Objective To evaluate the efficacy and safety of trimetazidine (TMZ) for chronic congestive heart failure. Methods We searched The Cochrane Library (Issue 3, 2006), MEDLINE (1990-2006), EMBASE (1990-2004), and the Chinese Biomedicine Database (1990- 2006 ) for parallel group randomized controlled trials (RCTs) and cross-over design trials comparing TMZ and placebo or open controls for patients with heart failure.We used The Cochrane Collaboration’s RevMan 4.2 software for data analyses. Results Four RCTs and two cross-over design trials were included. Meta-analyses showed that: compared with the control group, TMZ may improve the NYHA cardiac functional grade (RR 0.85, 95%CI 0.76 to 0.95), increase the total exercise time (WMD 51.40 seconds, 95%CI 15.56 to 87.25), the maximal metabolic equivalents (WMD 0.82, 95%CI 0.28 to 1.37), and the ejection fraction (WMD 7.29%, 95%CI 6.28 to 8.31), but may decrease the left ventricular end-diastolic volume (WMD –12.19 ml, 95%CI –15.29 to –9.09), the left ventricular end-diastolic diameter (WMD –6.05 mm, 95%CI –7.10 to –4.99), the left ventricular end-systolic volume (WMD –16.94 ml, 95%CI –20.34 to –13.55), the left ventricular end-systolic diameter (WMD –5.42 mm, 95%CI –5.98 to –4.86), and the serum brain natriuretic peptide (WMD –239.59 pg/ml, 95%CI –276.53 to –202.65). TMZ may also improve the quality of life (WMD 12.36, 95%CI 5.16 to 19.55). Conclusions TMZ plus standard medical therapy has a beneficial effect on the indices of cardiac function, and may also improve the patient’s quality of life. However, because available RCTs for this systematic review are too small and poor quality, (mainly focusing on the heart failure induced by ischemic heart diseases and merely taking intermediate indices as outcome measures), further high-quality large-scale RCTs with death as the endpoint and which include subgroup analysis of non-ischemic heart failure, are required in order to provide more reliable evidence.
Objective To evaluate the efficacy and safety of trimetazidine (TMZ) in the treatment of Stable Angina Pectoris (SAP). Methods Randomized controlled trials (RCTs) on the efficacy and safety of Trimetazidine in treating patients with SAP were retrieved in the following databases as CNKI (1997 to June 2011), WanFang Data (1989 to June 2011), MEDLINE (1966 to June 2011), EMbase (1974 to June 2011), CBM (1989 to June 2011) and Cochrane Central Database (1989 to June 2011). The literature which met the inclusion and exclusion criteria were selected, data were extracted, the quality was evaluated, and meta-analysis was performed by using RevMan 5.0 software. Results A total of 15 RCTs involving 1 500 patients were included. The meta-analysis showed that, compared with the control group, TMZ was significantly superior in the following 5 aspects: the time to 1 mm drop of ST segment (WMD=0.84, 95%CI 0.74 to 0.93, P=0.000 01), duration of doing exercise (WMD=0.82, 95%CI 0.73 to 0.91, P=0.000 01), and time to onset of angina (WMD=1.18, 95%CI 0.87 to 1.50, Plt;0.000 01) in the treadmill test, weekly mean number of angina attacks (WMD= –1.79, 95%CI –1.93 to –1.66, Plt;0.000 01), and weekly side effects between TMZ and the control group (RR=0.83, 95%CI 0.52 to 1.32, P=0.42). Conclusion Based on current studies, TMZ is superior to other medicines in the control group for SAP at present, and it has no significant difference in side effects compared with the control group, so it is regarded as an effective and safe drug. For the quality restrictions and possible publication bias of the included studies, this conclusion needs to be confirmed by more high quality, large sample, multi-center, double blind RCTs.
ObjectiveTo explore the protective effect of low-molecular-weight heparin calcium (LHC) combined with trimetazidine on intestinal smooth muscle of intestinal acute mesangial vein thrombosis (AMVT) in rats and it's mechanism of effect. MethodsA total of 120 SD male rats were randomly divided into three groups, with 40 rats in each group. LHC group: after the AMVT model established, rats were subcutaneous injection the LHC (30 U/100 g) per 12 h until 72 h after surgery. LHC+trimetazidine group (LHCT group): after the AMVT model established, rats were subcutaneous injection the LHC (30 U/100 g) and tail vein injection the trimetazidine (10 mg/kg) per 12 h until 72 h after surgery. Normal saline group (NS group): after the AMVT model established, rats were subcutaneous injection the NS (0.2 mL/100 g) per 12 h until 72 after surgery. The AMVT model were established by blocking superior mesenteric vein of 8 cm and the edge vein arch. Vena cava blood samples and intestinal segments were collected sequentially at 6 h, 12 h, 24 h, 48 h and 72 h afrer surgery. The levels of malondialdehyde (MDA) and creatine kinase (CK) in the blood, and the level of ATP in the intestinal tissue samples were measured with ELISA. Intestinal tissue were taken from the rats for inestinal tissue section, stained with hematoxylin and eosin, examined under light microscopy and evaluated histopathologically using mesemeche scoring system at different time. ResultsCompared with the LHC group and NS group, the levels of MDA and CK in blood and histopathology score of intestinal tissues in rats were significantly decreased, and the level of ATP significantly increased in LHCT group at different time point (P < 0.05). ConclusionTrimetazidine can improve intestinal smooth muscle energy metabolism in the AMVT disease, comined with LHC early can avoid intestinal smooth muscle wall permeability coagulation necrosis and reduce the intestinal smooth muscle damage.
Objective To investigate the role and mechanisms of trimetazidine (TMZ) in intensive care unit-acquired weakness (ICU-AW). Methods Seventy wild-type male C57BL/6 mice were selected and the ICU-AW mouse model was constructed by intraperitoneal injection of different concentrations of lipopolysaccharide (LPS). The body weights, grip strengths, and 96-hour survival rates of each group were observed, and the optimal concentration of LPS and time of sampling were screened out, the mRNA and protein expression of the gastrocnemius muscle atrophic proteins Atrogin-1 and muscle-specific RING finger protein 1 (MuRF1) were further detected to verify the success of modelling, and LPS (12 mg/kg) was used as the subsequent modelling concentration according to the preliminary results. After successful modelling, another 70 mice were randomly divided into normal control group (Normal group), LPS solvent (Vehicle) group, LPS group, LPS+TMZ solvent group, LPS+TMZ group, LPS+TMZ+AC-YVAD-CMK (AC) solvent group, and LPS+TMZ+AC group, with 10 mice in each group. The Normal group did not have any intervention; the Vehicle group was injected intraperitoneally with an equal volume of saline with LPS; the remaining groups were injected intraperitoneally with LPS (12 mg/kg); after the completion of the LPS injection, the LPS+TMZ group, the LPS+TMZ+AC solvent group, and the LPS+TMZ+AC group were given TMZ (5 mg/kg) by gastric gavage once a day for 4 days. The LPS+TMZ solvent group was given TMZ equivalent saline gavage once a day for 4 days. The LPS+TMZ+AC group was injected intraperitoneally with the cysteinyl aspartate specific proteinase 1 (Caspase-1) inhibitor AC-YVAD-CMK (AC, 6.5 mg/kg) 1 h before LPS injection, and the LPS+TMZ+AC solvent group was injected with an equal amount of AC solvent phosphate buffer. At the end of TMZ treatment, body weight, grip strength, 96-hour survival rate, mRNA and protein expression of MuRF1, Atrogin-1, Caspase-1, and gasdermin D (GSDMD) in gastrocnemius muscle, as well as serum IL-1β and IL-18 concentrations in mice were detected in each group, and the gastrocnemius muscle was stained with HE to observe histopathological changes. Results Compared with the Normal group, mice in the LPS (12 mg/kg) and LPS (14 mg/kg) groups showed significant decreases in body weight and grasping strength and the weakening was most obvious at 3 - 5 d (P<0.05), but the survival rate of the LPS (12 mg/kg) group was higher than that of the LPS (14 mg/kg) group (P<0.05), the HE staining of gastrocnemius muscle showed that the mice in the LPS (12 mg/kg) group was significantly atrophied compared with that of the Normal group, and the gene and protein expression of MuRF1 and Atrogin-1 were significantly elevated (P<0.05), and the mice injected with LPS (12 mg/kg) for 4 days (96 h) were finally selected as the conditions for subsequent experimental modelling and sampling.The mRNA and protein expression of Caspase-1 and GSDMD in skeletal muscle was significantly higher in the LPS group compared with the Normal and Vehicle groups (P<0.01), and the concentrations of serum IL-1β and IL-18 were significantly higher(P<0.01). Mice in the TMZ group showed significant improvement in body weight, grip strength, survival rate, and degree of muscle atrophy compared with the LPS and TMZ solvent groups (P<0.05); gene and protein levels of MuRF1, Atrogin-1, Caspase-1, and GSDMD in the gastrocnemius muscle were significantly reduced (P<0.05); and levels of serum IL-1β and IL-18 were significantly reduced (P<0.05) ); the mice in the LPS+TMZ+AC group had significantly improved body weight, grip strength, survival rate, and muscle atrophy compared with the LPS+TMZ group and the LPS+TMZ+AC solvent group (P<0.05), and the gene and protein contents of MuRF1, Atrogin-1, Caspase-1, and GSDMD in the gastrocnemius muscle were reduced (P<0.05), and the serum IL-1β and IL -18 concentrations were reduced (P<0.05). Conclusion TMZ is able to exert a skeletal muscle protective effect by inhibiting Caspase-1/GSDMD-mediated pyroptosis, which is an important reference for the prevention and treatment of ICU-AW.