Yang Baofeng

Cardioprotective effects and underlying mechanisms of oxymatrine against Ischemic myocardial injuries of rats.

Oxymatrine has been demonstrated to have a variety of pharmacological actions. Accumulating evidence indicates that oxymatrine may exert a protective effect on the cardiovascular system. The study was designed to explore the possible role of oxymatrine against myocardial ischemic damage and several related signaling pathways as potential mechanisms. The protective properties of oxymatrine were studied in a rat model of acute myocardial infarction due to permanent ligation of the left anterior descending coronary artery. The results showed that administration of oxymatrine relieved myocardial injuries during ischemia, and this was achieved by protecting cardiomyocytes from apoptotic death. The beneficial effects of oxymatrine were likely mediated by an inhibition of lipid peroxidation (MDA production) and an increase in endogenous antioxidant activity (SOD), activation of the survival signaling molecule (Bcl‐2), and a reduction of apoptotic mediator (Fas) and intracellular Ca2+ overload. Copyright

Bone marrow mesenchymal stem cells upregulate transient outward potassium currents in postnatal rat ventricular myocytes.

Bone marrow mesenchymal stem cell (BMSC) transplantation has been shown to effectively improve cardiac function in experimental animals and patients with myocardial infarction and heart hypertrophy. BMSCs exert potent effects on cardiomyocytes through the inhibition of cardiac apoptosis, the attenuation of cardiac inflammation, etc. However, novel biological actions of BMSCs on cardiomyocytes remain to be explored. The present study was designed to investigate whether BMSCs affect electrophysiological features of neonatal rat ventricular myocytes (NRVMs). BMSCs and NRVMs were indirectly co-cultured at a ratio of 1:10 with a semi-permeable membrane. We found that compared with mono-cultured NRVMs, co-cultured NRVMs exhibited an obvious increase of transient outward potassium current (I(to)), accompanied by significant changes in activation, inactivation and recovery of I(to). Meanwhile, K(V)4.2 mRNA which encodes the channel carrying I(to) was more abundant in co-cultured NRVMs than mono-cultured NRVMs. The increases in basic fibroblast growth factor (bFGF) and insulin growth factor-1 (IGF-1) levels were observed in culture medium of BMSCs. bFGF but not IGF-1 upregulated the K(V)4.2 mRNA expression and enhanced I(to) currents. Taken together, we conclude that BMSCs upregulate I(to) of NRVMs, at least partially, by secreting bFGF that in turn upregulates K(V)4.2 expression and alters the kinetics of I(to).

A randomized, multicentre, open-label, parallel-group trial to compare the efficacy and safety profile of daming capsule in patients with hypercholesterolemia

To study the efficacy and tolerability of Daming capsule (DMC) in Chinese patients with hyperlipidemia, a randomized, multi‐centre, open‐label, parallel‐group trial was conducted. Sixty enrolled patients with hyperlipidemia allocated to six medical centers were randomly divided into two groups of 30 individuals each. One group received DMC 2 g b.i.d. for 6 weeks, and the other received pravastatin 10 mg o.d. for 6 weeks. For efficacy assessment, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL‐C) and high density lipoprotein cholesterol (HDL‐C) were measured before and after drug treatment. Serum TC and LDL‐C levels in the DMC‐treatment group were significantly decreased compared with those before treatment (p < 0.05), while TG and HDL‐C levels did not change much. Tolerability was assessed by heart rate (HR), blood pressure (BP), body mass index (BMI), alanine aminotransferase (ALT) and creatinine (Cr), which were not changed in either the DMC or pravastatin groups at 3 and 6 weeks (p > 0.05). Besides, eight patients experienced diarrhea during DMC treatment and two experienced myalgia and epigastric discomfort during pravastatin treatment. Based on the above results, it was concluded that DMC may be a good candidate for the treatment of hyperlipidemia and further clinical trials are warranted. Copyright

Ketamine-induced ventricular structural, sympathetic and electrophysiologic remodelling: pathological consequences and protective effects of metoprolol

Purpose Growing evidence suggested long-term abuse of ketamine did harm to the heart and increased the risk of sudden death. The present study was performed to explore the cardiotoxicity of ketamine and the protective effects of metoprolol. Methods Rats and rabbits were divided into control, ketamine poisoning and ketamine plus metoprolol groups. Ketamine (40 mg/kg/day, intraperitoneally) and metoprolol (20 mg/kg/day, orally) were administered continuously for 12 (rats) or eight (rabbits) weeks, respectively. Cardiac function and electrophysiological disturbances were examined, collagen volume fraction and apoptotic cell number were analysed and remodelling related proteins were detected by immunohistochemistry and western blot. Results Rabbits showed decreased left ventricular ejection fraction, slowed ventricular conduction velocity, and increased susceptibility to ventricular arrhythmia. Metoprolol prevented these pathophysiological alterations. In ketamine-treated rats, cardiac collagen volume fraction and apoptotic cell number were much higher than normal, which were mitigated by co-administration of metoprolol. Consistently, the expressions of poly (ADP-ribose) polymerases-1, apoptosis inducing factor and nuclear factor kappa-light-chain-enhancer of activated B cells were all increased after ketamine treatment, and sharply reduced after metoprolol administration. Moreover, ketamine enhanced sympathetic sprouting manifested by increased growth-associated protein 43 and tyrosine hydroxylase expression, which were also prevented by metoprolol. Conclusion Long-term abuse of ketamine caused significant ventricular myocardial apoptosis, fibrosis and sympathetic sprout, which altered the electrophysiologic property of the heart and increased the susceptibility to malignant arrhythmia that may lead to sudden cardiac death. Metoprolol prevented the cardiotoxicity of ketamine, representing a promising therapeutic strategy.