OBJECTIVETo investigate the effect of early intervention by pravastatin with two different dosage on inflammatory factors and endothelial vasodilator function in patients with unstable angina (UA).

METHODS108 patients with UA were investigated consecutively and divided randomly into three groups (group 20 mg, n = 37; group 10 mg, n = 37; group control, n = 34). Blood samples were examined at admission and 4, 8 weeks after the therapy of pravastatin. Fourty patients of UA were chosen from those three groups (15, 15 and 10 cases respectively). The endothelium-dependent vasodilation and the function of vascular endothelium of them were measured. In the dosage of 20 mg pravastatin group non-endothelium-dependent vasodilation in brachial artery was also tested by ultrasound before and 8 weeks after the therapy. Cardiac events were followed up for 2 months.

RESULTS(1) The use of pravastatin in early admission period of UA could significantly reduce inflammatory factors and improve vascular endothelium function, which was more obviously in the group of 20 mg/d than in group of 10 mg/d. These benefits occurred in 4th week and more obviously in 8th week after the therapy. (2) The lipid lowering therapy in the early stage of admission (24 - 48 h) resulted in the reduction of cardiac events in the hospital.

CONCLUSIONThe use of pravastatin 20 mg/d seems better than that of 10 mg/d in all the fields as above in early admission period of UA patients.

Adult ; Aged ; Angina, Unstable ; drug therapy ; Anticholesteremic Agents ; administration & dosage ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Inpatients ; Male ; Middle Aged ; Pravastatin ; administration & dosage ; therapeutic use ; Prospective Studies

PURPOSE: To evaluate the effect of statin treatment on strut coverage after drug-eluting stent (DES) implantation. MATERIALS AND METHODS: In this study, 60 patients were randomly assigned to undergo sirolimus-eluting stent (SES) or biolimus-eluting stent (BES) implantation, after which patients were randomly treated with pitavastatin 2 mg or pravastatin 20 mg for 6 months. The degree of strut coverage was assessed by 6-month follow-up optical coherence tomography, which was performed in 52 DES-implanted patients. RESULTS: The percentages of uncovered struts were 19.4+/-14.7% in pitavastatin-treated patients (n=25) and 19.1+/-15.2% in pravastatin-treated patients (n=27; p=0.927). A lower percentage of uncovered struts was significantly correlated with a lower follow-up low-density lipoprotein (LDL) cholesterol level (r=0.486; p=0.009) and a greater decline of the LDL cholesterol level (r=-0.456; p=0.015) in SES-implanted patients, but not in BES-implanted patients. In SES-implanted patients, the percentage of uncovered struts was significantly lower among those with LDL cholesterol levels of less than 70 mg/dL after 6 months of follow-up (p=0.025), but no significant difference in this variable according to the follow-up LDL cholesterol level was noted among BES-implanted patients (p=0.971). CONCLUSION: Lower follow-up LDL cholesterol levels, especially those less than 70 mg/dL, might have a protective effect against delayed strut coverage after DES implantation. This vascular healing effect of lower LDL cholesterol levels could differ according to the DES type.
Adult ; Coronary Angiography ; *Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Lipoproteins, LDL/blood ; Male ; Middle Aged ; Pravastatin/therapeutic use ; *Prosthesis Implantation ; Quinolines/therapeutic use ; Tomography, Optical Coherence ; Treatment Outcome

OBJECTIVETo investigate the efficacy and safety of adding pravastatin (Pra) on top of standard therapy in non-ischemic heart failure patients.

METHODSA total of 61 patients hospitalized in our hospital from Jan 2005 to Jul 2006 were randomly divided into pravastatin group (Pra 20 mg/d on top of standard therapy, n = 30) and control group (standard therapy, n = 31) and followed 6 months. The changes on cardiac function, flow-mediated vasodilatation (FMD) of brachial artery, plasma TNF-alpha level, liver and kidney function were observed.

RESULTSIn Pra treated patients, FMD of brachial artery significantly increased after 3 months treatments and NYHA stage significantly improved, plasma BNP, TNF-alpha levels and left ventricular end-diastolic dimension significantly decreased, LVEF significantly increased significantly 6 months post therapy compared to baseline (all P < 0.01). In control group, the patients' NYHA stage also significantly improved (P < 0.05) and LVEF tended to be higher (P = 0.052) while FMD, plasma BNP and TNF-alpha levels remained unchanged at 6 months post therapy compared to baseline. In Pra group, the level of TC (P < 0.05) and LDL-C (P = 0.051) also significantly decreased while HDL-C remained unchanged 6 months post therapy. One patient in Pra group discontinued the study drug because of anaphylaxis. No event on liver and kidney dysfunction was noticed.

CONCLUSIONPravastatin was effective and safe in treating non-ischemic heart failure patients and can significantly improve left ventricular remodeling, endothelial and cardiac functions as well as reduce the levels of inflammatory factors.

Adult ; Female ; Heart Failure ; drug therapy ; etiology ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Pravastatin ; therapeutic use ; Ventricular Function, Left

OBJECTIVETo evaluate the interaction of atorvastatin or pravastatin with clopidogrel on platelet activation and aggregation function in patients with acute coronary syndromes (ACS) undergoing coronary stenting.

METHODSBetween April and December 2006, a total of 150 hospitalized ACS patients undergoing coronary stenting were randomized to receive atorvastatin (n = 50), pravastatin (n = 50) or no statin (n = 50) one day post procedure. All patients received standard antiplatelet treatment including aspirin 300 mg/d and loading dose 300 mg of clopidogrel followed by maintenance dose 75 mg/d. The expressions of CD62P and PAC-1 and the maximal platelet aggregation rate (MPAR) induced by 20 micromol/L ADP were measured at day 1 before statin therapy (baseline) and day 3 after procedure.

RESULTSBaseline clinical characteristics and levels of CD62P, PAC-1 and MPAR at the baseline were comparable among three groups. After 3-day statin treatment, the changes of CD62P [(4.69 +/- 16.78)% vs. (1.35 +/- 10.86)% vs. (2.97 +/- 10.21)%], PAC-1 [(12.78 +/- 22.07)% vs. (8.01 +/- 21.23)% vs. (10.65 +/- 21.39)%] and MPAR [(5.44 +/- 18.68)% vs. (7.15 +/- 19.59)% vs. (3.76 +/- 23.42)%] among three groups were not significantly different (all P > 0.05). Subgroup analysis showed that DeltaCD62P [(7.50 +/- 19.35)% vs. (3.24 +/- 11.18)% vs. (2.53 +/- 8.87)%], DeltaPAC-1 [(13.40 +/- 24.62)% vs. (11.28 +/- 19.90)% vs. (10.11 +/- 21.29)%] and DeltaMPAR [(7.56 +/- 19.11)% vs. (7.87 +/- 23.60)% vs. (6.75 +/- 23.30)%] in ACS patients were also similar among three groups (all P > 0.05).

CONCLUSIONNeither atorvastatin nor pravastatin attenuates the antiplatelet function of clopidogrel in ACS patients early post coronary stenting.

Acute Coronary Syndrome ; drug therapy ; therapy ; Aged ; Angioplasty, Balloon, Coronary ; Atorvastatin Calcium ; Drug Interactions ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Pravastatin ; therapeutic use ; Prospective Studies ; Pyrroles ; therapeutic use ; Ticlopidine ; analogs & derivatives ; therapeutic use

OBJECTIVETo explore the anti-atherosclerosis effect of Taizhi'an Capsule (TZA) for providing a theoretical base of its application in preventing coronary heart disease (CHD), by way of observing the effects of TZA and pravastatin (PVT) on vascular endothelial function in senile patients with CHD.

METHODSSeventy-eight Senile patients with CHD were randomly divided into the TZA group and the PVT group, 39 in each group. Changes of carotid arterial intima-media thickness (IMT) and brachial arterial endothelium dependent diastolic function (FMD) before and after treatment were observed by non-invasive ultrasound test technique, and levels of serum nitric oxide (NO) and plasma endothelin-1 (ET-1) were determined as well.

RESULTSAfter TAZ treatment, IMT decreased from 1.21 +/- 0.17 mm to 0.91 +/- 0.13 mm, FMD increased from 5.02 +/- 0.58% to 8.97 +/- 0.39%, ET-1 lowered from 95.93 +/- 19.41 ng/L to 49.35 +/- 53.27 ng/L, and NO enhanced from 42.56 +/- 14.12 mumol/L to 69.84 +/- 21.96 mumol/L; after PVT treatment, the corresponding changes were 1.25 +/- 0.21 mm to 0.88 +/- 0.32 mm, 4.90 +/- 0.37% to 8.12 +/- 0.25%, 89.35 +/- 10.02 ng/L to 47.96 +/- 11.05 ng/L and 51.71 +/- 9.39 mumol/L to 72.93 +/- 16.51 mumol/L, all the changes were statistically significant.

CONCLUSIONTZA can obviously improve the vascular endothelial function in old patients with CHD, which has the anti-atherosclerosis effect similar to that of PVT.

Aged ; Angina Pectoris ; diagnostic imaging ; drug therapy ; physiopathology ; Carotid Arteries ; diagnostic imaging ; pathology ; physiopathology ; Coronary Disease ; diagnostic imaging ; drug therapy ; physiopathology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Endothelium, Vascular ; physiopathology ; Female ; Humans ; Male ; Phytotherapy ; Pravastatin ; therapeutic use ; Ultrasonography

OBJECTIVETo investigate the effects of pravastatin, fosinopril and their combination on ventricular remodeling, cardiac function, tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and matrix metalloproteinases (MMPs) activities after myocardial infarction (MI) in rats.

METHODSAcute myocardial infarction (AMI) was established by ligation of the anterior descending coronary artery in male Sprague-Dawly (SD) rats. Twenty-four hours after the procedure, the 48 surviving rats were grouped randomly as AMI control, fosinopril (10 mg.kg(-1).d(-1)), pravastatin (20 mg.kg(-1).d(-1)) and a combined use of the 2 drugs. Sham-operated group (n = 8) was taken randomly as non-infarction control. Six weeks after treatment with the drugs by gastric gavage, heart function and left ventricular remodeling were assessed. Left ventricular weight (LVW)/body weight (BW) ratio was determined. The relative expression of myocardium TNF-alpha mRNA was assessed by reverse transcription-polymerase chain reaction. Left ventricular myocardium MMPs activities were assessed by Zymography.

RESULTSThere were no significant differences among the four AMI groups in infarction size (P > 0.05). In comparison with the AMI group, left ventricular end-diastolic pressure, left ventricular end-diastolic diameter, LVW/BW all decreased significantly (P < 0.05 - 0.01); while dp/dtmax, dp/dtmin, fractional shortening (FS) and ejection fraction (EF) increased significantly in all three drug-treated groups (P < 0.05 - 0.01); increments of FS, LVEF and dp/dtmax were more evident in the combination group than either the fosinopril or pravastatin group (P < 0.05). The levels of TNF-alpha mRNA in AMI rats treated with fosinopril, pravastatin and their combination reduced 29%, 26% and 33%, respectively (P < 0.01); MMP-2 activity reduced 25%, 30% and 35%, respectively (P < 0.01); MMP-9 activity reduced 20%, 18% and 24%, respectively (P < 0.01). There were no significant differences in other variables among the 3 treatment groups (P > 0.05).

CONCLUSIONPravastatin, fosinopril and their combination showed favorable effects on left ventricular remodeling after AMI in rats and demonstrated improved cardiac function. The combined treatment group yielded better results in the context of improving left ventricular systolic function. These effects could be relevant to the attenuation of increased MMP-2 and MMP-9 activities and left ventricular expression of TNF-alpha.

Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Animals ; Drug Therapy, Combination ; Fosinopril ; administration & dosage ; therapeutic use ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Myocardial Infarction ; drug therapy ; pathology ; physiopathology ; Pravastatin ; administration & dosage ; therapeutic use ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; Ventricular Remodeling ; drug effects

OBJECTIVEStatins inhibit hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity and lower total serum cholesterol levels. We investigated the effects of Pravastatin on neuroprotection and neurogenesis in the dentate gyrus (DG), subventricular zone (SVZ) and striatum after cerebral ischemia in rats.

METHODSThe filament method was used for temporary middle cerebral artery occlusion (tMCAO). Pravastatin or saline post-ischemically were administered at subsequent time points: 6 h after tMCAO, and then on every subsequent day up to day 14 after tMCAO. Neurological outcome was investigated by using a neuroscore, the beam balance test and the rotarod test. Cholesterol and triglycerides levels were determined by blood sample analysis prior to sacrifice. Infarct area was calculated by microtubule-associated protein 2 (MAP2) staining. Neurogenesis was evaluated by triple staining with bromodeoxyuridine (BrdU), doublecortin (DCX), and neuronal nuclei (NeuN).

RESULTSCompared with the control groups, Pravastatin treated animals were significantly improved in neurological outcome in rotarod test, with smaller infarct size. Pravastatin increased BrdU-positive cells number in the DG (P = 0.0029) and the SVZ (P = 0.0280) but not in the striatum (P = 0.3929). Furthermore, Pravastatin increased BrdU-labeled DCX positive cells number in the DG (P = 0.0031), SVZ (P = 0.0316) and striatum (P = 0.0073). We also observed a DCX-positive cells stream from the SVZ to the striatum, suggesting a migration route of those immature neurons. No significant differences of total serum cholesterol and triglycerides were observed between groups.

CONCLUSIONThe Pravastatin administration strategy is safe and could promote neurological recovery in ischemic stroke. Pravastatin induces neurogenesis in the DG and SVZ, and increases the number of migration cells in the striatum. These effects are independent of the cholesterol-lowering property of Pravastatin.

Animals ; Brain Ischemia ; drug therapy ; pathology ; physiopathology ; Bromodeoxyuridine ; metabolism ; Cell Count ; methods ; Cell Proliferation ; drug effects ; Disease Models, Animal ; Male ; Microtubule-Associated Proteins ; metabolism ; Neurologic Examination ; methods ; Neurons ; drug effects ; physiology ; Neuropeptides ; metabolism ; Neuroprotective Agents ; therapeutic use ; Phosphopyruvate Hydratase ; metabolism ; Pravastatin ; therapeutic use ; Rats ; Rats, Wistar ; Time Factors

BACKGROUND: Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several studies show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nω-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra. METHODS: Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day. Giving Pra (L-NAME + Pra, Control + Pra, n = 8) or normal saline (NS; L-NAME + NS, Control + NS, n = 8) from gestational 8th to 18th day, the mice were sacrificed on day 18 and their liver and placental tissues were collected. Then the activation of mTOR and its substrates in the liver and placenta were detected. And the association between mTOR activation and serum free fatty acid (FFA) levels and the expression of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) were evaluated using Pearson correlation test. Differences between groups were analyzed using independent t-test or one-way analysis of variance (ANOVA). RESULTS: Both in the maternal liver and placenta, the activation of mTOR protein and its effect on substrates increased significantly in the L-NAME + NS group and decreased significantly in the L-NAME + Pra group. The p-mTOR/mTOR protein ratio decreased in the L-NAME + Pra group significantly than that in the L-NAME + NS group both in liver and placenta (liver: 0.74 ± 0.08 vs. 0.85 ± 0.06, t = 2.95, P < 0.05; placenta: 0.63 ± 0.06 vs. 0.77 ± 0.06, t = 4.64, P < 0.05). The activation of mTOR protein in the liver and placenta negatively correlated with the expression of LCHAD in the L-NAME + NS group (liver: r = -0.745, P < 0.05; placenta: r = -0.833, P < 0.05) and that in the maternal liver negatively correlated with the expression of LCHAD (r = -0.733, P < 0.05) and positively with the serum FFA levels (r = 0.841, P < 0.05) in the L-NAME + Pra group. CONCLUSION The inhibition of mTOR signaling pathway might be involved in the regulation of FAO in mouse model treated with Pra.
Animals ; Blotting, Western ; Fatty Acids ; metabolism ; Female ; Immunohistochemistry ; Liver ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; Oxidation-Reduction ; drug effects ; Placenta ; drug effects ; metabolism ; Pravastatin ; therapeutic use ; Pre-Eclampsia ; drug therapy ; Pregnancy ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; metabolism