Perindopril Group Research Articles

Comparison of Adverse Events between Ramipril and Perindopril in Contemporary Cardiac Practice

Background: Angiotensin-converting enzyme inhibitors (ACEIs) are extensively used for the treatment and management of cardiovascular diseases. Although ACEIs are a well-tolerated medication in high percentage of patients, around 30% can develop adverse reactions like dry cough. Objective: The objective of the study was to capture the incidence of cough in patients with cardiovascular diseases that were prescribed with perindopril and ramipril in an Indian tertiary care hospital. Methods: In this observational study, the incidence of cough in patients with cardiovascular diseases that were prescribed with perindopril and ramipril was estimated. Results: A total of 223 patients were enrolled in this study. Around 50.67% patients received ramipril; among them, 6.02% received 1.25 mg, 78.95% received 2.5 mg, and 13.53% received 5 mg of ramipril. Around 35.9% (n = 80) patients received perindopril. In perindopril group, 31.3% of the patients received 2 mg dose and 68.8% of patients received 4 mg dose. Among perindopril group, the incidence of cough was observed in 10% (n = 8) of the patients, whereas in ramipril group, it was 19.55% (P = 0.00136). Due to cough, in perindopril group, 6.3% (5/80) of the patients discontinued treatment whereas in ramipril group, 9% (12/133) of the patients discontinued treatment medication. Conclusions: Our study has demonstrated that perindopril has been associated with a relatively low incidence of cough compared to ramipril.

LuQi Formula Regulates NLRP3 Inflammasome to Relieve Myocardial-Infarction-Induced Cardiac Remodeling in Mice.

Background Excessive activation of the nod-like receptor family pyrin domain containing 3(NLRP3) inflammasome plays a significant role in the progression of cardiac injury. In China, it has been well recognized that Chinese herbal medicine is markedly effective in treating cardiovascular diseases (CVDs). LuQi Formula (LQF) has been used clinically for more than 10 years and confirmed to be effective in improving cardiac function and inhibiting apoptosis. However, the specific mechanisms underlying its efficacy are mostly unknown. This study aimed to evaluate whether LQF could alleviate cardiac injury and apoptosis by regulating the NLRP3 inflammasome and the caspase-3/Bax pathway. Purpose In this study, we investigated the effects of LQF on cardiac remodeling in a mouse model of myocardial infarction (MI) in vivo. Methods Forty male C57BL/6 mice were randomly divided into four groups: the sham group, the model group, the LQF group, and the perindopril group, with a sample size (n) of 10 mice in each group. Except the sham group, the other groups received left anterior descending (LAD) coronary artery ligation to induce MI and then treated with LQF, perindopril, or saline. Six weeks after MI, echocardiography was used to evaluate cardiac structure and function. Myocardial tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson's trichrome to analyse myocardial fibrosis. Myocardial hypertrophy was observed by fluorescent wheat germ agglutinin (WGA) staining. The expressions of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, Bcl-2, and Bax in heart tissues were assessed by western blot analysis. mRNA expressions of ANP and BNP in heart tissues were measured by RT-PCR. The expression of reactive oxygen species in myocardial tissue was detected by using a DCFH-DA probe. Results Echocardiographic analysis showed that compared with the model group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the LQF and perindopril group were increased (P < 0.05), left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end-systole (LVIDs) were reduced (P < 0.05), and H&E and Masson's trichrome staining of cardiac tissues showed that LQF and perindopril could partially reverse ventricular remodeling and alleviate myocardial fibrosis (P < 0.05). WGA fluorescence results showed that compared with the model group, myocardial hypertrophy was significantly reduced in the LQF and perindopril group. We also found that LQF and perindopril reduce the oxidative stress response in the heart of MI mice. The protein expression of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, and Bax was downregulated in the LHF and perindopril treatment group, and Bcl-2 expression was upregulated. Conclusion LQF and perindopril significantly attenuated cardiac injury and apoptosis in the MI model. In addition, we found that LQF effectively inhibited the activation of the NLRP3/ASC/caspase-1/IL-1β cascade, decreased inflammatory infiltration, delayed ventricular remodeling, and downregulated caspase-3/Bax signaling, which can effectively reduce the apoptosis of cardiomyocytes. Perindopril showed the same mechanism.

Effect of Perindopril on Atrial Fibrillation Recurrence and Burden: Results of the Canadian Trial of Atrial Fibrillation (CTAF)-2

BackgroundHypertension is a risk factor for the development and exacerbation of atrial fibrillation (AF). Angiotensin-converting enzyme inhibitors are a standard-of-care treatment option for patients with hypertension; however, there is conflicting evidence about their effects on AF recurrence. Therefore, our objective was to assess the efficacy of perindopril, compared with placebo, to reduce AF recurrence in patients with hypertension and AF. MethodsIn a multicenter, double-blind, placebo-controlled trial, patients with hypertension and symptomatic AF were randomly assigned (1:1) to perindopril or placebo based on a stratification factor of antiarrhythmic drug use. Patients with terminated AF were followed up from 30 days after randomization to 7 to 13 months. The primary endpoint was AF recurrence. Secondary endpoints included AF hospitalization, cardioversion, and blood pressure control. Recurrent events, AF burden, and safety endpoints were also investigated. ResultsA total of 315 patients were randomly assigned, and 301 patients were included in the modified intent-to-treat analysis (155 vs 146 patients in the perindopril and placebo groups, respectively). The mean follow-up was 336 ± 70 days, and 91.1% of patients were compliant to the treatment medication throughout the study. After adjustment for baseline antiarrhythmic drugs, there was no statistically significant difference in the hazards of AF recurrence (hazard ratio, 1.22; 95% confidence interval, 0.92-1.61), with similar blood pressure. The incidence of secondary endpoints and adverse events also did not differ between treatment arms. ConclusionsPerindopril does not reduce recurrence or the number of AF episodes in patients with hypertension and AF.

Cardioprotective effect of Yiqi Huoxue granule through regulation of mitophagy after myocardial infarction in rats

To investigate the cardioprotective effect of Yiqi Huoxue granule (YQHXG) in the regulation of autophagy in rats induced with myocardial infarction (MI). An acute MI animal model was established by ligation of the left anterior descending branch of the coronary artery in Sprague-Dawley rats. Besides, 20 rats received sham operation were classified into a control group. The remaining 59 rats were randomly divided into MI model group (n = 19), YQHXG group (n = 20), and perindopril group (n = 20). Relevant indicators on days 7 and 28 were observed in each group. Left ventricular function was determined by echocardiography. The structure and morphology of mitochondria, and the number of autophagic vesicles, were observed by transmission electron microscopy. The mRNA and protein expression levels of LC3, FUNDC1, Beclin-1, and BNIP3 were examined in the tissue of the MI marginal area. Compared with the MI model group, YQHXG showed obvious improvements in cardiac functions. Observing the microscopic morphology of the heart tissue, myocardial tissue damage attenuated, autophagic signs of autophagosomes and autolysosomes reduced, vacuolization in mitochondria mitigated, and mitochondria arranged in order. YQHXG could reduce the degree of tissue lesion after MI and regulate the expression of autophagy-related molecules at different stages. On Day 7, YQHXG significantly downregulated the expression of Fundc1 , Becn1 , Bnip3 mRNA and reduced the levels of FUNDC1, Beclin-1, BNIP3, and LC3 B proteins expression (all P < .001). On Day 28, YQHXG could upregulate the expression of Becn1 , Fundc1 and Bnip3 mRNA and increased the levels of the corresponding proteins expression (all P < .001). Besides, it also increased LC3 B protein expression level ( P = . 0344). YQHXG regulated the expression of mitochondrial autophagy-related factors in myocardial tissue and mitochondrial autophagic activity at different stages to protect the heart following MI.

IMPACT OF DIFFERENT ANGIOTENSIN-CONVERTING INHIBITORS ON OUTCOMES OF POST-MYOCARDIAL INFARCTION PATIENTS

The aim: To compare the long-term effects of different angiotensin-converting enzyme inhibitors in post-myocardial infarction (MI) patients. Materials and methods: Of 445 consecutive patients with myocardial infarction, 76 (17%) patients had co-morbid conditions, as well as were found to be compliant with secondary prevention treatment and eligible for follow-up. These patients were assigned to ramipril, perindopril or zofenopril groups in complex management of post-MI period. Subsequently, the patients were followed-up prospectively for a period of up to 24 months. Results: Patients of zofenopril group performed better in terms of post-MI biventricular remodeling and left ventricular function recovery. Also, patients receiving zofenopril showed benefits in terms of short-term and long-term mortality as compared with patients of ramipril and perindopril groups. Conclusion: Zofenopril may have advantages over perindopril and ramipril in the complex management of post-MI patients in terms of prevention of negative myocardial remodeling, onset of congestive heart failure and major adverse events.

Luhong Formula Has a Cardioprotective Effect on Left Ventricular Remodeling in Pressure-Overloaded Rats.

Background Luhong formula (LHF)—a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd—is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis. Methods Forty-eight SD male rats were randomly assigned into six groups (n = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-β1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-β1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope. Results LHF significantly lowered the rat's HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-β1, caspase-3, VEGF, and VEGFR2 expression. Conclusion LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-β1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.

Anti-Depressant and Neuroprotective Effects of Captopril and Perindopril in Paraquat Model of Parkinsonism

Non-motor symptoms such as depression, dementia, autonomic nervous system problems may be more evident in the later part of Parkinsonism. L-dopa is largely ineffective for non-motor symptoms. The objective of the present study was to evaluate the anti-depressant and neuroprotective role of captopril and perindopril in paraquat mice model of Parkinsonism. Adult Swiss albino mice were divided into five groups of six each. Parkinsonism was induced with paraquat (7mg/kg bodyweight at an interval of 2 days) in four groups. Experimental group was treated with captopril (20mg/kg intraperitoneal) and perindopril (5mg/kg intraperitoneal). Depression influences on behaviour was studied with forced swim test and tail suspension test. Oxidative stress markers – glutathione, lipid peroxidation assay, myeloperoxidase activity, catalase, superoxide dismutase, monoamine oxidase A and B are carried out in one hemisection of the mice brain to evaluate the neuroprotective role of the test drugs. The test group mice exposed to captopril and perindopril had significantly less immobility time in both forced swim test and tail suspension test in comparison to the paraquat group, indicating anti-depressant effects of these drugs. Lipid peroxidation, myeloperoxidase activity, catalase, superoxide dismutase, monoamine oxidase B levels were significantly increased in both captopril and perindopril groups in comparison to the control group. Captopril and perindopril have shown beneficial effects for depression (as evidenced through forced swimming test and tail suspension test) in paraquat model of Parkinsonism. These drugs reduce the oxidative stress in paraquat mice model of Parkinsonism

Effects of Phytochemicals on Blood Pressure and Neuroprotection Mediated Via Brain Renin-Angiotensin System.

Background: The renin-angiotensin system (RAS) in the brain plays a crucial role in maintaining blood pressure as well as neuroprotection. This study compared the effects of curcumin, quercetin, and saponin on blood pressure, the brain RAS, and cholinergic system using perindopril, an angiotensin converting enzyme inhibitor (ACEI), as a positive control. Methods: Five-week-old male mice were stabilized and randomly assigned into a control group (n = 8), three phytochemical-treated groups (curcumin (n = 8), quercetin (n = 8), and saponin (n = 8)), and a positive control group (n = 8). The groups treated with the phytochemical were orally administered daily at a dose of 50 mg/kg body weight of phytochemicals. During the experiments, the weight and dietary intakes were measured regularly. After experiments, the brain tissue was homogenized and centrifuged for an additional assay. The concentrations of ACE, angiotensin II (AngII), and aldosterone levels were measured, and the mRNA expressions of renin and ACE were measured. As biomarkers of neuroprotection, the concentrations of acetylcholine (ACh) as well as the concentration and activity of acetylcholine esterase (AChE) were measured. Results: After 4 weeks of treatment, the perindopril group showed the lowest blood pressure. Among the groups treated with the phytochemicals, treatment with curcumin and saponin significantly reduced blood pressure, although such effect was not as high as that of perindopril. Among phytochemicals, curcumin treatment significantly inhibited the concentration and activity of ACE, concentration of AngII, and mRNA expression of ACE. All phytochemical treatments significantly increased the concentration of ACh. The levels of AChE activity in groups exposed to curcumin or saponin (not quercetin) were significantly inhibited, Conclusion: Curcumin administration in rats reduced blood pressure by blocking the brain RAS components and protected the cholinergic system in brain by inhibiting the activity of AChE.

The effect of perindopril on echocardiographic parameters, NYHA functional class and serum NT-proBNP values in patients with diastolic heart failure.

Growing evidence has demonstrated that diastolic heart failure occurs in about half of heart failure (HF) patients. We investigated the effects of perindopril on echocardiographic parameters, New York Heart Association (NYHA) functional class and serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in patients with diastolic heart failure. In total, 108 diastolic heart failure patients aged ≥ 50 years, who had diastolic dysfunction with an ejection fraction ≥ 50%, were enrolled and randomised to one of the two study groups. Perindopril was initiated in the study group and the control group was given standard therapy. Echocardiographic parameters, NT-proBNP levels and NYHA classes were recorded. The patients were followed for 11 (three to 16) months. Eighty-eight patients completed the study. Although diastolic parameters were not changed, A' (septal) velocity (10.8 vs 9.9 cm/s) and Sm (septal) velocity (8.5 vs 7.6 cm/s) were significantly increased in the perindopril compared to the control group. A significant increase in A' (septal) velocity (+0.61 vs -0.28 cm/s, p = 0.04) and a slight increase in Sm (septal) velocity (+0.99 vs 0.36 cm/s, p = 0.054) were noted in the perindopril group. Tissue Doppler septal late diastolic velocities and septal systolic myocardial velocities increased in the perindopril group but NT-proBNP levels, and NYHA class was not changed in this study population.

Perindopril inhibits myocardial apoptosis in mice with acute myocardial infarction through TLR4/NF-κB pathway.

To explore the anti-apoptotic effect of perindopril on myocardial cells in mice with acute myocardial infarction (AMI). A total of 48 mice were randomly divided into 4 groups before intervention, namely sham operation group (Sham group, n=12), AMI group (n=12), 1.5 mg/kg perindopril treatment group (Perindopril group, n=12), and 1.5 mg/kg perindopril treatment and Toll-like receptor-4 (TLR4) knockout group (TLR4-/-Perindopril group, n=12). Mice in the control group and AMI group were gavaged with normal saline, and those in the Perindopril group and TLR4-/-Perindopril group were gavaged with perindopril for 7 d. On the 4th day after drug administration, mice in the AMI group, Perindopril group and TLR4-/-Perindopril group were subjected to the ligation of the anterior descending coronary artery to induce AMI, and those in the Sham group underwent the same operation, but had a loose knot at the anterior descending coronary artery. At 24 h after the above operation, color echocardiography was performed on mice to observe changes in cardiac function. Then, the mice were sacrificed. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) assay was carried out to determine myocardial apoptosis. Immunohistochemistry and Western blotting technique were employed to detect the protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p50 in infarction zones. The messenger ribonucleic acid (mRNA) expression levels of TLR4 and NF-κB p50 in infarction zones were measured via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Perindopril could significantly reduce the number of apoptotic myocardial cells after AMI. Mouse echocardiography showed that ejection fraction (EF), left ventricular fractional shortening (FS), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) of AMI mice in the Perindopril groups were markedly superior to those in the AMI group. AMI mice in the Perindopril group had decreased expression levels of Bax protein and TLR4 and NF-κB p50 mRNA and protein, as well as the Bax/Bcl-2 ratio. Knockout of TLR4 attenuated the effect of perindopril in alleviating myocardial apoptosis after AMI. Perindopril inhibits myocardial apoptosis in mice with AMI through the TLR4/NF-κB pathway.

Effects of perindopril on bone turnover markers and bone mineral density in osteoporotic rats

Objective To explore the effects of peridopril on osteoporosis and possible mechanisms involved. Methods Fifty experimental rats were divided into a normal control group, a sham operation group(Sham group), an ovariectomized group(OVX group), a perindopril group and an estrogen group(E2 group), with ten in each group.The perindopril group was intragastrically administered perindopril 4 mg/kg per day, the E2 group was intragastrically administered estrogen 1.2 mg/kg per day, and rats in the normal control group, the sham group and the OVX group were intragastrically given an equal volume of distilled water.Drugs were given once a day for 12 weeks.After 12 weeks of drug intervention, all rats were anaesthetized and 12 ml blood was extracted from the heart, and serum calcium, phosphorus, alkaline phosphatase(ALP)and tartrate-resistant acid phosphatase(TRACP)were determined by enzyme-linked immunosorbent assays.The bone mineral density(BMD)of the left femur was measured by dual energy X-ray absorptiometry. Results After 4 weeks of drug intervention, the femur BMD was lower in the OVX group than in the sham operation group and the normal control group(F=12.224, P 0.05). After 12 weeks of drug intervention, serum Ca and P levels had no significant difference between the groups(P>0.05). ALP and TRACP levels in the OVX group were (192.30±14.50) U/L and (12.7±1.72) U/L, respectively, which were significantly higher than those in the sham operation group(P<0.01). ALP and TRACP levels in the perindopril group were (169.00±10.14) U/L and (10.19±1.24) U/L, respectively, which were lower than those in the OVX group(P<0.05). ALP and TRACP levels in the E2 group were (130.76±9.47) U/L and (7.04±0.96) U/L, respectively, which were lower than those in the OVX group(P<0.01). BMD in the OVX group was (0.161±0.011) g/cm2, which was lower than that in the sham operation group(P<0.01). BMD in the perindopril group was (0.173±0.011) g/cm2, which was higher than that in the OVX group(P<0.05). After estrogen treatment, BMD of the E2 group was (0.196±0.008) g/cm2, which was higher than that in the OVX group(P<0.01). Conclusions Perindopril can decrease high bone turnover, increase bone density in ovariectomized rats, and thus may be used for alleviating postmenopausal osteoporosis. Key words: Perindopril; Osteoporosis; Bone density; Alkaline phosphatase

Perindopril and a Galectin-3 Inhibitor Improve Ischemic Heart Failure in Rabbits by Reducing Gal-3 Expression and Myocardial Fibrosis.

Objective: Ventricular remodeling is considered the basis of heart failure and is involved in myocardial fibrosis. This study aimed to assess perindopril and a galectin-3 inhibitor (modified citrus pectin, MCP) for their effects on ventricular remodeling and myocardial fibrosis in rabbits with ischemic heart failure.Methods: Rabbits were divided into sham, heart failure (model), MCP, and perindopril groups, respectively. A rabbit model of ischemic heart failure was established by ligating the anterior descending coronary artery. Then, the rabbits were orally administered MCP, perindopril, or saline (all at 2 ml/kg/d) for 4 weeks. Sham animals only underwent open heart surgery without further treatment. After 4 weeks, cardiac function was examined by ultrasound, and myocardial Gal-3, collagen type I, and collagen type III expression was assessed, at the gene and protein levels, by real-time PCR and Western-Blot, respectively; serum Gal-3 was detected by ELISA, and fibrosis in the infarct zone was evaluated by H&E and Masson staining.Results: In model animals, myocardial Gal-3, collagen type I, and collagen type III gene and protein expression levels were increased compared with control values, as well as serum Gal-3 amounts. Treatment with perindopril and MCP significantly alleviated the above effects, with no significant differences between the treatment groups. Pathological analyses showed that compared with model animals, treatment with MCP or perindopril resulted in relatively neatly arranged myocardial cells in the infarct zone, with significantly decreased fibrosis.Conclusion: Perindopril and the galectin-3 inhibitor MCP comparably improve ischemic heart failure in rabbits, by downregulating Gal-3 and reducing myocardial fibrosis.

A comparison of the effects of perindopril arginine and amlodipine on choroidal thickness in patients with primary hypertension

This study aimed to investigate the effects of two different medical treatment options on choroidal thickness (CT) in patients with primary hypertension. Forty newly diagnosed primary hypertension patients and 21 healthy volunteers were included. The patients were randomly divided into two subgroups. Group I started on perindopril arginine and Group II started on amlodipine. Submacular CT using optical coherence tomography (OCT) was measured before treatment and at the third and sixth months after treatment. Initial mean arterial pressure (MAP) values in Groups I and II and the control group were 113.4, 109.8, and 89.4 mmHg, respectively, and mean CT values were 257.9, 286.5, and 300.9 μm. Mean MAP values in Groups I and II and the control group at the sixth month after treatment were 99.7, 99.6, and 90.2 mmHg, respectively, and mean CT values were 293.1, 286, and 297.4 μm. Analysis of the changes occurring during the study revealed significant variation in MAP in Groups I and II, and in CT in Group I only. A gradual increase in CT developed with perindopril arginine therapy in patients with primary hypertension, while no significant change occurred in CT in the amlodipine group.

Effect of Shenqi Yangxin decoction on high mobility group box 1 and inflammatory signal pathway in a rat model of dilated cardiomyopathy

OBJECTIVETo investigate the effects of Shenqi Yangxin decoction (SQYXD) on heart function in a rat model of dilated cardiomyopathy (DCM) and its potential mechanisms. METHODSSprague-Dawley rats were randomly divided into normal (10 rats) and DCM (150 rats) groups. DCM was induced by an intraperitoneal injection of adriamycin. Then, DCM baseline group was randomly selected sixteen DCM rats. The remaining DCM rats were randomly divided into DCM control, perindopril, metoprolol, and SQYXD groups. Cardiac function and histological analysis plus biochemical measurement of serum levels of brain natriuretic peptide (BNP), and inflammatory factors were measured. The mRNA and protein expression levels of high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR-4), receptor for advanced glycation end products (RAGE), and nuclear factor-κB (NF-κB) were determined. Myocardial metabolism imaging was performed on the normal, SQYXD and DCM control groups to evaluate the effectiveness of treatments. RESULTSRats in the DCM control group exhibited dilated left ventricular diameter, impaired cardiac function, disorganized sarcomere, impaired glucose metabolism, increased heart weight index, and increased levels of BNP, which were improved by treatment with SQYXD. In addition, hearts from rats in the DCM baseline group exhibited significantly higher levels of HMGB1, TLR-4, RAGE, NF-κB, tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-10, compared with the normal group. Interestingly, the mRNA level of HMGB1 in the DCM baseline group was positively correlated with that of TLR-4, RAGE, NF-κB, BNP, and LVEDD, but negatively correlated with LVEF. SQYXD inhibited the upregulation of HMGB1 expression and its downstream inflammatory factors. CONCLUSIONShenqi Yangxin decoction effectively reduced the dilated left ventricular diameter and improved heart function in dilated cardiomyopathy. The mechanisms underlying the action on DCM involve regulating the gene and protein expression of HMGB1 and its inflammatory signal pathways in the DCM rat model.

A PROSPECTIVE CLINICALTRIAL OF AMLODIPINE IN COMPARISON TO PERINDOPRIL

Objective: The objective of this research was to perform a prospective clinical trial to compare antihypertensive effects of amlodipine and perindopril in hypertensive patients.Methods: In our study, we compared antihypertensive effects of well tolerated and commonly used antihypertensive drugs, amlodipine and perindopril. There were 81 hypertensive patients of both sexes over 40 y of age without other diseases included in this prospective clinical trial. Forty (40) patients were treated with amlodipine (5 mg/day) and forty-one (41) patients were treated with perindopril (4 mg/day). After one month of taking both drugs, blood pressure was measured in the supine position with a standard mercury sphygmomanometer in the morning.Results: Amlodipine and perindopril groups were having almost similar characteristics at the beginning of the study. There was significantly decrease insystolic blood pressure (sBP) throughout the study period in the amlodipine group (p≤ 0.05) but not in the perindopril group. The efficacy of amlodipine over perindopril on systolic blood pressure and diastolic blood pressure (dBP) was significant (p≤ 0.001 for sBP and p≤ 0.05 for dBP).Conclusion: It may be concluded that the antihypertensive efficacy of amlodipine was superior when compared to perindopril.

Yiqi Huoxue prescription can prevent and treat post-MI myocardial remodeling through promoting the expression of AMPK signal pathway

ObjectiveTo investigate how Yiqi Huoxue (YQHX) prescription regulates mitochondrial biosynthesis and ATP synthesis via AMP-activated protein kinase (AMPK) and to reveal its molecular mechanism in preventing and treating post-MI myocardial remodeling. MethodsThe MI animal model of myocardial infarction were established by ligating Sprague Dawley (SD) rats' left anterior descending coronary arteries; the animals were randomly divided into MI group, YQHX prescription group and perindopril group, and a sham operation group was set at the same time. Related drug intervention was administered on the 2nd day after surgery, the YQHX group was given Astragalus, angelica, ginseng, Ligusticum wallichii and pseudoginseng, provided by the Dongzhimen Hospital of Beijing University of Chinese Medicine, once per day, at a dose of 21 g/kg body weight/day (the clinical equivalent dose based on a previous study), and the changes in relevant indicators were observed at 1 week and 4 weeks. Echocardiography (ECG) was used to observe the changes in rat cardiac structure and functions; the morphology-based technique was used to observe the changes in myocardial cells and mitochondria; the expression of AMPK signal pathway-related proteins and mRNA was detected using western blotting and real-time fluorescence quantification respectively, while fluorescence enzyme-labeled method was used for detecting ATP synthesis. ResultsCardiac structure and functions: Compared with the MI group at 1 week, the YQHX prescription group and the perindopril group exhibited increased LVEF and LVFS (Pall < .05); their LVEDs and LVEDd were reduced but suggested no statistically significant differences (F = 2.258, F = 0.3464, Pall > .05). At 4 weeks, both LVEF and LVFS were elevated in the YQHX prescription group (P = .008, .009) and the perindopril group (P = .279, .333), where differences in the later group indicated no statistical significance; the YQHX prescription group and the perindopril group were also featured by reduced LVEDs and LVEDd (Pall < .05). Morphology: Compared with the MI group at two time nodes, the YQHX prescription group and the perindopril group exhibited significant improvement in the pathological changes in myocardial cells and mitochondrial structure. Expression of AMPK signal pathway-related proteins and mRNA: The expression of both pLKB1 and pAMPK proteins followed a rising trend in the YQHX prescription group and the perindopril group at 1 week. The expression of LKB1mRNA and AMPKmRNA was elevated (Pall < .05). The increased expression of PGC-1α, NRF1 and mtTFA proteins demonstrated statistically significant differences (Pall < .05). The expression of mtDNA protein followed an increasing trend. At 4 weeks, the expression of both pLKB1 and pAMPK proteins was elevated (Pall < .05). Heightened expression was also reported in LKB1mRNA and AMPKmRNA (Pall < .05). The increased expression of PGC-1α, NRF1, mtTFA and mtDNA proteins demonstrated statistically significant differences (Pall < .05). ATP synthesis: ATP synthesis was increased in the YQHX prescription group and the perindopril group at both 1 week and 4 weeks (Pall < .001). ConclusionThe possible mechanism of YQHX prescription for preventing and treating post-MI myocardial remodeling may function through strengthening the activation AMPK signal pathway by LKB1, thus further increasing the expression of downstream transcription factor proteins and initiating mitochondrial replication and transcription; as a result, the YQHX prescription can improve the post-MI damage in mitochondrial morphological structure in the tissue at heart marginal zone as well as enhance mitochondrial biosynthesis and ATP synthesis.

Effect of Yiqihuoxue prescription on myocardial energy metabolism after myocardial infarction via cross talk of liver kinase B1-dependent Notch1 and adenosine 5′-monophosphate-activated protein kinase

ObjectiveTo investigate the effect of Yiqihuoxue prescription (YQHX) from Traditional Chinese Medicine (TCM) on myocardial glucose and lipid metabolism after myocardial infarction via the cross talk between the liver kinase B1 (LKB1)-dependent Notch1 and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). YQHX was prepared with substances with properties that benefit, to activate blood circulation based on the TCM theory. MethodsAnimal models of myocardial infarction were established by ligating Sprague Dawley rats' left anterior descending coronary arteries. The animals were randomly divided into a myocardial infarction (MI) group, a YQHX group, a perindopril group, a γ-secretase inhibitor, Notch signal inhibitor (DAPT) group, a DAPT+YQHX group and a sham group. The related drugs were administered on the second day after operation, and changes in the relevant indexes were examined on weeks 1 and 4. Changes in cardiac structure and function were examined by echocardiography. The glucose and free fatty acids (FFA) were examined by ELISA. The expression of Notch, LKB1 and AMPK mRNA was examined by a real-time fluorescence quantitative method. The expression of glucose transporter 4 (GLUT4), and the expression of total acetyl-CoA carboxylase (ACC) and its phosphorylation were examined by western blotting. ResultsCompared with the sham group, the expression of Notch, LKB1 and AMPK mRNA in the MI group was lower. Compared with the MI group, the expression of these mRNAs in the YQHX and perindopril groups was higher, and their expression in the DAPT group was lower. At all time points, the protein expression of GLUT4 and pACC decreased in the MI group. On week 1, the expression of pACC protein was higher. In the DAPT group, the expression of pACC protein decreased. Compared with the YQHX group, the expression of pACC protein in the DAPT + YQHX group was lower. On week 4, compared with the MI group, the expression of GLUT4 protein in the YQHX group and the perindopril group was higher. The expression of GLUT4 protein in the DAPT group decreased. Compared with the YQHX group, the expression of GLUT4 protein in the DAPT+YQHX group was lower. There was no significant difference in the expression of ACC protein between the groups. ConclusionYQHX promoted cross talk between the LKB1-dependent Notch1 and AMPK in myocardial tissue after myocardial infarction. Furthermore, it regulated the glucose and lipid metabolism of cardiomyocytes at different time points, thereby ameliorating the cardiac energy metabolism via different mechanisms and protecting the heart.

ROLE OF GENDER SPECIFICS IN MYOCARDIAL REMODELLING, CARDIOVASCULAR COMPLICATIONS DEVELOPMENT AND EFFICACY OF PHARMACOTHERAPY IN HEART FAILURE PATIENTS AFTER CARDIAC SURGERY

Aim. To assess gender influence on myocardial remodelling, pharmacotherapy efficacy and complications development in chronic heart failure patients (CHF) post cardiac surgery. Material and methods. In the study, 87 patients included, both genders, with CHF, who had been planned for cardiac surgery. All underwent standard investigations and CHF treatment, as other pathologies. Myocardium specimens from the right atrium appendage (RAA) were collected during surgery, investigated with general histology, immune histochemistry (expression of MMP-9, TIMP-1 and р38αMAPK) methods. For the evaluation of treatment influence on myocardium, intervention groups were selected: enalapril and metoprolol, perindopril and amlodipine (Prestance®, “Les Laboratoires Servier”, France). In all participants, at 10-14 day post surgery, the rate of complications was evaluated, by groups. At least one complication led to selection the participant as adverse in-hospital outcome. The relations were studied, of post-surgery complications with EchoCG data and morphological changes in LAA myocardium, taken the gender and left ventricle ejection fraction (LVEF). Results. In cardiac surgery group with heart failure and preserved LVEF (HFpEF) with the increase of CHF functional class, normal LVEF remained, and there was worsening of the LV diastolic function. In HFpEF males there was decrease of EF with transition to “grey zone” by III functional class, and eccentric remodeling predominated with unchanged diastolic function. In HF mid-range EF group, regardless of gender, there was eccentric LV remodelling. In RAA myocardium of women there was lower grade of myocardial fibrosis and mononuclear areas of infiltration, and there was higher rate of cardiovascular as extracardiac complications. High grade of MMP-9 in RAA revealed in the group of HF mid-range EF and adverse outcome, regardless gender, and increased expression of р38αMAPK in females of thisgroup. In perindopril and amlodipine group there was lower grade of MMP-9 and р38αMAPK expression. Conclusion . The study demonstrated gender differences in remodelling of myocardium in HFpEF patients. This makes to consider female gender, HF midrange EF, MMP-9 expression in RAA myocardium, as prognostic markers of surgery adverse outcome. Combination of perindopril and amlodipine demonstrated protective influence on myocardium, with more prominent effect in females.

Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research (MANTICORE 101-Breast): A Randomized Trial for the Prevention of Trastuzumab-Associated Cardiotoxicity.

Purpose The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2-overexpressing (HER2-positive) breast cancer is dose-independent cardiac dysfunction. Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure. We hypothesized that angiotensin-converting enzyme inhibitors and β-blockers could prevent trastuzumab-related cardiotoxicity. Patients and Methods In this double-blinded, placebo-controlled trial, patients with HER2-positive early breast cancer were randomly assigned to receive treatment with perindopril, bisoprolol, or placebo (1:1:1) for the duration of trastuzumab adjuvant therapy. Patients underwent cardiac magnetic resonance imaging at baseline and post-cycle 17 for the determination of left ventricular volumes and left ventricular ejection fraction (LVEF). Cardiotoxicity was evaluated as the change in indexed left ventricular end diastolic volume and LVEF. Results Thirty-three patients received perindopril, 31 received bisoprolol, and 30 received placebo. Baseline demographic, cancer, and cardiovascular profiles were similar between groups. Study drugs were well tolerated with no serious adverse events. After 17 cycles of trastuzumab, indexed left ventricular end diastolic volume increased in patients treated with perindopril (+7 ± 14 mL/m2), bisoprolol (+8 mL ± 9 mL/m2), and placebo (+4 ± 11 mL/m2; P = .36). In secondary analyses, trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated patients (-1 ± 5%) relative to the perindopril (-3 ± 4%) and placebo (-5 ± 5%) groups ( P = .001). Perindopril and bisoprolol use were independent predictors of maintained LVEF on multivariable analysis. Conclusion Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy-related declines in LVEF; however, trastuzumab-mediated left ventricular remodeling-the primary outcome-was not prevented by these pharmacotherapies.

Perindopril for the prevention of atrial fibrillation recurrence after radiofrequency catheter ablation: One-year experience

Recurrence of atrial fibrillation (AF) after ablation is still high. Perindopril plays an essential role in AF induction and maintenance. We aimed to prove that perindopril (8 mg) could prevent recurrence after pulmonary vein isolation. Patients with paroxysmal AF who received radiofrequency ablation were randomized to a 3-month course of perindopril 8 mg once daily (perindopril group) or placebo (placebo group). Angiotensin-II (Ang-II) therapy and standard transthoracic echocardiography were performed. All 256patients with paroxysmal AF who received radiofrequency ablation were randomized. And we followed them for complete 1 year. The 3-month recurrence and the 1-year recurrence were compared between the 2 groups. The 3-month recurrence of AF was observed in 33 (26.19%) of 126 patients in the placebo group vs 19 (14.62%) of 130 patients who received perindopril 8 mg once daily (χ2, P = .021). One-year recurrence of AF was observed in 36 (28.5%) of 126 patients in the placebo group as compared with 21 (16.2%) of 130 patients who received perindopril after 1 year (P = .017). The κ value was 0.94 in the control group (P < .001) and 0.96 in the perindopril group (P < .001) between 3-month and 1-year recurrence. The Ang-II level was related to the left atrial distance with the reduction in AF recurrence (r = 0.17, P = .005 at 3 months; r = 0.25, P < .001 at 1 year). Perindopril is an effective and safe treatment for the prevention of AF recurrence after radiofrequency catheter ablation. This effect seems to be strongly associated with a significant decrease in Ang-II level and left atrial distance.