Antioxidant and lipid-regulating effects of probucol combined with atorvastatin in patients with acute coronary syndrome.

OBJECTIVE: To investigate the effects of probucol combined with atorvastatin on the serum oxidation index and lipid levels in patients diagnosed with acute coronary syndrome (ACS). METHODS: We randomly assigned 126 ACS patients (77 males and 49 females) to the control group (atorvastatin 20 mg/day, n=62) or the treatment group (atorvastatin 20 mg/day and probucol 750 mg/day, n=64). All the patients were followed up for 12 weeks. As oxidization indices, we measured the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), oxidized LDL (ox-LDL), and paraoxonase-1 (PON1) before and after treatment. We also monitored the adverse effects of the drugs during the treatment. RESULTS: At baseline, there were no obvious differences (P>0.05) between the two groups (including age, gender, etc.). After 12 weeks of treatment, the ox-LDL levels in the treatment group were significantly lower while PON1 levels were significantly higher than those in the control group. There were no statistically significant difference between the two groups with respect to the side effects (P<0.05). CONCLUSIONS: The combined use of atorvastatin and probucol in ACS patients could reduce ox-LDL expression and increase PON1 expression more effectively than use atorvastatin alone.

Association between cardiac changes and stress, and the effect of peroxisome proliferator-activated receptor-γ on stress-induced myocardial injury in mice.

This study was aimed to investigate the effect of stress induced by high-intensity exercises on the cardiovascular system. In the epidemiological investigation, 200 subjects (test group) engaged in special high-intensity exercises, and 97 who lived and worked in the same environment and conditions as those in the test group, but did not participate in the exercises served as controls. In the second part of the study, 50 mice were randomly divided into control group, exhaustive swimming group, white noise group, exhaustive swimming plus white noise group, and pioglitazone intervention group. The results showed that the plasma concentrations of the myocardial injury markers heart fatty acid-binding protein (H-FABP), C-reactive protein (CRP), ß-endorphin (ß-EP) and levels of psychological stress were significantly increased in test group as compared with control group; special high-intensity exercises resulted in a significant elevation of the incidence of cardiac arrhythmias. Animal experiments showed that the plasma levels of corticosterone (CORT) and troponin I (TnI) were raised while the level of SOD was reduced in exhaustive swimming group, white noise group, and exhaustive swimming plus white noise group. The expression levels of PPARγ mRNA and protein were decreased in myocardial tissues in these groups as well. HE staining showed no remarkable change in myocardial tissues in all the groups. Treatment with pioglitazone significantly decreased the plasma levels of TnI and CORT, while increased the level of SOD and the expression levels of PPARγ mRNA and protein. It was concluded that the high-intensity exercises may induce a heavy physical and psychological stress and predispose the subjects to accumulated fatigue and sleep deprivation; high-intensity exercises also increases the incidence of arrhythmias and myocardial injury. PPARγ may be involved in the physical and psychological changes induced by high-intensity exercises.

[Effect of neurotrophin p75 receptor activation on transmural dispersion repolarization in rabbits with myocardial infarction].

OBJECTIVE: To elucidate the effect of neurotrophin p75 receptor (p75NTR)on transmural dispersion repolarization (TDR) of the layers of left ventricular myocytes in rabbits with myocardial infarction (MI). METHODS: Forty Japanese rabbits were divided into four groups (n = 10): (1) Sham group, (2) Heald myocardial infarction (HMI) group, (3) p75 NTR activation group, (4) p75 NTR inhibition group. Cardiomyocytes were isolated with enzyme digestion and the currents were recorded by whole-cell patch-clamp technique. RESULTS: Compared with those in the sham group, the duration of 90% action potential repolarization (APD90) and transmural dispersion repolarization of three layers of left ventricular myocytes were obviously raised (P < 0.05). But significant reduction was observed in p75NTR(-) group. Current densities of Ito and I(Ks, tail) in the p75NTR(+) group and HMI group were significantly reduced (P < 0.05), especially in mid myocytes. And no obvious changes were observed in p75NTR(-) group. CONCLUSION: Activation of p75NTR(+) increases transmural dispersion repolarization, which may lead to the incidence of arrhythmia.

Allocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells.

AIM: Allocryptopine (ALL) is an alkaloid extracted from Corydalis decumbens (Thunb) Pers. Papaveraceae, whereas benzyltetrahydropalmatine (BTHP) is a derivative of tetrahydropalmatine extracted from Corydalis ambigua (Pall) Cham et Schlecht. The aim of this study was to investigate the effects of ALL and BTHP on the human ether-a-go-go related gene (hERG) current expressed in HEK293 cells. METHODS: Cultured HEK293 cells were transiently transfected with hERG channel cDNA plasmid pcDNA3.1 using Lipofectamine. The whole-cell current IHERG was evoked and recorded using Axon MultiClamp 700B amplifier. The drugs were applied via supserfusion. RESULTS: Both ALL and BTHP reversibly suppressed the amplitude and density of IHERG in concentration- and voltage-dependent manners (the respective IC50 value was 49.65 and 22.38 µmol/L). BTHP (30 µmol/L) caused a significant negative shift of the steady-state inactivation curve of IHERG, while ALL (30 µmol/L) did not affect the steady-state inactivation of IHERG. Furthermore, BTHP, but not ALL, shortened the time constants of fast inactivation and slow time constants of deactivation of IHERG. But both the drugs markedly lengthened the time constants for recovery of IHERG from inactivation. Using action potential waveform pulses, it was found that both the drugs at 30 µmol/L significantly suppressed the current densities in the late phase of action potential, but did not significantly affect the current densities in the early phase of action potential. CONCLUSION: Both ALL and BTHP derived from Chinese herbs potently block hERG current.

Frequency- and state-dependent blockade of human ether-a-go-go-related gene K+ channel by arecoline hydrobromide.

BACKGROUND: The rapidly activating delayed rectifier potassium current (I(Kr)), whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene (hERG), is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K(+) current (I(hERG)). METHODS: Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the I(hERG) before and after the exposure to arecoline. RESULTS: Arecoline decreased the amplitude and the density of the I(hERG) in a concentration-dependent manner (IC(50) = 9.55 mmol/L). At test potential of +60 mV, the magnitude of I(hERG) tail at test pulse of -40 mV was reduced from (151.7 ± 6.2) pA/pF to (84.4 ± 7.6) pA/pF (P < 0.01, n = 20) and the magnitude of I(hERG) tail at test pulse of -110 mV was reduced from (-187.5 ± 9.8) pA/pF to (-97.6 ± 12.6) pA/pF (P < 0.01, n = 20). The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of I(hERG) was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of I(hERG) by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. CONCLUSION: Arecoline could potently block I(hERG) in both frequency and state-dependent manner.

[Effect of carvedilol on T-type calcium current in myocytes of non-infarcted area of the rabbit healed myocardial infarction].

This article reports the investigation of the effect of carvedilol (Car) on T-type calcium current (I(Ca,T)) of noninfarcted ventricular myocytes in rabbit models of healed myocardial infarction (HMI). Rabbits with left anterior descending artery ligation were prepared and allowed to recover for 8 weeks, as HMI group. Animals undergoing an identical surgical procedure without coronary ligation were served as the sham-operated group (sham group). Whole cell voltage-clamp techniques were used to measure and compare currents in cells from the different groups. Noting that I(Ca,T) density in HMI cells increased markedly to -2.36 +/- 0.12 pA/pF (at -30 mV) compared with cells of sham, where little I(Ca,T) (-0.35 +/- 0.02 pA/pF) was observed. Meanwhile, further analysis revealed a significant hyperpolarizing shift of steady-state activation curve of I(Ca,T) in HMI cells, where the time constants of deactivation were prolonged and the time of recovery from inactivation was shortened. Finally, the amplitude of I(Ca,T) was increased. Carvedilol (1 micromol x L(-1)) was found to decrease the amplitude of I(Ca,T) to -1.38 +/- 0.07 pA/pF through inhibiting process of I(Ca,T) activation. Furthermore, carvedilol delayed recovery from inactivation of I(Ca,T) and shortened the time constants of deactivation in HMI cells. This study suggested that the application of carvedilol in HMI cells contributes to the dynamic changes in I(Ca,T) and may account for reduction of incidence of arrhythmia after myocardial infarction.