Cardioprotection of ischemic preconditioning in rats involves upregulating adiponectin.

It has been reported that ischemic preconditioning (IPC) and adiponectin (APN) are cardioprotective in many cardiovascular disorders. However, whether APN mediates the effect of IPC on myocardial injury has not been elucidated. This study was conducted to investigate whether IPC affects myocardial ischemic injury by increasing APN expression. Male adult rats with cardiac knockdowns of APN and its receptors via intramyocardial small-interfering RNA injection were subjected to IPC and then myocardial infarction (MI) at 24 h after IPC. Globular APN (gAd) was injected at 10 min before MI. APN mRNA and protein levels in myocardium as well as the plasma APN concentration were markedly high at 6 and 12 h after IPC. IPC ameliorated myocardial injury as evidenced by improved cardiac functions and a reduced infarct size. Compared with the control MI group, rats in the IPC + MI group had elevated levels of left ventricular ejection fraction and fractional shortening and a smaller MI size (P < 0.05). However, the aforementioned protective effects were ameliorated in the absence of APN and APN receptors, followed by the inhibition of AMP-activated protein kinase (AMPK) phosphorylation, but reversed by gAd treatment in wild-type rats, and AMPK phosphorylation increased (P < 0.05). Overall, our results suggest that the cardioprotective effects of IPC are partially due to upregulation of APN and provide a further insight into IPC-mediated signaling effects.

Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction.

BACKGROUND/AIMS: High ADAMTS-7 levels are associated with acute myocardial infarction (AMI), although its involvement in ventricular remodeling is unclear. In this study, we investigated the association between ADAMTS-7 expression and cardiac function in a rat AMI model. METHODS: Sprague-Dawley rats were randomized into AMI (n = 40) and sham (n = 20) groups. The left anterior descending artery was sutured to model AMI. Before surgery and 7, 14, 28, and 42 days post-surgery, ADAMTS-7 and brain natriuretic peptide (BNP), and cartilage oligomeric matrix protein (COMP) were assessed by ELISA, western blot, real-time RT-PCR, and/or immunohistochemistry. Cardiac functional and structural parameters were assessed by M-mode echocardiography. RESULTS: After AMI, plasma ADAMTS-7 levels increased, peaking on day 28 (AMI: 13.2 ± 6.3 vs. sham: 3.4 ± 1.3 ng/ml, P < 0.05). Compared with the sham group, ADAMTS-7 expression was higher in the infarct zone at day 28. COMP present in normal myocardium was degraded by day 28 post-AMI. Plasma ADAMTS-7 correlated positively with BNP (r = 0.642, P = 0.025), left ventricular end-diastolic diameter (r = 0.695, P = 0.041), left ventricular end-systolic diameter (r = 0.710, P = 0.039), left ventricular ejection fraction (r = 0.695, P = 0.036), and left ventricular short-axis fractional shortening (r = 0.721, P = 0.024). CONCLUSIONS: ADAMTS-7 levels may reflect the degree of ventricular remodeling after AMI.

Association between plasma ADAMTS-7 levels and ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: The metalloproteinase family of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) degrades extracellular matrix. However, the relevance of the ADAMTS family to cardiovascular diseases remains largely unknown. The study aimed to examine plasma ADAMTS-7 levels in patients with acute myocardial infarction (AMI) and the relationship between plasma ADAMTS-7 levels and heart function. METHODS: This was a prospective study performed in 84 patients with ST-elevation myocardial infarction (STEMI), 70 patients with non-STEMI (NSTEMI), and 38 controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma ADAMTS-7 levels. Cardiac structure and function were assessed using two-dimensional transthoracic echocardiography. Patients were stratified according to left ventricular ejection fraction (LVEF) ≤ 35% or >35%. RESULTS: Plasma ADAMTS-7 levels were higher in patients with LVEF ≤ 35% compared with those with LVEF >35% (6.73 ± 2.47 vs. 3.22 ± 2.05 ng/ml, P < 0.05). Plasma ADAMTS-7 levels were positively correlated with brain natriuretic peptide (BNP), left ventricular mass index (LVMI), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD) and negatively correlated with the 6-min walk test (P < 0.05). According to the receiver operating characteristic (ROC) curve, using a cutoff value of plasma ADAMTS-7 of 5.69 ng/ml was associated with a specificity of 61.0% and a sensitivity of 87.6% for the diagnosis of heart failure after AMI. Logistic regression analysis indicated that the association between ADAMTS-7 and heart failure after AMI was independent from traditional cardiovascular risk factors and other biomarkers (odds ratio = 1.236, 95% confidence interval: 1.023 to 1.378, P = 0.021). CONCLUSIONS: Elevated ADAMTS-7 level may be involved in ventricular remodeling after AMI.

Ambulatory arterial stiffness index correlates with ambulatory pulse pressure but not dipping status in patients with grade 1/grade 2 essential hypertension.

OBJECTIVE: To evaluate the relationship between ambulatory arterial stiffness index (AASI) and other parameters derived from ambulatory blood pressure (BP) monitoring, including dipping status, in patients with grade 1/grade 2 hypertension. METHODS: This retrospective analysis included baseline data from Chinese outpatients enrolled into a previous study, who had clinic diastolic BP of 90-109 mmHg and systolic BP <180 mmHg, had undergone 24-h ambulatory BP monitoring and routine blood chemistry investigations, and had estimated glomerular filtration rate (eGFR) data. RESULTS: Out of 120 patients screened, 87 were included. No significant difference in 24-h AASI was found between dippers and nondippers. The 24-h AASI significantly correlated with age, systolic BP and pulse pressure, and inversely correlated with 24-h diastolic BP variation and eGFR. In dippers and nondippers, AASI correlated with daytime pulse pressure, daytime diastolic BP variation and eGFR; in nondippers, AASI also correlated with 24-h systolic BP and 24-h pulse pressure. The 24-h AASI was significantly associated with 24-h pulse pressure and daytime pulse pressure. CONCLUSION: In patients with grade 1/grade 2 essential hypertension, AASI shows a significant correlation with ambulatory pulse pressure.

The preventive effect of garlicin on a porcine model of myocardial infarction reperfusion no-reflow.

OBJECTIVE: To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). METHODS: Twenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA). RESULTS: Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01). CONCLUSIONS: Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

[The effects of olmesartan on ambulatory blood pressures and blood pressure variability in patients with mild to moderate essential hypertension].

OBJECTIVE: To evaluate the effect of olmesartan medoxomil tablets (olmesartan) in comparison with Olmetec on 24 h ambulatory blood pressure (ABPM) and blood pressure variability (BPV) in patients with mild to moderate hypertension. METHODS: A randomized, double-blind, double-mimic controlled trial was performed.Forty-eight patients with mild to moderate essential hypertension were randomly into treatment group (olmesartan) and control group (Olmetec) for eight weeks. The ABPM was taken before and at the end of the trial. RESULTS: After eight weeks, treatment with olmesartan induced a significant reduction in ABPM in patients [(9 ± 3)/(11 ± 3) mmHg(1 mmHg = 0.133 kPa)], which is similar with the reduction by Olmetec [(9 ± 4)/(9 ± 5) mmHg], P > 0.05. This situation holds for BPV with the standard deviations of 24 h, systolic blood pressure/diastolic blood pressure of pre-treatment and pro-treatment were (10 ± 2)/(11 ± 3) mmHg vs (10 ± 3)/(12 ± 2) mmHg in olmesartan group, and (10 ± 3)/(11 ± 3) mmHg vs (12 ± 3)/(12 ± 4) mmHg in Olmetec group. (3) There is no difference in the rate of adverse event between olmesartan (10.42%) and Olmetec (8.33%) treatment (P > 0.05). CONCLUSION: Similar to Olmetec, treatment with olmesartan once daily can significantly reduce ABPM in patients with mild to moderate essential hypertension.

[The effects of aranidipine on ambulatory blood pressures in patients with mild to moderate essential hypertension].

OBJECTIVE: To evaluate the effect of aranidipine enteric-coated capsules on 24 h blood pressure and blood pressure variability (BPV) in patients with mild to moderate essential hypertension. METHODS: This was an open clinical trial with 2 weeks of placebo run-in period. A total of 74 patients with blood pressure (140-180/95-110 mm Hg (1 mm Hg = 0.133 kPa) were treated by aranidipine (5 mg/d) for 4 weeks.If clinical sitting blood pressure < 140/90 mm Hg at 4th week, aranidipine at 5 mg/d would be continued for another 8 weeks.If not, the dosage would be increased to 10 mg/d.If blood pressure <140/90 mm Hg at 8th week, aranidipine at 5 mg/d or 10 mg/d would be given constantly.If not, the dosage would be increased to 20 mg/d and given for another 4 weeks. All patients performed 24 h ambulatory blood pressure monitoring (ABPM) before and after the treatment with BPV evaluated by the average 24 h per unit time blood pressure standard deviation and morning blood pressure surge (MBPS). RESULTS: (1) After 12 weeks' treatment with aranidipine, the mean 24 h blood pressure was reduced significantly compared with the baseline [(14 ± 13)/(11 ± 9) mm Hg, both P < 0.05] with trough/peak (T/P) ratio of SBP and DBP in responders of 75.31% and 78.15%, respectively.(2) After 12 weeks' treatment, standard deviations of 24 h, daytime SBP/DBP and nighttime SBP/DBP were reduced significantly[(25 ± 3)/(14 ± 4) mm Hg vs (11 ± 3)/(8 ± 2) mm Hg, (24 ± 5)/(14 ± 4) mm Hg vs (11 ± 3)/(8 ± 2) mm Hg, (10 ± 3)/(8 ± 4) mm Hg vs (8 ± 3)/(6 ± 3) mm Hg], respectively with all P < 0.05.Significant decrease was shown in MBPS compared to the baseline [(27 ± 11) mm Hg vs (19 ± 9) mm Hg, P < 0.05]. (3) The incidence of adverse events was 13.4%, including mild dizziness, flushing and palpitation. CONCLUSION: Administration of aranidipine enteric-coated capsules can control 24 h blood pressure effectively and reduce BPV significantly in patients with mild to moderate essential hypertension with good safety profile.

[Association between left ventricular diastolic function and blood pressure variability in essential hypertensive patients].

OBJECTIVE: To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension. METHODS: Left ventricular diastolic function of 252 hypertensive patients were assessed by early (E) diastolic transmitral flows to early diastolic mitral annular velocity (Ea) (E/Ea) ratio derived from Doppler echocardiography. Patients were divided into two groups according to normal left ventricular diastolic function group (E/Ea<15, n = 168) and left ventricular diastolic dysfunction group (E/Ea ≥ 15, n = 84). All patients were monitored by ambulatory blood pressure. Standard deviation (SD) and coefficient of variation (CV) of blood pressure were calculated as the BPV. Relationship between BPV and left ventricular diastolic function were analyzed by multivariate logistic regression analysis. RESULTS: All-day average diastolic blood pressure(DBP), the day systolic blood pressure (SBP), night SBP, night DBP, SBPSD, DBPSD and DBPCV in the left ventricular diastolic dysfunction group were significantly higher than in the normal diastolic function group (all P < 0.05). Multivariate logistic regression analysis showed that left ventricular diastolic dysfunction was associated with SBPSD (OR:1.126, 95%CI:1.054-1.203, P < 0.01), SBPCV (OR:1.127, 95%CI:1.036-1.225, P < 0.01) in this patient cohort. CONCLUSION: High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients.

[Efficacy and safety of aranidipine in Chinese patients with mild-to-moderate essential hypertension].

OBJECTIVE: To assess the efficacy and safety of aranidipine versus retard-released felodipine in Chinese patients with mild-to-moderate essential hypertension. METHODS: This was a multicenter, randomized, double-blind, placebo and active antihypertensive drug parallel-controlled study. After 2 weeks of placebo run-in period, 315 patients at 6 centers with diastolic blood pressure (DBP) between 95 to 109 mm Hg (1 mm Hg = 0.133 kPa) while systolic blood pressure (SBP) below 180 mm Hg were randomized to receive aranidipine 5-20 mg/d (n = 126) or retard-released felodipine 5-10 mg/d (n = 126) for 12 weeks. Others (n = 63) received placebo for 4 weeks. Their blood pressures were evaluated at baseline and the end of Weeks 4, 8 and 12. RESULTS: After a 12-week treatment, SBP decreased from 148.8 ± 10.7 mm Hg to (132.8 ± 11.2) mm Hg while DBP dropped from ( 98.4 ± 2.8) mm Hg to (83.9 ± 7.5) mm Hg. There were significant differences with the baseline values (P < 0.0001). After a 4-week treatment, the reductions of SBP in aranidipine and retard-released felodipine groups were (12.1 ± 11.0) mm Hg and (12.2 ± 11.2) mm Hg while the reductions of DBP in two groups (11.8 ± 6.9) mm Hg and (12.1 ± 7.9) mm Hg respectively. The reductions of SBP and DBP in two groups were (2.3 ± 8.4) mm Hg and (4.0 ± 5.1) mm Hg and they were significantly superior to that in placebo group (P < 0.0001). But no significant difference existed between aranidipine and retard-released felodipine groups. Also no significant differences were found between these two antihypertensive therapy groups at the end of Weeks 4, 8 and 12 in the reduction of blood pressure, total response rate and blood pressure control rate. But 20 mg daily aranidipine was significantly superior to 10 mg daily retard-released felodipine in the control rates of SBP and DBP. Adverse events occurred at 24.22% and 29.92% in aranidipine and retard-released felodipine groups respectively (P = 0.305). CONCLUSION: Administration of aranidipine 5-20 mg/d can effectively control blood pressure and is not inferior to retard-released felodipine 5-10 mg/d. The efficacy of 20 mg/d aranidipine is superior to that of retard-released felodipine 5-10 mg/d. And the effectiveness and safety of aranidipine are similar to those of retard-released felodipine.