Antihypertensive effect of telmisartan versus perindopril in hypertensive patients.

OBJECTIVE: We performed this meta-analysis determining the antihypertensive effect of telmisartan versus perindopril in patients with essential hypertension. BACKGROUND: The comparison of antihypertensive effects between telmisartan and perindopril were controversial. METHODS: Pubmed, Web of Science, and Cochrane Central were searched for all published studies. RESULTS: The antihypertensive effects were assessed in 753 patients included in 7 trials with a mean follow-up of 20 ± 16 weeks. There was no significant difference between telmisartan and perindopril in reduction of systolic blood pressure (SBP, weighted mean differences (WMD) 0.02 (95% confidence interval (CI), ‒2.78, 2.81) mm Hg, p > 0.05). The reduction of diastolic BP (DBP) treated with telmisartan was greater than perindopril in these patients (WMD ‒2.05 (95% CI, ‒2.60, ‒1.49) mm Hg, p < 0.001). Considering the effects of different doses on BP reduction, a sub-analysis was performed. The reduction of DBP treated with 40 mg/day telmisartan was greater than 4‒5 mg/day perindopril (WMD ‒2.18 (95% CI, ‒2.83, ‒1.53) mm Hg, p 0.05). CONCLUSION: The reduction of DBP is greater treated with telmisartan than perindopril in patients with essential hypertension (Tab. 2, Fig. 4, Ref. 34). Text in PDF www.elis.sk Keywords: essential hypertension, blood pressure, telmisartan, perindopril, meta-analysis.

Intravascular Renal Denervation Reduces Ambulatory and Office Blood Pressure in Patients with Essential Hypertension: A Meta-Analysis of Randomized Sham-Controlled Trials.

BACKGROUND: This meta-analysis was designed to evaluate the antihypertensive efficacy of intravascular renal denervation (RDN) in patients with essential hypertension, especially to determine the magnitude of blood pressure (BP) reduction with RDN therapy using second-generation catheters. METHODS: PubMed was searched to identify randomized sham-controlled trials from inception through August 2021. The endpoints were changes in 24-h ambulatory BP or office BP. This meta-analysis was performed by calculating the weighted mean difference (WMD) with 95% confidence interval (CI) using the random-effects model when the I2 index was <50%. A fixed-effects model was used when the I2 index was ≥50%. RESULTS: A total of 1,297 patients were included in 8 randomized, sham-controlled trials in this meta-analysis. Intravascular RDN reduced 24-h ambulatory systolic BP (SBP) -3.02 (WMD, 95% CI: -4.95, -1.10, p < 0.01) and diastolic BP (DBP) -1.66 (WMD, 95% CI: -2.44, -0.88, p < 0.001) mm Hg, respectively. In the studies using first-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were -2.67 (95% CI: -5.08, -0.27; p < 0.05; I2 = 0%, p = 0.53) and -0.82 (95% CI: -2.19, 0.56; p > 0.05; I2 = 0%, p = 0.64) mm Hg. In the studies using second-generation catheters, the WMDs of 24-h ambulatory SBP and DBP changes between intravascular RDN and sham control were -3.14 (95% CI: -5.94, -0.33, p < 0.05; I2 = 71%, p = 0.008) and -2.06 (95% CI: -3.02, -1.11, p < 0.001; I2 = 50%, p = 0.09) mm Hg. Intravascular RDN using second-generation catheters reduced office SBP -6.30 (WMD, 95% CI: -7.67, -4.93, p < 0.001; I2 = 43%, p = 0.14) and DBP -3.88 (WMD, 95% CI: -4.44, -3.33, p < 0.001; I2 = 42%, p = 0.14) mm Hg, respectively. CONCLUSIONS: Intravascular RDN using second-generation catheters reduces ambulatory and office BP in patients with essential hypertension. The selection of appropriate hypertensive patients may be the major challenge for the performance of intravascular RDN in routine clinical practice.

Puerarin protects cardiomyocytes from ischemia-reperfusion injury by upregulating LncRNA ANRIL and inhibiting autophagy.

This study analyzed the roles of puerarin and LncRNA ANRIL in myocardial ischemia-reperfusion injury. Hypoxia/reperfusion (H/R) model was established with H9C2 cells. Effects of puerarin of gradient concentrations on cardiomyocytes at different time points of hypoxia and reoxygenation were detected by quantitative real-time polymerase chain reaction (qRT-PCR), cell counting kit-8 (CCK-8), and microscope observation. Effects of puerarin on cardiomyocyte viability, ANRIL expression, contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA), apoptosis, and expressions of autophagy-related genes after H/R injury were determined by CCK-8, quantitative real-time polymerase chain reaction (qRT-PCR), ELISA, flow cytometry, and Western blot, respectively. After cell transfection, the effects of overexpressed and knockdown of ANRIL on cardiomyocytes and H/R-injured cardiomyocytes were examined by rescue experiments. The ischemia-reperfusion (I/R)-injured rat model was established to examine the protective effect of puerarin in vivo. Prolonged hypoxia downregulated ANRIL expression in cardiomyocytes and reduced cardiomyocyte viability. Prolonged reoxygenation increased apoptosis. Both cardiomyocyte viability and ANRIL expression showed a dose-dependent relationship with puerarin. Puerarin reversed the effects of H/R injury on cardiomyocyte viability, ANRIL expression, contents of LDH and MDA, apoptosis, and expressions of autophagy-related genes. Overexpression and knockdown of ANRIL regulated the functions of cardiomyocytes and the expressions of autophagy-related genes. Puerarin reversed the effects of knockdown of ANRIL on H/R-injured cells. The results of In vivo experiments confirmed that puerarin protected myocardial tissues by up-regulating ANRIL and inhibiting autophagy.

Liraglutide reduces systolic blood pressure in patients with type 2 diabetes mellitus: A meta-analysis of randomized trials.

The antidiabetic effect of liraglutide in patients with type 2 diabetes mellitus has been explored in several trials. We performed this meta-analysis determining the effects of liraglutide on blood pressure in these patients. Three electronic databases (Pubmed, Web of Science, and Cochrane Central) were searched for all published articles evaluating the effects of liraglutide on blood pressure in subjects with type 2 diabetes mellitus. Total 968 patients were included in 10 randomized, double-blind, placebo-controlled trials with a follow-up of 16 ± 9 weeks. Liraglutide 1.8 mg/day reduced systolic blood pressure (weighted mean differences -5.39 (95% confidence interval, -7.26, -3.51) mm Hg, p < .001) and body weight (weighted mean differences -2.07 (95% confidence interval, -2.62, -1.51) kg, p < .001) in patients with type 2 diabetes mellitus. There was no significant difference for changes of diastolic blood pressure between liraglutide 1.8 mg/day and placebo in these patients (weighted mean differences -0.53 (95% confidence interval, -1.96, 0.89) mm Hg, p > .05). The increases of heart rate were greater than placebo in patients treated with liraglutide 1.8 mg/day (weighted mean differences 6.03 (95% confidence interval, 4.78, 7.29) kg, p < .001). There was no significant correlation between reduction of systolic blood pressure and weight loss in patients treated with liraglutide 1.8 mg/day (p = .24). In conclusion, liraglutide reduces systolic blood pressure and body weight in patients with type 2 diabetes mellitus. These data suggest the beneficial effects of liraglutide on cardiovascular protection and may improve prognosis in these patients.

Effects of ANRIL polymorphisms on the likelihood of coronary artery disease: A meta-analysis.

BACKGROUND: Whether antisense noncoding RNA in the INK4 locus (ANRIL) polymorphisms are associated with the likelihood of coronary artery disease (CAD) remains controversial. Therefore, we performed this study to explore correlation between ANRIL polymorphisms and CAD. METHODS: Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios and 95% confidence intervals were calculated. RESULTS: Nineteen studies were enrolled for analyses. Pooled overall analyses showed that rs1333040 (dominant model: P < 0.0001; recessive model: P < 0.0001; allele model: P < 0.0001), rs1333049 (dominant model: P = 0.02; allele model: P = 0.02) and rs2383207 (additive model: P = 0.004; allele model: P = 0.03) polymorphisms were significantly associated with the likelihood of CAD. Further subgroup analyses revealed that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms were all significantly correlated with the likelihood of CAD in East Asians. Additionally, rs2383206, rs10757274, and rs10757278 polymorphisms were also significantly correlated with the likelihood of CAD in Caucasians and West Asians. CONCLUSIONS: Our findings indicated that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms may serve as genetic biomarkers of CAD in East Asians. Moreover, rs2383206, rs10757274, and rs10757278 polymorphisms may also serve as genetic biomarkers of CAD in Caucasians and West Asians.

SERP1 prevents hypoxia-reoxygenation-induced H9c2 apoptosis through activating JAK2/STAT3 pathway-dependent attenuation of endoplasmic reticulum stress.

The endoplasmic reticulum (ER) stress plays an important role in myocardial ischemia/reperfusion (MI/R) injury. SERP1, the stress-associated endoplasmic reticulum protein 1, is involved in regulating ER stress response. However, whether it associates with MI/R injury is not identified. Here, we show that SERP1 is induced in the mouse heart after MI/R injury as well as in H9c2 cells under hypoxia/reoxygenation (H/R) treatment. Additionally, SERP1 overexpression reduces H/R-induced H9c2 apoptosis. Moreover, SERP1 overexpression suppresses H/R-induced ER stress and activates JAK2/STAT3 pathway. Furthermore, JAK2/STAT3 pathway inhibition by the specific inhibitor JSI-124 minimizes the suppressive effect of SERP1 overexpression on H/R-induced ER stress and H9c2 apoptosis. Together, these results uncover the protection of SERP1 against H/R-induced H9c2 apoptosis and further relate it to JAK2/STAT3 pathway-dependent attenuation of ER stress. This study suggests SERP1 as a potential regulator invovled in the pathophysiology of MI/R injury.

A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in patients with essential hypertension.

OBJECTIVE: The comparison of antihypertensive effects between telmisartan and candesartan in patients with essential hypertension has been investigated in several small studies. The results were not consistent. We performed this meta-analysis determining the antihypertensive effect of telmisartan versus candesartan in these patients. METHODS: We searched Pubmed, Web of Science, and Cochrane Central for all published studies comparing the antihypertensive effects between telmisartan and candesartan in patients with essential hypertension. RESULTS: The antihypertensive effects were assessed in 302 patients included in 4 trials with a mean follow-up of 10 ± 4 weeks. There were no significant differences between telmisartan and candesartan in reduction of systolic blood pressure (SBP) and diastolic BP (DBP) in patients with essential hypertension (weighted mean differences (WMD) for SBP 1.98 mm Hg (95% confidence interval (CI), -0.53, 4.49), p > 0.05; WMD for DBP 0.26 mm Hg (95% CI, -1.65, 2.16), p > 0.05), respectively. In a sub-analysis including 2 randomized studies, there was not a significant difference for the reduction of SBP (WMD 0.90 (95% CI, -2.88, 4.68) mm Hg, p > 0.05) or DBP (WMD -0.80 (95% CI, -3.40, 1.81) mm Hg, p > 0.05) treated with telmisartan or candesartan. CONCLUSIONS: This meta-analysis provides the evidence that the antihypertensive effects of telmisartan and candesartan are similar on SBP and DBP reduction in patients with essential hypertension, suggesting that strict designed randomized controlled trial would be helpful to compare antihypertensive effects of angiotensin II receptor blockers (ARBs) and improve the choice of ARBs in antihypertensive therapy.

Impact of Physician-Coordinated Intensive Follow-Up on Long-Term Medical Costs in Patients with Unstable Angina Undergoing Percutaneous Coronary Intervention.

BACKGROUND: To investigate the impact of professional physician-coordinated intensive follow-up on long-term expenditures after percutaneous coronary intervention (PCI) in unstable angina (UA) patients. METHODS: In this study, there were 669 UA patients who underwent successful PCI and followed up for 3 years, then divided into the intensive follow-up group (N = 337), and the usual follow-up group (N = 332). Patients were provided with detailed discharge information and individualized follow-up schedules. The intensive group received the extra follow-up times and medical consultations, and all patients were followed up for approximately 3 years. RESULTS: At the 3-year mark after PCI, the cumulative major adverse cardiac events (MACE), recurrence of myocardial ischemia, cardiac death, all-cause death and revascularization in the intensive group were lower than in the usual group. Additionally, the proportion of good medication adherence was significantly higher than in the usual group (56.4% vs. 46.1%, p < 0.001). The hospitalization daytime, total hospitalization cost and total medical cost in the intensive group were lower. Multiple linear regression showed that diabetes, hypertension, intensive follow-up and good medication adherence were associated with emergency and regular clinical cost (p < 0.05), the re-hospitalization cost (p < 0.05) and the total medical cost (p < 0.05) of patient care. Intensive follow-up and good adherence were negatively correlated with the cost of re-hospitalization (standardized coefficients = -0.132, -0.128, p < 0.05) and total medical costs (standardized coefficients = -0.072, -0.086, p < 0.05). CONCLUSIONS: Intensive follow-up can reduce MACE, improve medication adherence and save long-term total medical costs, just by increasing the emergency and regular clinical visits cost in UA patients after PCI.

Furosemide with saline hydration for prevention of contrast-induced nephropathy in patients undergoing coronary angiography: a meta-analysis of randomized controlled trials.

BACKGROUND: The clinical efficacy of furosemide administration in preventing contrast-induced nephropathy (CIN) remains uncertain. This meta-analysis was designed to update data on the incidence of CIN with additional furosemide treatment beyond saline hydration in comparison with hydration alone in patients undergoing percutaneous coronary intervention (PCI). MATERIAL/METHODS: A computerized literature search of MEDLINE, EMBASE, and Cochrane databases was performed. Trials were eligible if they enrolled patients undergoing coronary angiography and randomly allocated participants to receive furosemide administration in addition to saline hydration or saline hydration alone. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for combinations of studies. RESULTS: Five trials involving 1294 patients (640 for additional furosemide treatment and 654 for hydration alone) were included in the meta-analysis. In the synthesis of data, additional furosemide administration had little impact on the incidence of CIN post-PCI compared with peri-procedural saline hydration alone (OR=0.96; 95% CI 0.33-2.84, p=0.95). Moreover, as for the subsequent need for dialysis, there was no statistical significant difference between the 2 groups (OR=1.01; 95% CI 0.38-2.67, p=0.99). Sensitivity analyses did not show any relevant influence on the overall results. There was no publication bias in the meta-analysis. CONCLUSIONS: Furosemide administration did not achieve additional benefit beyond saline hydration in reducing the incidence of CIN in patients undergoing PCI.

Application of Intravascular Ultrasound in the Emergency Diagnosis and Treatment of Patients with ST-Segment Elevation Myocardial Infarction.

PURPOSE: This study aimed to examine the application of intravascular ultrasound (IVUS) in ST-segment elevation myocardial infarction (STEMI) patients with high thrombus burden (thrombus grade ≥3) undergoing emergency diagnosis and primary percutaneous coronary intervention. METHODS: Eighty STEMI patients were enrolled and randomly assigned to the IVUS-guided group (38 patients) or non-IVUS group (42 patients). Stent implantation was performed in non-IVUS group patients. IVUS group patients were further divided into low-risk and high-risk patients on the basis of IVUS evaluation for determining whether stenting should be performed. Major adverse cardiac event (MACE) rates, changes in the left ventricular end-diastolic diameter (LVEDD) and ejection fraction (EF) values, and stent numbers were examined during hospitalization, and follow-up was performed at 1, 3, 6, and 12 months postoperatively. RESULTS: During hospitalization, there were no significant differences in the MACE rates, LVEDD, and EF values and in the follow-up outcomes at 1, 3, 6, and 12 months postoperatively among the patients in the 2 groups (P > 0.05). A significantly lower number of stents were implanted in the IVUS group than in the non-IVUS group patients (P < 0.05). CONCLUSION: During the IVUS-guided emergency intervention, enhanced antithrombotic therapy and best medical care for low-risk STEMI patients may be feasible.

Biodegradable polymer drug-eluting stents versus second-generation drug-eluting stents for patients with coronary artery disease: an update meta-analysis.

OBJECTIVE: Permanent polymer drug-eluting stents (DES) are associated with a higher risk of late and very late stent thrombosis (ST); biodegradable polymer drug-eluting stents (BP-DES) were designed to reduce these risks. However, their benefits are not completely clear. METHOD: We undertook a meta-analysis of randomized studies identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Eligible studies were those that compared BP-DES with second-generation permanent polymer DES in patients undergoing percutaneous coronary intervention. RESULTS: Five studies (8,740 patients) with a mean follow-up of 19.2 months were included. Overall, BP-DES were associated with a broadly equivalent risk of definite and probable ST (odds ratio [OR], 1.07; 95 % confidence interval [CI], 0.67 to 1.71; P = 0.76; I (2) = 5.0 %), target vessel revascularization (OR, 1.04; 95 % CI, 0.87 to 1.24; P = 0.68; I (2) = 38.0 %), all-cause mortality (OR, 1.10; 95 % CI, 0.87 to 1.41; P = 0.42; I (2) = 0.0 %), and major adverse cardiac events (OR, 1.03; 95 % CI, 0.88 to 1.20; P = 0.74; I (2) = 0.0 %) when compared with second-generation DES. However, BP-DES significantly decreased in-stent late luminal loss (standard mean difference [SMD], -0.01; 95 % CI, -0.12 to 0.11; P = 0.93; I (2) = 0.0 %) and in-segment late luminal loss (SMD, -0.06; 95 % CI, -0.17 to 0.05; P = 0.27; I (2) = 0.0 %) compared with second-generation DES. CONCLUSIONS: Compared with second-generation permanent polymer DES, biodegradable stents appear to have equivalent short- to medium-term clinical benefits, and it remains unclear whether they reduce the incidence of very late ST.

Statin therapy decreased the recurrence frequency of atrial fibrillation after electrical cardioversion: a meta-analysis.

BACKGROUND: It is unclear whether statin agents provide clinical benefit in preventing the relapse of atrial fibrillation (AF) after electrical cardioversion (EC). The purpose of this study was to assess the effect of statin agents on the recurrence of AF after EC by conducting a meta-analysis of randomized controlled trials (RCTs). MATERIAL AND METHODS: We conducted a systematic literature search of Medline, EMBASE, ISI Web of Science, and Cochrane databases. RCTs comparing clinical endpoint of the recurrence of AF associated with statin administration vs. no statin treatment (placebo or conventional medical therapy) in patients with AF after EC were eligible. Combined results are presented as risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 5 trials with 524 patients were available for analysis. The pooling analysis showed that statin agents significantly reduced the recurrence of AF after EC compared with no statin treatment (RR=0.76, 95% CI 0.63-0.92; p=0.004; I2=44%). The beneficial effect was shown both in AF subjects receiving atorvastatin or rosuvastatin treatment (atorvastatin 80 mg: RR=0.82, p=0.05; atorvastatin 10 mg: RR=0.27, p=0.03; rosuvastatin: RR=0.38, p=0.04) and in younger patients (<65 years; RR=0.58, p=0.0005). Furthermore, the benefit of statin agents on preventing AF recurrence after EC was demonstrated within 3-month follow-up (p=0.03), and the clinical benefit seemed likely to remain until no less than 12 months after EC (p=0.05). CONCLUSIONS: Based on the currently available data, administration of statin agents, especially atorvastatin or rosuvastatin, is beneficial in lowering the frequency of AF recurrence after EC.

A time-series analysis of short-term ambient ozone exposure and hospitalizations from acute myocardial infarction in Henan, China.

Epidemiological studies in recent years have identified an association between exposure to air pollutants and acute myocardial infarction (AMI); however, the association between short-term ozone (O3) exposure and AMI hospitalization remains unclear, particularly in developing countries. Therefore, this study collected information on 24,489 AMI patients, including daily air pollutant and meteorological data in Henan, China, between 2016 and 2021. A distributed lagged nonlinear model combined with a Poisson regression model was used to estimate the nonlinear lagged effect of O3 on AMI hospitalizations. We also quantified the effects of O3 on the number of AMI hospitalizations, hospitalization days, and hospitalization costs. The results showed that single- and dual-pollution models of O3 at lag0, lag1, and lag (01-07) were risk factors for AMI hospitalizations, with the most significant effect at lag03 (RR = 1.132, 95% CI:1.083-1.182). Further studies showed that males, younger people (15-64 years), warm seasons, and long sunshine duration were more susceptible to O3. Hospitalizations attributable to O3 during the study period accounted for 11.66% of the total hospitalizations, corresponding to 2856 patients, 33,492 hospital days, and 90 million RMB. Maintaining O3 at 10-130 µg/m3 can prevent hundreds of AMI hospitalizations and save millions of RMB per year in Henan, China. In conclusion, we found that short-term exposure to O3 was significantly associated with an increased risk of hospitalization for AMI in Henan, China, and that further reductions in ambient O3 levels may have substantial health and economic benefits for patients and local healthcare facilities.

[Effects of docosahexaenoic acid on ion channels of rat coronary artery smooth muscle cells].

OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels and voltage-dependent K(+) (K(V)) channels in rat coronary artery smooth muscle cells (CASMCs), and evaluate the vasorelaxation mechanisms of DHA. METHODS: BK(Ca) and K(V) currents in individual CASMC were recorded by patch-clamp technique in whole-cell configuration. Effects of DHA at various concentrations (0, 10, 20, 40, 60 and 80 µmol/L) on BK(Ca) and K(V) channels were observed. RESULTS: (1) DHA enhanced IBK(Ca) and BK(Ca) tail currents in a concentration-dependent manner while did not affect the stably activated curves of IBK(Ca). IBK(Ca) current densities were (68.2 ± 22.8), (72.4 ± 24.5), (120.4 ± 37.9), (237.5 ± 53.2), (323.6 ± 74.8) and (370.6 ± 88.2)pA/pF respectively (P < 0.05, n = 30) with the addition of 0, 10, 20, 40, 60 and 80 µmol/L DHA concentration, and half-effect concentration (EC(50)) of DHA was (36.22 ± 2.17)µmol/L. (2) IK(V) and K(V) tail currents were gradually reduced, stably activated curves of IK(V) were shift to the right, and stably inactivated curves were shifted to the left in the presence of DHA. IK(V) current densities were (43.9 ± 2.3), (43.8 ± 2.3), (42.9 ± 2.0), (32.3 ± 1.9), (11.7 ± 1.5) and (9.6 ± 1.2)pA/pF respectively(P < 0.05, n = 30)post treatment with 0, 10, 20, 40, 60 and 80 µmol/L DHA under manding potential equal to +50 mV, and EC(50) of DHA was (44.19 ± 0.63)µmol/L. CONCLUSION: DHA can activate BK(Ca) channels and block K(V) channels in rat CASMCs, the combined effects on BK(Ca) and K(V) channels lead to the vasodilation effects of DHA on vascular smooth muscle cells.

[Effects of docosahexaenoic acid on sodium channel current and transient outward potassium channel current in rat ventricular myocytes].

OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) on sodium channel current (I(Na)) and transient outward potassium channel current (I(to)) in rat ventricular myocytes and to evaluate potential anti-arrhythmic mechanisms of DHA. METHODS: I(Na) and I(to) of individual ventricular myocytes were recorded by patch-clamp technique in whole-cell configuration at room temperature. Effects of DHA at various concentrations (0, 20, 40, 60, 80, 100 and 120 micromol/L) on I(Na) and I(to) were observed. RESULTS: (1) I(Na) was blocked in a concentration-dependent manner by DHA, stably inactivated curves were shifted to the left, and recover time from inactivation was prolonged while stably activated curves were not affected by DHA. At -30 mV, I(Na) was blocked to (1.51 ± 1.32)%, (21.13 ± 4.62)%, (51.61 ± 5.73)%, (67.62 ± 6.52)%, (73.49 ± 7.59)% and (79.95 ± 7.62)% in the presence of above DHA concentrations (all P < 0.05, n = 20), and half-effect concentration (EC(50)) of DHA on I(Na) was (47.91 ± 1.57)micromol/L. (2) I(to) were also blocked in a concentration-dependent manner by DHA, stably inactivated curves were shifted to the left, and recover time from inactivation was prolonged with increasing concentrations of DHA, and stably activated curves were not affected by DHA. At +70 mV, I(to) was blocked to (2.61 ± 0.26)%, (21.79 ± 4.85)%, (63.11 ± 6.57)%, (75.52 ± 7.26)%, (81.82 ± 7.63)% and (84.33 ± 8.25)%, respectively, in the presence of above DHA concentrations (all P < 0.05, n = 20), and the EC(50) of DHA on I(to) was (49.11 ± 2.68)micromol/L. CONCLUSION: The blocking effects of DHA on APD and I(to) may serve as one of the anti-arrhythmia mechanisms of DHA.

Yixintongmai Inhibits Proliferation and Migration and Promotes Apoptosis of Vascular Smooth Muscle Cells Cultured with High Glucose.

OBJECTIVE: This study was designed to evaluate the effects of yixintongmai on proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) cultured with high glucose. METHODS: VSMCs of the thoracic aorta from 5- to 8-week-old male Sprague-Dawley rats were cultured with normal (4.5 mM) or high (25 mM) glucose, respectively. The concentration of yixintongmai powder at 360 µg/ml was chosen according to pre-experimental results. RESULTS: Yixintongmai inhibited the proliferation of VSMCs (CCK-8 assay: 0.75 ± 0.04 versus 0.98 ± 0.09 OD, P < 0.001; cell counting: 37533 ± 1861 versus 56009 ± 3779 cells/well, P < 0.001) and the expression of proliferating cell nuclear antigen (0.74 ± 0.08 fold, P < 0.001) as compared with high glucose (HG). Yixintongmai inhibited the migration of VSMCs (transwell assay: 146 ± 16 versus 265 ± 62 cells; P < 0.001), scratch wound assay (0.17 ± 0.01 fold, P < 0.001), and the expression of matrix metalloproteinases-9 (0.87 ± 0.03 fold, P < 0.001) as compared with HG. Yixintongmai decreased mitochondrial membrane potentials (0.36 ± 0.12 fold, P < 0.001) and promoted early (2.11 ± 0.20 fold, P < 0.01) and late (2.11 ± 0.28 fold, P < 0.01) apoptosis of VSMCs as compared with HG. Yixintongmai inhibited the expression of B-cell lymphoma 2 (0.83 ± 0.07 fold, P < 0.01) and stimulated the activity of cleaved-capase-3/caspase-3 (2.00 ± 0.12 fold, P < 0.05) as compared with HG. Yixintongmai inhibited reactive oxygen species generation (0.46 ± 0.03 fold, P < 0.01) and the expression of NADPH oxidase-1 (0.84 ± 0.04 fold, P < 0.001), nuclear factor-kappa B (NF-κB) p65 (0.71 ± 0.07 fold, P < 0.001), phosphorylated NF-κB p65 (0.39 ± 0.02 fold, P < 0.0001), and inhibited nuclear translocation of NF-κB p65 (0.87 ± 0.03 fold, P < 0.001) in VSMCs as compared with HG. CONCLUSIONS: Yixintongmai inhibits the proliferation and migration and promotes the apoptosis of VSMCs cultured with HG, which suggests the potential anti-atherosclerotic effects of this traditional Chinese medicine.

Chronotherapy of Hypertension with Angiotensin Receptor Blockers-A Meta-Analysis of Blood Pressure Measured by Ambulatory Blood Pressure Monitoring in Randomized Trials.

BACKGROUND: We performed this meta-analysis evaluating the efficacy of chronotherapy of hypertension with angiotensin receptor blockers (ARBs). METHODS: We searched Pubmed, Web of Science, and Cochrane for all published randomized trials that compare antihypertensive effects of ARBs between bedtime dosing and awakening dosing. Blood pressure (BP) was measured by ambulatory BP monitoring in patients with mild or moderate essential hypertension. RESULTS: The effects of ARBs on BP were assessed in 805 essential hypertensive patients included in 8 trials with a follow-up of 12 ± 3 weeks. The sleep-time systolic and diastolic BP (SBP, DBP) with bedtime dosing greatly decreased as compared with awakening dosing (weighted mean differences [WMD] for SBP WMD -5.23 [95% confidence intervals (CI), -7.27, -3.20] mm Hg, p < 0.001; WMD for DBP -2.94 [95% CI, -4.52, -1.36] mm Hg, p < 0.001). The reduction of daytime SBP (WMD 0.98 [95% CI, -0.20, 2.17] mm Hg, p = 0.10), DBP (WMD 0.11 [95% CI, -0.68, 0.89] mm Hg, p = 0.79), 24 hour SBP (WMD -0.75 [95% CI, -1.93, 0.42] mm Hg, p = 0.21) and DBP (WMD -0. 77 [95% CI, -1.55 0.01] mm Hg, p = 0.05) with bedtime dosing was similar with awakening dosing. CONCLUSIONS: Bedtime dosing with ARBs is more effective in lowering sleep-time BP than awakening dosing in patients with essential hypertension, suggesting a utilization of chronotherapy of hypertension with ARBs to reduce sleep-time high BP. Larger multi-ethnic studies are needed to investigate the efficacy of chronotherapy of hypertension.

Long-term changes in ischemic burden after chronic total occlusion percutaneous coronary intervention: a retrospective observational study.

OBJECTIVE: There is uncertainty of the benefit of percutaneous coronary intervention (PCI) for chronic coronary total occlusion (CTO). The study aimed to investigate potential long-term changes in ischemic burden in patients with CTO after PCI. METHODS: Patients who underwent CTO PCI with available records of 15O-H2O positron emission tomography within 3 months prior to and at least 6 months after successful CTO PCI were retrospectively included. Data on perfusion defect size, hyperemic myocardial blood flow (MBF), and coronary flow reserve (CFR) within the CTO area before and after CTO PCI were extracted and compared for evaluating ischemic burden. The comparisons were also performed after stratifying by baseline perfusion defect sizes. RESULTS: A total of 74 eligible patients were included with an average age of 62.0±7.5 years. Significant decrease in perfusion defect size (3 (2-4) versus 1 (0-2) segments, P<0.001) and significant increase in hyperemic MBF (1.32±0.39 versus 2.27±0.52 mL/min/g, P<0.001) and CFR (1.72±0.47 versus 2.73±0.73, P<0.001) were observed after CTO PCI when compared to that at baseline. When stratifying by baseline perfusion defect size, no significant differences were observed between groups in changes of hyperemic MBF (P=0.301) and CFR (P=0.850), but patients with larger perfusion defect size exhibited greater reduction in perfusion defect size (P<0.001). CONCLUSIONS: CTO PCI relieved ischemic burden for at least 6 months, and patients with larger baseline perfusion defect size might benefit more from CTO PCI in terms of ischemic burden.

[Echocardiographic standardized myocardial segmentation features in patients with left ventricular noncompaction].

OBJECTIVE: To analyze the echocardiographic standardized myocardial segmentation features in patients with left ventricular noncompaction (LVNC). METHODS: Echocardiographic characteristics of 9 patients with LVNC were analyzed and the localization of lesions were determined according to the standardized myocardial segmentation (SMS) recommended by American Heart Association (AHA). RESULTS: Loose trabeculation in the myocardial lesions were evidenced in all LVNC patients. Communication between deep intertrabecular recess and LV cavity was evident with color flow imaging. According to SMS of AHA, noncompaction of ventricular myocardium was localized in apical segment in all 9 patients, in apical segment of the inferior wall (IW) in 9 patients, in apical segment of the lateral wall (LW) in 7 patients, in middle segment (MS) of IW in 7 patients, in MS of LW in 6 patients. One NC segment was also evidenced in apical segment and MS of septal ventricular wall, basal segment of IW and LW and right ventricular apex, respectively. NC was not found in left ventricular anterior wall. CONCLUSION: Echocardiographic standardized myocardial segmentation is helpful to diagnose LVNC and NC was mostly localized in the apical segments of LVNC patients.

Fluorescent Magnetic Iron Oxide NanoparticleEncapsulated Protein Hydrogel Against Doxorubicin-Associated Cardiotoxicity and for Enhanced Cardiomyocyte Survival.

Doxorubicin (DOX) is a widely used and effective anticancer drug. However, it shows high cardiotoxicity in several patients. The exact biological mechanisms of DOX-induced cardiotoxicity remain unclear. In the present study, we developed and assessed novel injectable hydrogel matrices combined with nanoparticles and secretome biomolecules to reduce DOXinduced cytotoxicity in human stem cell-derived cardiomyocytes. A Fe2O3 nanoparticle-loaded biocompatible silk sericin nanocomposite form was fabricated and used as an injectable carrier for secretome for in vivo cardiomyocyte metabolism. The formulated hydrogels carrying secretome were analyzed in vitro for proliferation, migration, and tube formation of human stem cell-derived cardiomyocytes. Biological analyses revealed that the secretome-encapsulated florescent Fe3O2 Silk sericin (Sec@MSS) hydrogel markedly reduced calcein-PI dual staining in cardiomyocytes, revealing significantly induced apoptosis. Furthermore, we evaluated the mitochondrial membrane potential for DOX and Sec@MSS hydrogel, and demonstrated apoptosis of the cardiomyocytes in the DOX-alone and Sec@MSS groups. However, the cardiotoxicity of Sec@MSS sericin was much lower than that in the DOX group, and was further evaluated via VEGFR and TUNEL analyses. The results indicate that Sec@MSS hydrogel might serve as an effective treatment agent in cardiac diseases in the future.