Metabolic study of trimetazidine using ultra-high performance liquid chromatography-tandem mass spectrometry

Abstract In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known-as well as hitherto unknown-trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0-4 h, 4-8 h, 8-12 h, and 12-24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites

Effects of different doses of simvastatin and atorvastatin combined with trimetazidine on blood lipids and cardiac function in patients with chronic heart failure / 中国基层医药

Objective:To investigate the effects of different doses of simvastatin and atorvastatin combined with trimetazidine on blood lipids and cardiac function in patients with chronic heart failure.Methods:A total of 100 patients with chronic heart failure who received treatment in Jinan Second People's Hospital from September 2019 to August 2021 were included in this study. These patients were divided into three groups according to different treatment methods: group A ( n = 33), group B ( n = 33), and group C ( n = 34). Group A was treated with a conventional dose of simvastatin combined with trimetazidine. Group B was treated with a high dose of simvastatin combined with trimetazidine. Group C was treated with atorvastatin combined with trimetazidine. All patients were treated for 6 months. Cardiac function, blood lipids, inflammatory factors, and excellent and good rates of therapeutic effects post-treatment were compared between the three groups. The adverse events during the treatment were recorded. Results:There were no significant differences in blood lipids, cardiac function, inflammatory factors, and excellent and good rates of therapeutic effects between the two groups (all P > 0.05). After 6 months of treatment, high-density lipoprotein cholesterol [(1.99 ± 0.25) mmol/L, (2.01 ± 0.16) mmol/L] and left ventricular ejection fraction [(51.29 ± 4.15)%, (51.37 ± 4.44)%] in groups B and C were significantly higher than those in group A [(1.52 ± 0.16) mmol/L, (42.28 ± 4.86)%, t = 9.10, 6.24; 8.10, 11.38, all P < 0.05). Caspase-1 [(42.33 ± 3.19) ng/L, (41.87 ± 3.55) ng/L], interleukin-18 [(54.55 ± 4.39) ng/L, (53.98 ± 4.45) ng/L], left ventricular end-systolic diameter [(35.13 ± 2.13) mm, (35.68 ± 2.46) mm], left ventricular end-diastolic diameter [(44.39 ± 3.65) mm, (44.42 ± 3.32) mm], low-density lipoprotein cholesterol [(2.69 ± 0.39) mmol/L, (2.57 ± 0.13) mmol/L], total cholesterol [(3.79 ± 0.13 ) mmol/L, (3.56 ± 0.69) mmol/L], triacylglycerol [(1.12 ± 0.05) mmol/L, (1.10 ± 0.07) mmol/L] levels in groups B and C were significantly lower than those in group A [(68.41 ±10.23) ng/L, (88.37 ± 6.65) ng/L, (42.63 ± 3.13) mm, (51.68 ± 5.42) mm, (3.13 ± 0.11) mmol/L, (4.21 ± 0.11) mmol/L, (1.51 ± 0.11) mmol/L, t = -13.98, -24.38, -14.27, -24.95, -6.41, -5.64, -8.00, -10.12, -14.17, -18.54, -12.53, -19.01, -5.35, -18.26, all P < 0.05]. 6-minute walking distances [(352.19 ± 25.4) m, (351.74 ± 24.29) m] in groups B and C were significantly longer than that in group A [(319.71 ± 21.11) m, t = 6.63, 5.75, both P < 0.05). The excellent and good rates at 3 and 6 months after surgery in group B was significantly higher than that in group A ( χ2 = 4.00, 4.16, both P < 0.05), but the incidence of adverse reactions in group B [18.18% (6/33)] was significantly higher than 3.03% (1/33) in group A and 2.94% (1/34) in group C (both P < 0.05). There was no significant difference in the incidence of adverse reactions between group A and group C ( P > 0.05). Conclusion:Atorvastatin and high-dose simvastatin alone combined with trimetazidine can achieve good therapeutic effects on chronic heart failure. Both combined therapies are beneficial to improve heart function and reduce myocardial damage. However, atorvastatin combined with trimetazidine is safer than high-dose simvastatin combined with trimetazidine.

China Hospital Pharmacovigilance System-based study of trimetazidine-associated Parkinson's syndrome / 中国基层医药

Objective:To evaluate the active monitoring methods and population characteristics of trimetazidine-associated Parkinson's syndrome.Methods:The clinical data of patients with trimetazidine-associated Parkinson's syndrome who received treatment in Liaocheng People's Hospital from January 2019 to December 2020 were retrospectively analyzed using the China Hospital Pharmacovigilance System (CHPS).Results:In 4 883 patients included in the study,167 patients were alarmed by CHPS, of which 26 patients were confirmed positive by manual rechecks. The rate of positive pre-alarming by CHPS was 15.57%. The actual incidence of trimetazidine-associated Parkinson's syndrome was 0.53%. The average age of the 26 patients with Parkinson's syndrome was (75.08 ± 10.79) years. None of the 26 patients had a past history/family history of idiopathic Parkinson's disease. There were 21 patients (80.77%) aged over 65 years, 19 patients (73.08%) with a history of ischemic encephalopathy, 17 patients (65.38%) with positive symptoms in both limbs, 20 patients (76.92%) with abnormal brain CT or MRI findings, and 21 patients (80.77%) with medication doses of 60-70 mg/d. Among the 26 patients, 18 were female patients (69.23%) and 18 were patients with normal renal function (69.23%). The follow-up results showed that trimetazidine administration was not terminated in 14 patients (53.85%), symptoms were not alleviated or worsened in 8 patients (30.77%), and symptoms were alleviated or disappeared in 18 patients (69.23%).Conclusion:The use of CHPS can timely detect trimetazidine-associated Parkinson's syndrome. CHPS has significant advantages over traditional monitoring modes. Age > 65 years and a previous history of ischemic encephalopathy are risk factors for developing trimetazidine-associated Parkinson's syndrome. No history/family history of idiopathic Parkinson's disease, positive Alzheimer's disease symptoms in both limbs and abnormal brain CT and MRI findings contribute to early diagnosis and differentiation of trimetazidine- associated Parkinson's syndrome. Trimetazidine-associated Parkinson's syndrome is more common in women than in men. Trimetazidine-associated Parkinson's syndrome can also occur in a population with normal renal function or under a normal trimetazidine dose condition. Trimetazidine-associated Parkinson's syndrome is relatively rare. Patients with trimetazidine- associated Parkinson's syndrome have low awareness. Because of the difficult diagnosis and serious consequences, there is a need to strengthen research on trimetazidine-associated Parkinson's syndrome.

A new combination of naringin and trimetazidine protect kidney Mitochondria dysfunction induced by renal Ischemia / Reperfusion injury in rat

Abstract Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.

Research progress on the role of transient receptor potential canonical 6 in ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) refers to the reperfusion injury caused by the recovery of blood supply of ischemic tissues or organs, which commonly occurs in organ transplantation and other surgical procedures. IRI may cause a series of severe clinical issues, such as delayed graft function, acute kidney injury, myocardial infarction, ischemic stroke and circulatory arrest, etc. These events yield high incidence and fatality. At present, no effective solution has been available. Transient receptor potential canonical 6 (TRPC6), a member of Ca2+ channel family, is highly expressed in multiple types of cells. It may adjust many physiological functions by regulating intracellular Ca2+ concentration, which has become an important target for developing therapeutic drugs for multiple diseases. In this article, research progresses on the introduction and function of TRPC6, the association between TRPC6 and IRI and the therapeutic prospect of TRPC6 targeted drugs in IRI were reviewed, aiming to provide novel insights into the prevention and treatment of IRI during organ transplantation

Naringin and trimetazidine improve baroreflex sensitivity and nucleus tractus solitarius electrical activity in renal ischemia-reperfusion injury / Naringin and trimetazidine improve baroreflex sensitivity and nucleus tractus solitarius electrical activity in renal ischemia-reperfusion injury

Resumo Fundamento: O núcleo do trato solitário (NTS) é uma área do cérebro que desempenha um papel fundamental na regulação renal e cardiovascular através dos impulsos dos barorreceptores. Objetivos: O objetivo deste estudo foi avaliar o efeito da Naringina (NAR) e trimetazidina (TMZ), isoladamente e combinadas, na atividade elétrica do NTS e na sensibilidade barorreflexa (SBR) na lesão de isquemia e reperfusão (I/R) renal. Métodos: Foram utilizados quarenta ratos machos Sprague-Dawley (200-250 g), alocados em 5 grupos com 8 ratos cada. Grupos: 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; e 5) TMZ5 + NAR100. A veia femoral esquerda foi canulada para infundir a solução salina ou droga e avaliar a SBR. A I/R foi induzida por oclusão dos pedículos renais por 45 min, seguida de reperfusão de 4 horas. O eletroencefalograma local do NTS foi registrado antes, durante a isquemia e durante a reperfusão. A fenilefrina foi injetada por via intravenosa para avaliar a SBR ao final do tempo de reperfusão. Os dados foram analisados por ANOVA de duas vias com medidas repetidas seguida pelo teste post hoc de Tukey. Um valor de p<0,05 foi considerado como significativo. Resultados: As ondas elétricas do NTS não se alteraram durante o tempo de isquemia, mas diminuíram significativamente durante todos os tempos de reperfusão. A atividade elétrica do NTS e a SBR foram reduzidas drasticamente em ratos com lesão I/R; no entanto, a administração de NAR e TMZ, isoladamente e combinadas, melhorou significativamente essas alterações em ratos com lesão I/R. Conclusões: Os resultados mostraram que a lesão de I/R leva à redução da atividade elétrica da SBR e do NTS, e pode haver uma ligação entre a I/R e a diminuição da SBR. Além disso, a NAR e a TMZ são agentes promissores para tratar complicações de I/R.

Abstract Background: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses. Objectives: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury. Methods: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant. Results: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury. Conclusions: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.

Trimetazidine reduces formation of neutrophil extracellular traps via inhibiting autophagy / 中国药理学通报

Aim To study the effects of trimetazidine (TMZ)on theformationof neutrophil extracellular traps (NETs) induced by oxidized low-density lipoprotein (ox-LDL) in vitro and its relationship associated with cell autophagy. Methods The bone marrow neutrophils of mice were extracted by density gradient centrifugation,and NETs induction model was established using ox-LDL. Furthermore, TMZ, autophagy inhibitor LY294002 and autophagy inducer Rapamycin were added to disturb the induction of NETs induced by ox-LDL. The production of NETs marker MPO-DNA and the content of cfDNA/nets in the supernatantwere observed. Meanwhile, Western blot was employed to determine the protein expression of myeloperoxidase (MPO),beclin-l and LC3b in neutrophils. Results Treatment of ox-LDL to adhered neutrophils could lead to the formation of extracellular MPO-DNA and cfDNA/nets generation in a time-and concentration-dependent manner. The protein expression of LC3b,beclin-1 and MPO in neutrophils was up-regulated after treatedwith ox-LDL. TMZ pretreatment significantly inhibited NETs release and reduced the protein expression of LC3b,beclin-1 and MPO in neutrophils,which could be simulated by PI3K/AKT pathway blocker LY294002, while AKT/mTOR inhibitor rapamycin preconditioning did the opposite. Conclusions Ox-LDL-induces the formation of NETs in a time-and concentration-dependent manner. TMZ could down-regulate the level of autophagy and neutrophils, inhibit the induction of ox-LDL on NETs and reduce the release of NETs.

Evaluation and comparison of the hepatoprotective effects of trimetazidine and lovastatin against doxorubicin-induced hepatotoxicity

Background: The dosage of highly efficacious anti-cancer drug doxorubicin (DOX) is often constrained as limited data exists on its hepatotoxic potential. The present study not only evaluated the extent of its hepatotoxicity but also aimed at curtailing it, by administration of two drugs i.e. trimetazidine and lovastatin, both of which are otherwise known for their cardioprotective benefits.Methods: The study was a lab-based randomized controlled study on mice. Acute toxicity was introduced with DOX injected intraperitoneally at a dose of 10 mg/kg and it was protected by oral administration of trimetazidine and lovastatin, both in a dose of 10 mg/kg. The protective drugs were both given for five and ten consecutive days in short and long term study designs whereby DOX was administered on the third and eighth days of the respective studies.Results: Doxorubicin administration caused significant hepatotoxicity reflected by markedly raised biomarkers (serum alanine aminotransferase and aspartate aminotransferase) and mild inflammation of liver parenchyma with a score of 4 as per Ishak grading scale. The changes were significantly attenuated by both the protective drugs in the ten days study design. However, in the five days study, lovastatin exhibited more significant hepatoprotection than trimetazidine.Conclusions: Pretreatment with two commonly available, cost effective and safe drugs can effectively prevent a potentially life-threatening adverse effect of DOX. This approach might prove very convenient for the health care providers as well as for the patients without burdening the economics.

Clinical effect of trimetazidine combined with ticagrelor in the treatment of unstable angina pectoris complicated with chronic heart failure / 中国基层医药

Objective@#To observe the clinical efficacy and safety of trimetazidine combined with ticagrelor in the treatment of unstable angina pectoris (UAP) complicated with chronic heart failure (CHF).@*Methods@#From January 2016 to September 2018, 60 UAP patients complicated with CHF in Taizhou Cancer Hospital were selected and randomly divided into two groups according to the random number table method, with 30 cases in each group.The control group was given ticagrelor, while the observation group was given ticagrelor + trimetazidine.The clinical efficacy, angina attack, cardiac function indicators, adverse reactions were compared between the two groups.@*Results@#The total effective rate of the observation group was 96.67%, which was higher than 80.00% of the control group (χ2=4.043, P<0.05). With in 3 months after treatment, the number of angina attacks (6.59±1.32)times and the duration of single angina pectoris [(2.24±0.92)min] in the observation group were all lower than those in the control group(t=4.277, 4.076, all P<0.05). After treatment, the left ventricular ejection fraction [(49.36±6.25)%] and stroke output [(76.29±5.31)mL] of the observation group were higher than those of the control group (t=4.066, 4.093, all P<0.05), and the level of brain natriuretic peptide [(378.32±27.82)μg/L] of the observation group was lower than that of the control group (t=4.152, P<0.05). The incidence rate of adverse reactions of the observation group was 6.67%, which of the control group was 3.33%, there was no statistically significant difference between the two groups (χ2=0.351, P>0.05).@*Conclusion@#The combination of ticagrelor and trimetazidine can effectively reduce the attack of angina pectoris, improve cardiac function and has less adverse reactions.It is effective and safe for UAP patients complicated with CHF.

Trimetazidine in angina and poor muscle function: protocol for a randomized controlled study / 中华医学杂志(英文版)

Background@#Low handgrip strength (HS) and declining gait speed (GS) are increasingly obvious with aging, requiring effective, and safe medication for treatment. Trimetazidine (TMZ) modified release tablets, a common anti-angina drug, has potential benefits for alleviating the condition, but this has not yet been fully studied and therefore is the aim of this study.@*Methods@#This is a prospective randomized controlled study. Fifty-eight eligible patients will be randomly assigned to one of two study groups: TMZ group or control group. For the TMZ group, a dose of 35 mg of oral TMZ will be administered with a meal twice a day for 3 months, in addition to any conventional treatments for angina. Only conventional treatments for angina will be administrated in the control group. The primary outcome will be the 6-min walking distance and the secondary outcomes will be: muscle strength (HS and pinch strength), GS, muscle endurance (five times sit-to-stand test), balance maintenance (tandem standing test), and the frequency of angina per week. Additionally, body mass index, circumferences (biceps, waist, hip, and calf), albumin levels, and the score on a five-question scale for sarcopenia will be obtained during the study.@*Discussion@#This study aims to evaluate the usefulness of TMZ in a population with poor muscle function. The results may provide an effective and safe medical treatment to people with low muscle strength or physical performance.@*Trial registration@#Chinese Clinical Trial Registry, ChiCTR1800015000; www.chictr.org.cn/showproj.aspx?proj=25445.

Therapeutic effect of trimetazidine on coronary heart disease combined chronic heart failure and its in‐fluence on cardiac function ,levels of plasma BNP and serum hsCRP / 心血管康复医学杂志

Objective :To study therapeutic effect of trimetazidine on coronary heart disease combined chronic heart failure (CHD‐CHF) and its influence on cardiac function ,levels of plasma BNP and serum hsCRP .Methods :A total of 92 CHD‐CHF patients treated in our hospital from Jan 2016 to Jun 2017 were randomly and equally divided into routine treatment group and trimetazidine group (received trimetazidine based on routine treatment ).Both groups were treated for three months.Heart rate (HR) ,blood pressure (BP) ,cardiac function indexes ,levels of plasma BNP and serum hsCRP before and after treatment ,and total effective rate were compared between two groups .Results :Total effective rate of trimetazi‐dine group was significantly higher than that of routine treatment group (95.65% vs.76.09%) , P＝0.007. Compared with routine treatment group after treatment ,there were significant reductions in HR [ (83.58 ± 5.17) beats／min vs. (72.69 ± 5.06) beats／min] ,BP [ (131.74 ± 12.98)／(83.25 ± 4.35) mmHg vs.(120.46 ± 12.53)／(79.25 ± 4.07) mmHg] ,LVESd [(41.21 ± 2.26) mm vs.(36.78 ± 2.07) mm] ,LVEDd [(57.91 ± 2.04) mm vs.(51.03 ± 1.89) mm] , levels of plasma BNP [ (262.94 ± 11.35) pg／ml vs.(223.42 ± 11.17) pg／ml] ,and serum hsCRP [ (5.86 ± 1.54) mg／L vs.(2.37 ± 0.95) mg／L] ,and significant rise in LVEF [ (53.72 ± 4.83)% vs.(61.37 ± 5.19)%] and 6MWD [ (285.42 ± 21.74) m vs.(376.08 ± 21.95) m] in trimetazidine group ,P＜0.01 all.Conclusion :Trimetazidine possesses significant therapeutic effect on CHD‐CHF.It can significantly improve cardiac function and reduce HR ,BP ,levels of plasma BNP and serum hsCRP ,which is worth extending .

Value of early diagnosis and prognosis assessment of serum sCD 40L and NT‐proBNP levels detection in aged patients with heart failure / 心血管康复医学杂志

Objective :To study application value of serum sCD40L and NT‐proBNP levels detection in early diagnosis and prognosis assessment of aged patients with heart failure (HF).Methods :A total of 73 aged HF patients treated in our hospital from Feb 2015 to Feb 2017 were selected as HF group .According to NYHA cardiac function class , HF group was divided into class Ⅱ group (n＝37) and class Ⅲ group (n＝36).A total of 112 healthy people ,who had a physical examination in our hospital at the corresponding period ,were selected as health group .HF group were treated for one month .Incidence of major adverse cardiovascular events (MACE) within one‐month was re‐corded .According to MACE during one‐month follow‐up ,HF group was divided into MACE group (n＝20) and no MACE group (n＝53).Serum levels of sCD40L and NT‐proBNP were measured and compared between HF group before treatment and health group ;class Ⅱ group and class Ⅲ group before and after treatment ;MACE group and no MACE group .Results :There were significant rise in serum levels of sCD 40L and NT‐proBNP in HF group be‐fore treatment compared with health group , P＝0. 001 all.Compared with before treatment ,there were significant reductions in serum levels of sCD40L and NT‐proBNP in class Ⅱ group and class Ⅲ group , P＝ 0.001 all.After treatment ,compared with class Ⅲ group there was significant reduction in serum level of sCD40L [ (8.31 ± 0.76) ng／ml vs .(7.37 ± 0.81) ng／ml] in class Ⅱ group , P＝0. 001. During one‐month follow‐up ,20 cases of MACE oc‐curred in HF group (n＝73) and incidence of MACE in HF group was 27.40% .Compared with MACE group ,there were significant reductions in serum levels of sCD 40L [ (10.26 ± 1.54) ng／ml vs.(11. 49 ± 1. 81) ng／ml] and NT‐proBNP [(612. 28 ± 122. 76) ng／L vs.(1072.25 ± 245.68) ng／L] in no MACE group ,P＝0. 001 all.Conclusion :Se‐rum sCD40L and NT‐proBNP levels detection possesses good application value in early diagnosis and prognosis assess‐ment for aged patients with HF ,which is worth extending .

Therapeutic effect of trimetazidine hydrochloride on aged patients with acute cardiomyopathy in acute phase and its influence on serum cytokine levels and cardiac function / 心血管康复医学杂志

Objective :To explore therapeutic effect of trimetazidine hydrochloride on aged patients with acute ische-mic cardiomyopathy in acute phase and its influence on serum cytokine levels and cardiac function .Methods : A total of 90 aged patients with acute cardiomyopathy ,who were treated in our hospital from Dec 2014 to Dec 2016 ,were selected .Patients were randomly and equally divided into routine treatment group and trimetazidine group (received trimetazidine based on routine treatment ) ,both groups were treated for 12 weeks .Left ventricular ejection fraction (LVEF) ,left ventricular end-systolic dimension (LVESd) ,left ventricular end-diastolic dimension (LVEDd) ,ser-um levels of tumor necrosis factor (TNF)-α and interleukin (IL )-6 before and after treatment ,and therapeutic effect were measured and compared between two groups .Results : Total effective rate of trimetazidine group was significantly higher than that of routine treatment group (97-78% vs .77-77%) , P＝0-004- Compared with before treatment ,there were significant reductions in serum levels of TNF-α and IL-6 in two groups ;significant rise in LVEF ,and significant reductions in LVEDd and LVESd in trimetazidine group after treatment , P＜ 0-05 or ＜0-01- Compared with routine treatment group after treatment , there was significant rise in LVEF [ (60-89 ± 5-22)% vs.(65-01 ± 6-01 )%] , and significant reductions in LVESd [ (34-02 ± 5-00 ) mm vs .(30-27 ± 4-80 ) mm] ,LVEDd [ (51-22 ± 7-02) mm vs.(46-21 ± 5-44) mm] ,serum levels of TNF-α [ (282-97 ± 59-44) pg／ml vs. (248-89 ± 45-33) pg／ml] and IL-6 [ (721-02 ± 165-00 ) pg／ml vs.(630-89 ± 102-80 ) pg／ml] in trimetazidine group ,P＜0-01 all.Conclusion : Trimetazidine hydrochloride possesses certain anti-inflammation effect ,can signifi-cantly improve cardiac function and therapeutic effect in aged patients with acute cardiomyopathy ,which is worth extending .

Meta analysis of atorvastatin combined with trimetazidine in the treatment of angina pectoris of coronary heart disease / 中国医师杂志

Objective To evaluate efficacy and safety of Atorvastatin combined with trimetazidine Sibutramine treating angina pectoris of coronary heart disease.Methods Of computer retrieval China National Knowledge Infrastructure (CNKI),Wanfang database,VIP database and search atorvastatin statins combined with trimetazidine trimetazidine in the treatment of angina pectoris of coronary heart disease:a randomized controlled trial,according to Jadad scale to evaluate the quality of the included studies and extracted data.Meta analysis was performed using RevMan 5.3.Results In accordance with the inclusion criteria were included in the 18 study,a total of 1 848 patients.The software of RevMan 5.3 on cardiovascular events incidence,clinical curative effect,angina pectoris,blood lipid [total cholesterol (TC),triglyceride (TG),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C)],the improvement of cardiac function [including cardiac index left ventricular end diastolic diameter (LVEDD),left ventricular end systolic diameter (LVESD)] and the adverse reactions of meta analysis showed that compared with pure atorvastatin,atorvastatin combined with trimetazidine can reduce the incidence of cardiovascular events [OR =0.19,95％ Cl (0.11,0.35),P＜0.01],reduce seizure frequency and duration of angina [WMD =-1.52,95％ CI (-1.84,-0.99),P ＜ 0.01;WMD =-1.80,95％ CI (-2.20,-1.50),P ＜0.01],improve the clinical efficiency of [OR =4.78,95％ Cl (3.54,6.47),P ＜ 0.01] display.Blood lipid and cardiac ultrasound index show that atorvastatin combined with trimetazidine can better improve the patient's LVEDD [WMD =-2.69,95％ CI (-4.39,-0.98),P ＜ 0.01] LVESD [WMD =-6.92,95 ％ CI(-11.82,-2.02),P ＜ 0.01].The decrease of serum level of TC,TG,LDL-C was better than atorvastatin monotherapy,but there were no statistically significant differences in the improvement level of serum HDL-C in the included patients (P =O.17).In the included studies,atorvastatin combined with trimetazidine can effectively reduce the incidence of adverse reactions in patients [0R=0.33,95％ CI (0.13,0.85),P=0.02].Conclusions Atorvastatin combined with trimetazidine is safer and more effective than atorvastatin alone in the treatment of coronary heart disease angina pectoris.

Effect of trimetazidine on expression of HSP70 and Mn-SOD after myocardial ischemia/reperfusion in rats / 中华老年心脑血管病杂志

Objective To study the protective effect of trimetazidine pretreatment on myocardial I/R in a rat I/R model and its mechanism.Methods One hundred and twenty SD rats were divided into control group,I/R group,HSP70 inhibitor group,trimetazidine treatment group and combined treatment group (24 in each group).The rats in each group were further divided into 30 min reperfusion group,4 h reperfusion group and 8 h reperfusion group (8 in each group).Their HSP70-positive myocardial cells were calculated,their serum CK,CK-MB,MDA,SOD levels and their myocardial infarction size were measured.Results The serum CK and CK-MB levels were significantly higher in I/R group,HSP70 inhibitor group,trimetazidine treatment group and combined treatment group than in control group and were significantly lower in trimetazidine treatment group than in combined treatment group and I/R group after reperfusion for 4 and 8 h (P＜0.01).The serum levels of HSP70 and SOD were significantly higher,the MDA levels were significantly lower in trimetazidine treatment group than in combined treatment group and I/R group after reperfusion for 30 min,4 and 8 h (P＜0.01).The infraction size was significantly smaller in trimetazidine treatment group than in combined treatment group and I/R group after reperfusion for 4 and 8 h (P＜0.05).Conclusion Trimetazidine can increase the serum HSP70 level in myocardial cells,reduce the infarction size,and protect the myocardium against I/R in rats.

Effects of Trimetazidine on Myocardial Remodeling and Oxidative Stress in Patients with Hypertensive Heart Disease / 中国药房

OBJECTIVE:To prospectively study the effects of trimetazidine on myocardial remodeling and oxidative stress in patients with hypertensive heart disease (HHD),in order to provide reference for clinical treatment of HHD.METHODS:Eighty-two HHD patients were selected from our hospital during Jan.2014-Jul.2016,and they were divided into control group and observation group by sortition randomization method,with 41 cases in each group.Control group received routine HHD chemical drug (antihypertensive drugs,lipid-lowering drugs,hypoglycemic agents and antiplatelet drugs,etc.) therapy.Observation group was additionally given trimetazidine 20 mg,tid,on the basis of control group.Both groups were treated for 3 months.Before treatment and after 3 months of treatment,SBP,DBP,New York Heart Association (NYHA) cardiac function grade,LVEF,LVESD,LVEDD,LVMI and the levels of GSH-Px,SOD,MDA and ROS were compared between 2 group.The occurrence of ADR was observed in 2 groups.RESULTS:Before treatment,there was no statistical significance in each index between 2 groups (P＞0.05).After 3 months of treatment,SBP and DBP of 2 groups were decreased significantly compared to before treatment (P＜0.01);there was no statistical significance between 2 groups (P＞0.05).There was no statistical significance in NYHA cardiac function grade compared to before treatment or between 2 groups (P＞0.05).LVESD,LVEDD and LVMI of observation group were decreased significantly compared to before treatment (P＜0.05);LVEF was increased significantly compared to before treatment (P＜0.05);LVEDD and LVMI of observation group were significantly lower than control group (P＜0.05).Compared to before treatment,SOD level of control group was decreased significantly,while the levels of GSH-Px and SOD in observation group were increased significantly;MDA and ROS of observation group were significantly lower than those of control group,with statistical significance (P＜0.05).No obvious ADR was found in 2 groups.CONCLUSIONS:Trimetazidine can improve cayocardial remodeling and reduce oxidative stress level of HHD patients with good safety.

The Preventive Effects of Combined Nicorandil With Trimetazidine on Contrast-induced Nephrophathy in Patients Undergoing Elective Percutaneous Coronary Intervention / 中国循环杂志

Objectives: To observe the preventive effects of combined nicorandil with trimetazidine strategy on contrast-induced nephrophathy in patients undergoing elective percutaneous coronary intervention (PCI). Methods: 521 patients with acute coronary syndrome undergoing elective PCI were randomly divided into 4 groups:control group (n=208), nicorandil group (n=105), trimetazidine group (n=104), nicorandil plus trimetazidine group (n=104). The control group received hydration and aspirin, β-blockers, statins and other conventional drugs for coronary heart disease. The remaining three groups were given respective medication on top of the medications used in control group at 48 hours prior to PCI. The levels of respective blood index were measured and compared among four groups at preoperative and at 72 hours post operation. The primary endpoint was the incidence of CIN. Results: The incidence of contrast-induced nephropathy (CIN) in the control group, nicorandil group, trimetazidine group, nicorandil plus trimetazidine group were 8.2%, 2.8%, 3.8%, 1.0% respectively, which was significantly lower in nicorandil plus trimetazidine group than in the control group (P=0.009). Multivariate logistic regression analysis showed that, compared with control group, the use of nicorandil plus trimetazidine strategy was related to decreased CIN incidence (OR=0.114, 95%CI: 0.015-0.880, P=0.037). Conclusions: In patients with acute coronary syndrome undergoing elective PCI, the use of nicorandil plus trimetazidine strategy is related to decreased CIN incidence.