Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway.

Schizandrin B exhibits prominent antioxidant and anti-inflammatory effects, and plays an important role in ameliorating myocardial ischemia/reperfusion injury. However, the underlying protective mechanisms remain to be elucidated. The aim of the present study was to explore the cardioprotective effects of schizandrin B against hypoxia/reoxygenation (H/R)-induced H9c2 cell injury, focusing on the role of the adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this process. The results showed that schizandrin B attenuated the H/R-induced decrease in cell viability and the increase in lactate dehydrogenase release, as well as the apoptosis rate in H9c2 cells. Schizandrin B also mitigated H/R-induced oxidative stress, as illustrated by the decrease in intracellular reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in antioxidant enzyme superoxide dismutase and glutathione peroxidase activities. In addition, schizandrin B reversed the H/R-induced upregulation of pro-inflammatory cytokines [interleukin (IL)-1ß (IL-1ß) tumor necrosis factor-α, IL-6 and IL-8] and the downregulation of anti-inflammatory cytokines (transforming growth factor-ß and IL-10) in the culture supernatant. Notably, schizandrin B increased the expression of Nrf2, NAD(P)H: Quinone oxidoreductase (NQO-1) and heme oxygenase-1 (HO-1) in H/R-treated H9c2 cells, activating the Nrf2 signaling pathway. The cardioprotection of schizandrin B against H/R injury was inhibited by Nrf2 knockdown induced byNrf-2-specific small interfering RNA (siRNA; si-Nrf2) transfection. Furthermore, schizandrin B enhanced phosphorylated (p)-AMPK expression, while AMPK knockdown induced by AMPK-specific siRNA(si-AMPK) transfection remarkably eliminated schizandrin B-induced cardioprotection and reduced Nrf2 expression in H/R-treated H9c2 cells. Taken together, these results suggested that schizandrin B exerts cardioprotection on H/R injury in H9c2 cells due to its antioxidant and anti-inflammatory activities via activation of the AMPK/Nrf2 pathway.

Pitavastatin Combined with Ezetimibe Treatment was an Effective Approach to Non-IRA Lesion of ST-segment Elevation Myocardial Infarction Patients with Primary Percutaneous Coronary Intervention.

OBJECTIVE: ST-Segment Elevation Myocardial Infarction (STEMI) patients with the multivessel disease have distinctive plaque characteristics in non-IRA lesions. Intensive statin therapy was a potential approach to treat STEMI patients with the non-IRA disease. However, there is still poor evidence about the therapeutic effect. In this study, we have evaluated the detailed therapeutic effect of statin plus ezetimibe intensive therapy. METHODS: For STEMI patients with non-IRA disease undergoing primary Percutaneous Coronary Intervention (PCI), 183 control STEMI patients without non-IRA disease undergoing primary PCI, and 200 STEMI patients with non-IRA disease undergoing primary PCI were introduced into this study. 200 STEMI patients with non-IRA disease undergoing primary PCI were divided into Normal group, Intensive group, Normal & Combined group, and Intensive & Combined group. The baseline information for each participant was recorded. Meanwhile, the physiological and biochemical indicators of each member with different treatments were collected after one-year follow-up. RESULTS: For STEMI patients with non-IRA disease undergoing primary PCI, no differences could be detected in multiple indexes such as OCT examination results, age, stroke, etc. However, diabetes mellitus, smoking, and coronary Gensini score were different between different groups (P<0.05). After one year follow-up, cholesterol, low-density lipoprotein, coronary Gensini score, thin-cap fibroatheroma, length of non-infarcted arterial lesions, non-infarct artery lesion range, myocardial infarction again, and revascularization again were significantly different between different groups (P<0.05). CONCLUSION: The results mentioned above suggested that pitavastatin combined with ezetimibe was an effective approach for STEMI patients with non-IRA disease undergoing primary PCI. The results obtained in this study have provided a novel method for the treatment of STEMI patients with non-IRA disease undergoing primary PCI.

[High-dose tirofiban in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention].

OBJECTIVE: To evaluate the clinical outcomes of high-dose tirofiban in patients with ST-elevation myocardial infarction (ASTEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 104 consecutive ASTEMI patients undergoing primary PCI were enrolled from January 2010 to February 2011. They were randomized into the high-dose tirofiban group (n = 52) and the normal-dose tirofiban group (n = 52). We measured the sumST-segment resolution of ECG post-PCI respectively and left ventricular ejective fraction (LVEF) at Day 90 post-PCI. RESULTS: After PCI, the sumST-segment resolution of ECG of the high-dose tirofiban group significantly improved than that of the normal-dose tirofiban group (38% ± 12% vs 34% ± 13%, P < 0.05). Before PCI, LVEF of two groups is 50.2% ± 1.4% vs 49.6% ± 1.1% (P > 0.05), but at day 90 post-PCI, LVEF had significant difference between two groups (60.1% ± 1.1% vs 56.0% ± 1.2%, P < 0.05). The rates of major and moderate hemorrhage did not differ significantly between two groups. CONCLUSION: High-dose tirofiban improves myocardial reperfusion and clinical outcome. It re-emphasizes the importance of further platelet aggregation inhibition in ASTEMI patients undergoing primary PCI.

[High maintenance dose of clopidogrel improves long-term clinical outcomes in patients with elective percutaneous coronary intervention].

OBJECTIVE: To evaluate the efficacy of a 300 mg loading dose of clopidogrel followed by 150 mg as maintenance dose in patients with percutaneous coronary intervention (PCI). METHODS: A total of 108 consecutive patients undergoing elective PCI were recruited from our hospital from July 2007 to July 2008. A 300 mg loading dose was administered prior to PCI. Then they were randomized to receive clopidogrel 75 mg (n = 55) or 150 mg (n = 46) daily for 30 days. From Day 30 to Month 6 post-operation, all of them received 75 mg/d clopidogrel and were followed up for a mean period of 6 months. RESULTS: Thirty days after PCI, the platelet inhibition of the 150 mg group was significantly higher than the 75 mg group (64.2% ± 13.3% vs 52.6% ± 14.3%, P = 0.00). The ratios of fatal or non-fatal myocardial infarction (MI) (1(1.8%) vs 3 (6.5%), P = 0.405) and target vessel revascularization (TVR) (4(7.2%) vs 6 (13.0%), P = 0.714) were significantly lower in the 150 mg group than those in the 75 mg group. So the overall incidence of MACE including death, MI and TVR was obviously lower in the 150 mg group than that in the 75 mg group (13.0% vs 20.2%, absolute risk reduction 7.3%). CONCLUSION: A high clopidogrel maintenance dose of 150 mg daily for the first month after PCI reduces the risk of long-term adverse events in patients with elective percutaneous coronary intervention.

[Prognostic significance of admission N-terminal pro-brain natriuretic peptide in predicting angiographic no-reflow phenomenon during percutaneous coronary intervention in patients with acute myocardial infarction].

OBJECTIVE: To determine the relationship between N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and angiographic no-reflow phenomenon in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI). METHODS: The data of 106 consecutive AMI patients undergoing primary PCl were collected and analyzed retrospectively. NT-proBNP was obtained pre-PCI at admission. According to the NT-proBNP level, they were divided into normal and elevated NT-proBNP groups. The no-reflow phenomenon was defined as an angiographic outcome of Thrombolysis In Myocardial Infarction (TIMI) grade < 3 without accompanying mechanical factors. RESULTS: The patients with elevated NT-proBNP on admission had a higher incidence of no-reflow phenomenon than those with NT-proBNP level. Compared to normal reflow counterparts, no-reflow patients had a higher NT-proBNP level [1883 ng/L (484 ∼ 5500 ng/L) vs 220 ng/L (87 ∼ 926 ng/L) P = 0.046]. Multivariate analysis showed that a high NT-proBNP level (NT-proBNP > 1765 ng/L) on admission was an independent predictor of no-reflow. This cut-off value yielded a sensitivity of 60.0% and a specificity of 87.5% respectively. CONCLUSION: The NT-proBNP level on admission may be a prognostic biomarker in the prediction of the development of angiographic "no-reflow" phenomenon after primary PCI for AMI patients.

[Effect of tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention].

OBJECTIVE: To observe the effect of glycoprotein receptor blockade tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention (PCI). METHODS: From April 2006 to April 2008, 157 acute anterior myocardial infarction patients without ST segment resolution after PCI were randomly allocated to tirofiban (intravenous bolus 10 microg/kg followed by intravenous infusion of 0.15 microgxkg(-1)xmin(-1) for 48 h, n = 80) or equal volume saline (control group, n = 77). Baseline characteristics, PCI features and clinical outcomes during hospitalization, left ventricular ejection fractions (LVEF) and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at 30 and 180 days after discharge were compared between the two groups. RESULTS: The baseline clinical characteristics were comparable between the two groups. Compared to control group, the MACE rates and re-infarction rates at 30 days (6.3% vs.18.2%, P < 0.05; 1.3% vs.9.1%, P < 0.05, respectively) and 180 days (10.0% vs.23.4%, P < 0.05; 2.5% vs.10.4%, P < 0.05, respectively) were significantly reduced in tirofiban group. LVEF value was significantly higher in tirofiban group at 30 days and 180 days compared with those in control group [(51 +/- 6)% vs. (46 +/- 8)%, P < 0.05; (57 +/- 7)% vs. (50 +/- 9)%, P < 0.05]. Hemorrhagic complications were similar between the two groups. CONCLUSION: Use of tirofiban for acute anterior myocardial infarction patients without ST segment resolution after PCI is safe and can significantly improve 30 and 180 days clinical outcomes after discharge.

[Clinical outcomes of trimetazidine in patients with acute ST segment elevation myocardial infarction without ST segment resolution after primary percutaneous coronary intervention].

OBJECTIVE: To evaluate prospectively the clinical outcomes of trimetazidine (TMZ) in patients with acute ST segment elevation myocardial infarction (STEMI) without ST segment resolution (STR) after primary percutaneous coronary intervention (PPCI). METHODS: From August 2005 to October 2007, 138 acute STEMI patients without STR after PPCI were randomly assigned to either with TMZ therapy (TMZ group, n = 70) or without TMZ (control group, n = 68). Baseline characteristics, PCI features and clinical outcomes during hospitalization were compared between the two groups. Left ventricular ejection fraction (LVEF) and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at Days 30 and 180 after discharge were also compared. RESULTS: The baseline clinical characteristics were comparable between the two groups. There was no significant difference in MACE rates at Days 30 and 180 between the two groups (10/70 vs 11/68, P > 0.05; 15/70 vs 13/68, P > 0.05, respectively). The LVEFs of TMZ group at Days 30 and 180 were significantly superior to the control group (51 +/- 8)% vs (45 +/- 7)%, P < 0.05; (56 +/- 7)% vs (49 +/- 8)%, P < 0.05, respectively). CONCLUSION: Use of TMZ for patients with acute STEMI without STR after primary PCI can improve the left ventricular function at Days 30 and 180.

[Reasons and complications of pacemaker replacement operation: clinical analysis of 69 case-times].

OBJECTIVE: To analyze the reasons of cardiac permanent pacemaker replacement and the strategies to prevent relevant complications. METHODS: The clinical data of 57 patients, 38 males and 19 females, aged 74 +/- 8 (56-94), 31 with sick sinus syndrome, 26 with II or III degree atrioventricular block, who underwent 63 times of cardiac permanent pacemaker replacement, including 13 times of lead replacement, were analyzed. RESULTS: The reason of replacement included battery normal exhaustion for 57 case-times, battery exhaustion before the defined schedule for 2 case-times, lead electrodes incompletely fractured for 2 case-times, and infection of pacemaker pocket for 2 case-times. There were 9 cases of placement-related complications: pacemaker pocket hematoma (n=4), lead dislocation (n=3), and abandoned leads falling into the right ventricle (n=2). The average lifetime of old pacemakers was 9. 25 years (2 -15 years). The pacing threshold of ventricular leads after pacemaker replacement was (0.77 +/- 0. 40)V, significantly higher than the initial pacing threshold [(0.60 +/- 0.21)V, P < 0.01]. There were no significant differences in the lead impedance and R wave amplitude between the pacemaker replacement and initial implantation [(854 +/- 136)omega vs. (828 +/- 176)omega, and (12 +/- 4)mV vs. (12 +/- 4)mV, both P > 0.05]. CONCLUSION: The main reason of pacemaker replacement is battery exhaustion. Most implanted ventricular leads still can be used. A rare serious complication of cardiac pacemaker replacement operation is abandoned lead falling into the right ventricle, and correct disposing of initial leads help avoid this complication .