical analyses, and assessment of reproducibility. To validate CAESAR, we tested the ability of ischemic preconditioning to reduce infarct size in 3 species (at 2 sites/species): mice (n=22-25 per group), rabbits (n=11-12 per group), and pigs (n=13 per group). During this validation phase, (1) we established protocols that gave similar results between centers and confirmed that ischemic preconditioning significantly reduced infarct size in all species and (2) we successfully established a multicenter structure to support CAESAR's operations, including 2 surgical centers for each species, a Pathology Core (to assess infarct size), a Biomarker Core (to measure plasma cardiac troponin levels), and a Data Coordinating Center-all with the oversight of an external Protocol Review and Monitoring Committee. CONCLUSIONS: CAESAR is operational, generates reproducible results, can detect cardioprotection, and provides a mechanism for assessing potential infarct-sparing therapies with a level of rigor analogous to multicenter, randomized, controlled clinical trials. This is a revolutionary new approach to cardioprotection. Importantly, we provide state-of-the-art, detailed protocols ("CAESAR protocols") for measuring infarct size in mice, rabbits, and pigs in a manner that is rigorous, accurate, and reproducible.

[Effect of liangxue shengji recipe on incidence of post-percutaneous coronary intervention restenosis and adverse cardiovascular events].

OBJECTIVE: To observe the intervention effect of Liangxue Shengji Recipe (LSR) on incidence of post-percutaneous coronary intervention (post-PCI) restenosis and adverse cardiovascular events. METHODS: With a randomized, single-blinded methods adopted, 100 patients with coronary artery disease (CHD) and underwent stent implantation were randomized into two groups, the control group and the treated group, conventional Western treatment was administered to them all, but with LSR to patients in the treated group additionally. They were followed up for at least six months. The incidences of post-PCI restenosis and adverse events, including cardiogenic death, acute myocardial infarction, recurrent angina pectoris, severe heart failure, further intervention and coronary artery bypass grafting, were observed to estimate the effect of LSR. RESULTS: No statistically significant difference between the two groups was shown in terms of incidences of intra-stent restenosis, recurrent angina pectoris, estimator of restenosis and its cumulative risk, as well as in reducing the incidence of single adverse event, but did show statistically significant difference between groups in reducing the incidence of united cardiovascular event (P=0.032) and its cumulative risk (P=0.036). CONCLUSION: Administration of LSR in post-PCI stage could significantly reduce the probability and cumulative risk of united cardiovascular events, and the beneficial effect presents at about six months post-PCI.

[Constructing a Cox proportional hazard regression model of prognosis factors of acute myocardial infarction by retrospective cohort study].

OBJECTIVE: To study the effects of the potential factors, including Chinese herbal decoction, on the long-term prognosis of acute myocardial infarction (AMI). METHODS: Previous clinical data of 162 patients with AMI were collected, who were followed-up to observe the important events for prognosis, as death and cardio-cerebral episode, and the Cox proportional hazards regression model was used to assess the relative factors. RESULTS: The degree of cardiac function (by New York grading) increased 1 grade when age increased for 10 years, and the relative hazardous degree (RHD) raised to 1.983 and 3.169. After treatment with Chinese herbal decoction and angiotensin converting enzyme inhibitor (ACEI), the RHD could be reduced to 0.177 and 0.161 respectively. Taking the important cardio-cerebral events, including death, as the endpoint, when age increased for 10 years, the cardiac function would increase for 1 grade and RHD of endpoint events increased to 2.021 and 1.863, if patients had history of anterior infarction, arrhythmia and diabetes mellitus, it increased to 2.903, 2.588 and 4.039 respectively. Chinese decoction and ACEI treatment could reduce it to 0.093 and 0.141 respectively. CONCLUSION: Age, heart failure, anterior infarction, arrhythmia and diabetes mellitus are the hazardous factors of the long-term prognosis of AMI, Chinese herbal decoction and ACEI are the protective factors.