The effect and mechanism of dl-3-n-butylphthalide on angiogenesis in a rat model of chronic myocardial ischemia.

OBJECTIVE: To assess the effect of dl-3-n-butylphthalide (NBP) on angiogenesis and its underlying mechanism in a rat model of chronic myocardial ischemia (CMI). METHODS: Forty Sprague-Dawley rats were randomly divided into four groups: model, low-dose NBP (L-NBP), middle-dose NBP (M-NBP), or high-dose NBP (H-NBP) (n=10/group). All groups received intraperitoneal injections of isoprinosine hydrochloride daily for 14 days. Additionally, the L-NBP, M-NBP, and H-NBP groups received NBP at 3, 6, and 12 mg per kg body weight, respectively, by intraperitoneal injection. An additional 10 rats (control group) received 0.9% sodium chloride via intraperitoneal injection for 14 consecutive days. Echocardiography was used for the measurement of heart function. Immunohistochemical staining for factor VIII-related antigen and microvascular density determination were performed. The protein and mRNA expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in CMI areas were measured by western blot and RT-PCR, respectively. RESULTS: Electrocardiograms showed that NBP improved cardiac function by regulating left ventricular end-diastolic and end-systolic diameters, ejection fraction, and fractional shortening. Compared with the control and model groups, the L-NBP, M-NBP, and H-NBP groups showed increased mRNA and protein expression of VEGFA and HIF-1α in myocardial tissue. The mRNA and protein expression of VEGFA and HIF-α in the H-NBP group were the highest. CONCLUSION: NBP treatment promotes VEGF and HIF-1α protein expression during myocardial ischemia, which may represent useful biomarkers for coronary collateral establishment and offer potential targets for therapeutic induction of angiogenesis in patients with CMI.

Different dosage regimens of nifedipine, labetalol, and hydralazine for the treatment of severe hypertension during pregnancy: a network meta-analysis of randomized controlled trials.

OBJECTIVES: This network meta-analysis aimed to compare the efficacy and safety of intravenous (IV) hydralazine, oral nifedipine, and IV labetalol with different dosage regimens in the treatment of severe hypertension during pregnancy. METHODS: A comprehensive literature search was performed on PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) exploring the effects of hydralazine, nifedipine, and labetalol in the treatment of severe hypertension during pregnancy. RESULTS: A total of 21 RCTs with 2183 patients comparing 7 regimens (oral nifedipine 50,60,90 mg; hydralazine 15,25 mg; and labetalol 220,300 mg) were identified. Compared with IV labetalol 300 mg, nifedipine 50,60, and 90 mg significantly improved the successful treatment rate of severe hypertension during pregnancy, nifedipine 50 and 90 mg and IV hydralazine 25 mg required significantly fewer doses to achieve target blood pressure (BP), and nifedipine 50 mg took significantly shorter time to achieve target BP. Subgroup analysis showed that only nifedipine 50 mg tablets, not capsules, required a significantly shorter time and fewer doses to achieve target BP than IV labetalol 300 mg. Moreover, nifedipine 60,90 mg showed superior effectiveness than IV hydralazine 15,25 mg in the successful treatment rate of severe hypertension during pregnancy. SUCRA analysis suggested that nifedipine 50,60,90 mg as the better regimens with the lower rates of overall ADR and neonatal complications. CONCLUSION: These findings demonstrated the superiority of oral nifedipine 50,60,90 mg, especially oral nifedipine 50 mg tablets, in the treatment of severe hypertension during pregnancy than IV labetalol 300 mg, while oral nifedipine 60,90 mg also showed superiority in the successful treatment rate of severe hypertension during pregnancy than IV hydralazine 15,25 mg. However, the limitations of the underlying data indicate that future large-scale and rigorous RCTs are needed to confirm such findings.

Effects of Levosimendan on Right Ventricular Function in Patients with Acute Decompensated Heart Failure.

BACKGROUND: To investigate the effects of levosimendan on right ventricular (RV) function in patients with acute decompensated heart failure (ADHF). METHODS: Patients with ADHF admitted from January 2017 to October 2017 were enrolled in this study. The patients were randomized to receive 24-h intravenous levosimendan or placebo. Echocardiographic examinations were performed and the parameters were compared. Epidemiological data were recorded and compared before and after treatment. Major adverse cardiac events during hospitalization and during 1-month follow-up were compared. RESULTS: The baseline characteristics were comparable. After 24-h infusion of levosimendan and placebo, the left ventricular ejection fraction and S' were significantly increased in the levosimendan group compared with the control group (both p < 0.05). The E value in the levosimendan group significantly decreased (75.38 ± 8.32 vs. 88.21 ± 10.36, p < 0.0001), and E/e' significantly increased in the control group (19.61 ± 6.52 vs. 27.58 ± 8.22, p < 0.0001). The levels of right ventricular fractional area change (24 ± 3 vs. 20 ± 2, p < 0.0001) and tricuspid annular plane systolic excursion (1.56 ± 0.36 vs. 1.38 ± 0.21, p < 0.0001) were significantly higher in the levosimendan group than in the control group. After treatment, the values of systolic pulmonary artery pressure (SPAP) decreased in both groups (both p < 0.05), and the value of SPAP in the levosimendan group was lower than that in the control group (47.22 ± 5.6 vs. 55.85 ± 7.41, p < 0.0001). After 1-month follow-up, there was no significance in readmissions due to recurrent heart failure. CONCLUSIONS: Levosimendan seems to provide more beneficial effects among patients with ADHF to improve RV function, along with a decrease in pulmonary pressure.

Comparative Effectiveness of Taxane-Containing Regimens for Treatment of HER2-Negative Metastatic Breast Cancer: A Network Meta-analysis.

STUDY OBJECTIVES: To compare the effectiveness of different taxane-containing regimens and to identify the best strategy for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). DESIGN: Network meta-analysis of 20 randomized controlled trials (RCTs). PATIENTS: A total of 6577 patients with HER2-negative MBC who received treatment (20 different regimens) with taxanes (paclitaxel [4267 patients] or docetaxel [2310 patients]). MEASUREMENTS AND MAIN RESULTS: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched (through March 2019) for RCTs that evaluated any taxane-containing regimens for the treatment of HER2-negative MBC. A network meta-analysis in a Bayesian framework was performed using the random-effects model. We compared the surface under the cumulative ranking (SUCRA) curve for each regimen. Overall, paclitaxel-based combinations were superior to paclitaxel alone in objective response rate (ORR) (odds ratio 1.60, 95% credible interval [CrI] 1.15-2.16) and overall survival (OS) (hazard ratio 1.08, 95% CrI 1.01-1.15). Docetaxel-based combinations were also superior to paclitaxel alone in ORR. Among the paclitaxel-based regimens, based on the results of SUCRA, paclitaxel + bevacizumab + capecitabine was likely to be the most efficacious in improving ORR, OS, and progression-free survival (PFS), whereas paclitaxel + gemcitabine was likely to be the most efficacious in 1-year OS rate. Among the docetaxel-based regimens, based on the results of SUCRA, docetaxel + gemcitabine was likely to be the most efficacious in improving PFS and OS. CONCLUSION: These findings demonstrated that paclitaxel-based combinations can provide significant improvement in ORR and OS compared with paclitaxel alone. The regimens of paclitaxel + bevacizumab + capecitabine, docetaxel + gemcitabine, and paclitaxel + gemcitabine may be superior to other regimens for the treatment of HER2-negative MBC.

Comparison of myocardial microcirculatory perfusion after catheter-administered intracoronary thrombolysis with anisodamine versus standard thrombus aspiration in patients with ST-elevation myocardial infarction.

OBJECTIVE: To evaluate efficacy, safety and feasibility of targeted intracoronary injection using pro-urokinase combined with anisodamine (TCA) versus thrombus aspiration (TA) in ST-elevation myocardial infarction (STEMI) patients with high thrombus loads. BACKGROUND: The best method of avoiding thrombus detachment and stroke in PCI patients with high thrombus loads has not yet been established. METHODS: STEMI patients receiving coronary artery angiography or percutaneous coronary intervention (CAG/PCI) with thrombus grade ≥ 3 from January 1, 2017 to June 30, 2018 were randomly assigned to targeted intracoronary thrombolysis (pro-urokinase and anisodamine via catheter (TCA) group), or the TA group which followed the standard thrombus aspiration procedure. Parameters compared included thrombus grade, index of microcirculatory resistance (IMR), postoperative myocardial SPECT, thrombosis in myocardial infarction (TIMI) scores including flow grade, corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grade (TMPG). Adverse events were followed up within 3 months. RESULTS: Thirty-nine patients were finally enrolled. In primary CAG/PCI, the TCA group had higher percentages of TIMI 3 flow and lower IMR values compared with the TA group. The ratio of TMPG 3 grade in the TCA group was higher in repeat CAG, and the perfusion descending area (PDA) presented by SPECT was lower than in the TA group. No significant difference was seen in major adverse coronary events (MACEs) or bleeding events at follow-up. CONCLUSIONS: TCA appears to be effective, safe, and feasible for repatency and reduction of high thrombus burden in primary PCI and may protect myocardial microcirculation with improved outcomes.

Arctigenin Attenuates Ischemia/Reperfusion Induced Ventricular Arrhythmias by Decreasing Oxidative Stress in Rats.

BACKGROUND/AIMS: Arctigenin (ATG) has been shown to possess anti-inflammatory, immunemodulatory, anti-viral, anti-microbial, anti-carcinogenic, vasodilatory and anti-platelet aggregation properties. However, the protective role of ATG in prevention of arrhythmias induced by myocardial ischemia/reperfusion is unknown. The aim of this study was to investigate the anti-arrhythmia effect of ATG in an ischemia/reperfusion injured rat heart model and explore the related mechanisms. METHODS: Rats were randomly exposed to sham operation, myocardial ischemia/ reperfusion (MI/R) alone, ATG+ MI/R, pretreated with ATG in low (12.5 mg/kg/day), medium (50 mg/kg/day) and high dose (200 mg/kg/day), respectively. Ventricular arrhythmias were assessed. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde (MDA) in myocardial tissue were determined by chemical analysis. RESULTS: Compared to MI/R, rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/day showed significantly reduced incidence and duration of ventricular fibrillation, ventricular tachycardia and ventricular ectopic beat (VEB), and decreased the arrhythmia score during the 30-min ischemia. Incidence and duration of ventricular tachycardia, infarction size and arrhythmia scores in these groups were significantly decreased during the 120-min reperfusion. No ventricular fibrillation occurred during the period of reperfusion. Rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/ day markedly enhanced the activities of antioxidant enzymes SOD and GSH-Px, reduced the level of MDA. No differences were observed between the group pretreated with a low dose of ATG and the sham group. Administration of ATG significantly increased the expression of antioxidant stress protein Nrf2, Trx1 and Nox1. CONCLUSION: Our data suggested that ATG plays anti-arrhythmia role in ischemia/reperfusion injury, which is probably associated with attenuating oxidative stress by Nrf2 signaling pathway.

Effects of intensive pitavastatin therapy on glucose control in patients with non-ST elevation acute coronary syndrome.

Objective: This study aimed to investigate the effects of intensive pitavastatin therapy on glucose control in patients with non-ST elevation acute coronary syndrome (ACS). Methods: Patients who had ACS with significant stenosis on initial coronary angiography and received successful percutaneous coronary intervention (PCI) in the Second Hospital of Hebei Medical University, Shijiazhuang, China from August 2015 to January 2016 were enrolled in this study. The patients were randomized to receive pitavastatin (4 mg daily) or atorvastatin (20 mg daily). PCI was performed within 72 hours after admission according to the current clinical practice at the physician's discretion. The examinations of blood lipid levels and blood markers of glucose metabolism were performed at baseline and after 6-month follow-up using standard techniques. The inflammatory markers, including white blood cell, high-sensitivity C-reactive protein (hs-CRP) and fibrinogen, were also assessed before PCI and 24 hours after PCI. An independent adverse event assessment committee evaluated major adverse cardiovascular events (MACE) and any other adverse events. Results: A total of 132 patients were enrolled and randomly divided into the pitavastatin group (n = 65) or the atorvastatin group (n = 67), which had similar baseline characteristics and PCI procedural characteristics. For the inflammatory biomarkers at 24 hours after PCI, the fibrinogen level was significantly increased in the atorvastatin group; the hs-CRP levels were significantly increased in both groups, however, the hs-CRP level in the pitavastatin group was lower than that in the atorvastatin group. In addition, the blood lipid parameters (e.g., TC, LDL-C, TG, non-HDL-C and Apo B) were significantly decreased in both groups after 6-month follow-up (P < 0.01), but these parameters between the two groups had no significant difference. After 6-month follow-up, the FPG, IRI, HOMA-IR and HbA1c levels were significantly decreased in the pitavastatin group (P < 0.05) but slightly increased in the atorvastatin group, indicating that the glucose homeostasis was improved in patients in the pitavastatin group but not in the atorvastatin group. Furthermore, the incidence of MACE was not significantly different between the two groups (P > 0.05). After 6-month antiplatelet treatment, the PAR value was significantly decreased in both groups (P < 0.01), but the PAR value in the pitavastatin group was lower than that in the atorvastatin group. Conclusion: Pitavastatin therapy may improve the glucose homeostasis for patients with ACS undergoing PCI and has more favorable outcomes than atorvastatin therapy.

Efficacy and Safety of Pulmonary Arterial Hypertension-specific Therapy in Pulmonary Arterial Hypertension: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Previous meta-analyses of pulmonary arterial hypertension (PAH)-specific therapy for PAH pooled PAH-specific combination therapy and monotherapy. This flaw may threaten the authenticity of their findings. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials that evaluated any PAH-specific medications in the treatment of PAH. We calculated ORs with 95% CIs for dichotomous data and standardized mean differences for continuous data. RESULTS: In total, 35 randomized controlled trials involving 6,702 patients were included. In monotherapy vs placebo/conventional therapy, significance was obtained in mortality reduction (OR, 0.50 [95% CI, 0.33 to 0.76]; P = .001), 6-min walk test (mean difference, 31.10 m [95% CI, 25.40 to 36.80]; P < .00001), New York Heart Association/World Health Organization functional class (OR, 2.48 [95% CI, 1.51 to 4.07]; P = .0003), and hemodynamic status based on mean pulmonary artery pressure, pulmonary vascular resistance, cardiac index, and incidence of withdrawal due to adverse effects. In combination therapy vs monotherapy, significance was reached for the 6-min walk test (mean difference, 19.96 m [95% CI, 15.35 to 24.57]; P < .00001), functional class (OR, 1.65 [95% CI, 1.20 to 2.28]; P = .002), hemodynamic status, and incidence of withdrawal due to adverse effects (OR, 2.01 [95% CI, 1.54 to 2.61]; P < .00001) but not for mortality reduction (OR, 0.98 [95% CI, 0.57 to 1.68]; P = .94). CONCLUSIONS: Our meta-analysis revealed that PAH-specific monotherapy could improve mortality, exercise capacity, functional class, and hemodynamic status compared with placebo or conventional therapy. However, combination therapy could further improve exercise capacity, functional class, and hemodynamic status compared with monotherapy, but it had no proven effect on mortality. Combination therapy had a much higher incidence of withdrawal due to adverse effects than monotherapy.

Comparative efficacy and safety of OADs in management of GDM: network meta-analysis of randomized controlled trials.

OBJECTIVE: We conducted a network meta-analysis to evaluate the efficacy and safety of oral antidiabetic drugs (OADs) for gestational diabetes. DATA SOURCES: We searched PubMed, the Cochrane Library, ClinicalTrials.gov, and related reviews from inception to October 2014. STUDY SELECTION: We included randomized clinical trials comparing efficacy and safety between different OADs or OADs vs insulin in patients with gestational diabetes. DATA SYNTHESIS: We included 18 randomized clinical trials. Traditional and network meta-analyses were performed to compare different OADs or OADs vs insulin. Traditional meta-analyses confirmed that there was no significant difference in maternal fasting blood glucose or glycated hemoglobin levels in patients treated with insulin, metformin, and glyburide. Compared to insulin, metformin was associated with lower maternal weight gain (weighted mean difference [WMD], -1.49 kg; 95% confidence interval [CI], -2.26 to -0.31), shorter gestational age (WMD, -0.16 wk; 95% CI, -0.30 to -0.03), and increased incidence of premature birth (odds ratio [OR], 1.63; 95% CI, 1.07 to 2.48). Compared to insulin, glyburide was associated with higher neonatal birth weight (WMD, 130.68 g; 95% CI, 55.98 to 205.38), increased incidence of neonatal hypoglycemia (OR, 2.64; 95% CI, 1.59 to 4.38), and increased incidence of macrosomia (OR, 3.09; 95% CI, 1.59 to 6.04). Network meta-analysis revealed that glyburide was associated with higher maternal weight gain, higher neonatal birth weight, increased incidence of neonatal hypoglycemia, and increased incidence of macrosomia than was metformin. CONCLUSION: Both metformin and glyburide are suitable for use in the management of gestational diabetes because of good glycemic control. However, glyburide treatment is associated with increased risk of neonatal hypoglycemia, high maternal weight gain, high neonatal birth weight, and macrosomia.

Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials.

OBJECTIVE: The use of thiazolidinediones (TZDs) has been associated with increased fracture risk. We performed a comprehensive literature review and meta-analysis to estimate the risk of fractures with TZDs METHODS: We searched MEDLINE, Embase and the Cochrane Database, from inception to May 2014. We included all randomized trials that described the risk of fractures or changes in bone mineral density (BMD) with TZDs. We pooled data with odds ratios (ORs) for fractures and the weighted mean difference in BMD. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I(2) statistic. RESULTS: We included 24,544 participants with 896 fracture cases from 22 randomized controlled trials. Meta-analysis showed that the significantly increased incidence of fracture was found in women (OR=1.94; 95%CI: 1.60-2.35; P<0.001), but not in men (OR=1.02; 95%CI: 0.83-1.27; P=0.83). For women, the fracture risk was similar in rosiglitazone (OR=2.01; 95%CI: 1.61-2.51; P<0.001) and pioglitazone (OR=1.73; 95%CI: 1.18-2.55; P=0.005) treatment and appeared to be similar for participants aged <60years old (OR=1.89; 95%CI: 1.51-2.36; P<0.001) and aged ≥60years old (OR=2.07; 95%CI: 1.51-2.36; P<0.001). There was a non-significant trend towards increased risk of fractures in different cumulative durations of TZD exposure. TZD treatment was also associated with significant changes in BMD among women at the lumbar spine(weighted mean difference: -0.49%, 95%CI: -0.66% to -0.32%; P<0.001), the femoral neck (weighted mean difference: -0.34%, 95%CI: -0.51% to -0.16%; P<0.001) and the hip(weighted mean difference: -0.33%, 95%CI: -0.52% to -0.14%; P<0.001). CONCLUSIONS: Our results suggest that TZD treatment is associated with an increased risk of fractures in women, effects of rosiglitazone and pioglitazone are similar, fracture risk is independent of age and fracture risk has no clear association with duration of TZD exposure.

Thrombolysis Followed by Early Percutaneous Coronary Intervention via Transradial Artery Approach in Patients with ST-Segment Elevation Infarction.

BACKGROUND: The purpose of this study was to investigate the safety and efficacy of thrombolysis followed by early percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 161 patients were enrolled in the study. Fifty-three of them who underwent thrombolysis in non-PCI hospital and immediately transferred to receive early PCI were assigned to the early PCI group (E-PCI); the rest of the patients were assigned to the primary PCI group (P-PCI). Coronary angiography and PCI were performed via the transradial artery approach for patients in both groups. Angiographic parameters, bleeding complications and total hospital stay were compared between the two groups. All patients were followed-up for 30 days to evaluate major adverse cardiac events (MACE). RESULTS: Before PCI procedure, the thrombus score of IRA in the E-PCI group was lower, and the percentage of TIMI flow grade (TFG) 3 was higher (both p < 0.05) compared to those in the P-PCI group. The myocardial reperfusion in the E-PCI group was better than that in the P-PCI group. There was a trend towards a lower peak value of serum creatine kinase MB in the E-PCI group, and left ventricular ejection fraction (LVEF) before discharge in E-PCI was higher than that in the P-PCI group (54.38 ± 5.29% vs. 52.19 ± 7.00%, respectively, p = 0.028). No significant differences were found in the incidences of bleeding complications and hospital stay between the two groups. There was no significant difference in the 30-day MACE between the two groups (p = 0.863), and no significance of cumulative MACE-free survival rates were found between the two groups as well (p = 0.522). Variables predicting MACE upon patient follow-up according to univariable Cox regression analyses showed that a history of hyperlipidemia, smokers, TFG of infarction related artery before PCI < 2, and low levels of LVEF were associated with poor clinical outcomes (all p < 0.05). CONCLUSIONS: It is safe and efficacious for STEMI patients to receive thrombolysis followed by early PCI via the transradial artery approach. KEY WORDS: Major adverse cardiac event; Percutaneous coronary intervention; Radial artery; ST-segment elevation myocardial infarction; Thrombolysis.

Intracoronary fixed dose of nitroprusside via thrombus aspiration catheter for the prevention of the no-reflow phenomenon following primary percutaneous coronary intervention in acute myocardial infarction.

Previous studies have shown that intracoronary (IC) nitroprusside (NTP) injection is a safe and effective strategy for the treatment of no-reflow (NR) during percutaneous coronary intervention (PCI). The present study tested the hypothesis that, on the basis of thrombus aspiration for the treatment of ST-segment elevation myocardial infarction (STEMI), the selective IC administration of a fixed dose of NTP (100 µg) plus tirofiban is a safe and superior treatment method compared with the IC administration of tirofiban alone for the prevention of NR during primary PCI. A total of 162 consecutive patients with STEMI, who underwent primary PCI within 12 h of onset, were randomly assigned to two groups: Group A, IC administration of a fixed dose of NTP (100 µg) plus tirofiban (10 µg/kg) and group B, IC administration of tirofiban (10 µg/kg) alone (n=80 and n=82, respectively). The drugs were selectively injected into the infarct-related artery (IRA) via a thrombus aspiration catheter advanced into the IRA. The primary end-point was post-procedural corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). The proportion of complete (>70%) ST-segment resolution (STR); the TIMI myocardial perfusion grade (TMPG) 2-3 ratio following PCI; the peak value of creatine kinase (CK)-MB; the TIMI flow grade; the incidence of major adverse cardiac events (MACEs) and the left ventricular ejection fraction (LVEF) after 6 months of follow-up were observed as the secondary end-points. There were no significant differences in the baseline clinical and angiographic characteristics between the two groups. Compared with group B, group A had i) a lower CTFC (23±7 versus 29±11, P=0.000); ii) a higher proportion of complete STR (72.5 versus 55.9%, P=0.040); iii) an enhanced TMPG 2-3 ratio (71.3 versus 53.7%, P=0.030) and iv) a lower peak CK-MB value (170±56 versus 210±48 U/l, P=0.010). There were no statistically significant differences in the final TIMI grade-3 flow between the two groups (92.5 versus 91.5% for groups A and B, respectively; P=0.956). The LVEF at 6 months was higher in group A than group B (63±9 versus 53±11%, respectively; P=0.001); however, the incidence of MACEs was not statistically different between the two groups, although there was a trend indicating improvement in group A (log rank χ2=0.953, P=0.489). The selective IC administration of a fixed dose of NTP (100 µg) plus tirofiban via a thrombus aspiration catheter advanced into the IRA is a safe and superior treatment method compared with tirofiban alone in patients with STEMI undergoing primary PCI. This novel therapeutic strategy improves the myocardial level perfusion, in addition to reducing the infarct size. Furthermore, it may improve the postoperative clinical prognosis following PCI.

Preventive effects of anisodamine against contrast-induced nephropathy in type 2 diabetics with renal insufficiency undergoing coronary angiography or angioplasty.

BACKGROUND: Anisodamine is widely used in therapy for treating acute glomerulonephritis and diabetic nephropathy because it can improve renal microcirculation. We performed a study to evaluate the preventive effects of anisodamine against contrast-induced nephropathy (CIN) in type 2 diabetics with renal insufficiency undergoing coronary angiography or angioplasty. METHODS: A total of 260 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) of 60 ml(-1)×min(-1)×1.73 m(-2) or less, who were undergoing coronary angiography or angioplasty, were randomly assigned to receive an infusion of either sodium chloride (control group, n = 128) or anisodamine (treatment group, n = 132). Patients in the treatment group received an infusion of anisodamine at a rate of 0.2 µg×kg(-1)×min(-1) from 12 hours before to 12 hours after coronary angiography or angioplasty, while patients in the control group received an infusion of sodium chloride with the same volume as the treatment group. All patients received intravenous sodium chloride hydration. CIN was defined as a 25% increase in serum creatinine from baseline or an absolute increase of > 0.5 mg/dl within three days after contrast exposure. The primary end point was the incidence of CIN. The secondary end point was a 25% or greater reduction in eGFR. RESULTS: There were no significant differences between the two groups with regard to age, gender, risk factors, laboratory results, medications and interventions. The incidence of CIN was 9.8% (13/132) in the treatment group and 20.3% (26/128) in the control group (P < 0.05). The secondary end point was 6.0% (8/132) in the treatment group and 16.4% (21/128) in the control group (P < 0.05). CONCLUSION: These results indicate the preventive effects of anisodamine against CIN in type 2 diabetics with renal insufficiency who are undergoing coronary angiography or angioplasty.

Randomized comparison of radial versus femoral approach for patients with STEMI undergoing early PCI following intravenous thrombolysis.

BACKGROUND: Early percutaneous coronary intervention (PCI) following thrombolysis may be beneficial in patients with ST-segment elevation myocardial infarction (STEMI) who were admitted at a non-PCI hospital. The aim of this study was to evaluate the safety and efficacy of the radial artery as a vascular route for early PCI following thrombolysis in patients with STEMI. METHODS: All consecutive STEMI patients within 12 hours after thrombolysis were enrolled, and eligible patients were randomly assigned to either transfemoral (TFI group) or transradial catheterization (TRI group). Several time intervals were measured. The puncture success rate and ambulation time were assessed. The vascular access-site complications were also assessed after the PCI procedure, and the incidence of major adverse cardiac events (MACE) in hospital was observed. RESULTS: A total of 119 cases were enrolled, with 60 in the TRI group and 59 in the TFI group. There were no significant differences in transfer time and total procedure time. The puncture time in the TRI group was not significantly different compared to the TFI group. The time between PCI and ambulation in the TRI group was shorter than in the TFI group. There was a trend toward lower in the incidence of bleeding complications and vascular complications in the TRI group. CONCLUSION: TRI for STEMI patients following intravenous thrombolysis was as safe and feasible as TFI, with a trend toward lower incidence of bleeding complications and vascular complications.

Safety and efficacy of anisodamine on prevention of contrast induced nephropathy in patients with acute coronary syndrome.

BACKGROUND: Previous studies have proved the renal protective effects of anisodamine in patients with septic shock. The aim of this study was to investigate anisodamine for the prevention of contrast induced nephropathy (CIN) in patients with acute coronary syndrome (ACS). METHODS: Consecutive ACS patients undergoing elective percutaneous coronary intervention (PCI) were randomly assigned to one of two groups: patients in the anisodamine group (ANI group) were assigned to receive intravenous infusions of anisodamine by an adjusted-dose (0.1 - 0.2 µg × kg(-1)× min(-1)) from the PCI procedure to 24 hours after PCI, and the control group (CON group) received 0.9% isotonic saline of the same volume. All patients were hydrated for 6 to 12 hours before and 12 hours after PCI. Blood samples were taken on the day of PCI and at 24, 48 and 72 hours after PCI to measure the serum creatinine (SCr). RESULTS: A total of 177 patients were involved in the study, 88 in the ANI group and 89 in the CON group. In both groups, the SCr concentrations significantly increased after PCI, with the peak value occurring at 48 hours. At 72 hours, the SCr concentration in the ANI group retuned to the baseline level (P > 0.05), but the SCr concentration in CON group was still higher than baseline level (P < 0.01). The SCr concentrations at 48 and 72 hours after PCI were much lower in the ANI group than those in the CON group (both P < 0.01). The estimated glomerular filtration rate (eGFR) significantly decreased after PCI, the lowest value occurred at 48 hours. In the ANI group, the eGFR at 72 hours was similar to the baseline level. In the CON group, the eGFR failed to return to baseline at 72 hours (P < 0.01). The eGFR at 24, 48 and 72 hours after PCI were higher in the ANI group (all P < 0.05). The incidence of CIN in the ANI group was lower than that in the CON group within 72 hours after PCI (P < 0.05). The results of multiple Logistic regression proved that both diabetes and left ventricular ejection fraction (LVEF) were independent predictors of CIN, and treatment with anisodamine was an independent preventive factor of CIN (OR 0.369 and 95%CI 0.171 to 0.794, P = 0.011). No serious side effects were found in the ANI group. CONCLUSION: Intravenous infusion of anisodamine during and after elective PCI may safely prevent the occurrence of CIN in ACS patients.

Prediction of contrast-induced nephropathy in diabetics undergoing elective percutaneous coronary intervention: role of the ratio of contrast medium volume to estimated glomerular filtration rate.

BACKGROUND: Diabetic patients undergoing percutaneous coronary intervention (PCI) have a higher incidence of contrast-induced nephropathy (CIN) than nondiabetic patients, and no pharmacological approach has been demonstrated to offer consistent protection. Therefore, identifying individuals who are at increased risk becomes essential. This study was designed to assess the predictive role of the ratio of contrast medium volume to estimated glomerular filtration rate (CMV/eGFR) in diabetic patients undergoing elective PCI who developed CIN. METHODS: We retrospectively investigated clinical factors associated with the development of CIN in 114 diabetic patients who had undergone elective PCI. The risk factors for CIN included age, gender, body mass index (BMI), left ventricular ejection fraction (LVEF), hemoglobin (Hb), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), volume of contrast medium, basic levels of serum creatinine (Scr), the number of treated vessels and the number of stents used. We conducted a stepwise regression analysis to evaluate the predictive role of these risk factors in the incidence of CIN. RESULTS: The incidence of CIN was 18.4% (21/114). There were no significant differences in age, gender, BMI, LVEF, Hb, FPG, HbA1c, and incidence of hypertension and number of acute myocardial infarction (AMI) in patients between the CIN (n = 21) and the non-CIN (n = 93) groups. However, the eGFR was significantly lower ((72.0 ± 12.5) ml·min(-1)·1.73 m(-2) vs. (82.0 ± 16.5) ml·min(-1)·1.7 m(-2), P = 0.010), and the basic serum creatinine level ((1.07 ± 0.12) mg/dl vs. (0.97 ± 0.19) mg/dl P = 0.014) was significantly higher in the CIN group. In addition, the volume of contrast medium was significantly larger ((253 ± 75) ml vs. (211 ± 71) ml, P = 0.017) and the CMV/eGFR ratio was significantly greater (3.64 ± 1.26 vs. 2.70 ± 1.11, P = 0.001) in the CIN group. Stepwise regression analysis showed that the CMV/eGFR ratio was a significant independent predictor for the development of CIN (P = 0.001). At a cut-off point of > 3.1, the CMV/eGFR ratio exhibited 71% sensitivity and 70% specificity for detecting CIN. CONCLUSION: The CMV/eGFR ratio could be a valuable predictor of CIN for diabetic patients after elective PCI. At a cut-off point of > 3.1, the CMV/eGFR ratio was an optimal predictor for the incidence of CIN.

[The use of recombinant human B-type natriuretic peptide for the protection of cardiac and renal functions in heart failure patients with acute anterior myocardial infarction in peri-operative period of primary percutaneous coronary intervention].

OBJECTIVE: To evaluate the protective effect of recombinant human B-type natriuretic peptide (rhBNP) on cardiac and renal functions in heart failure (HF) patients as a result of acute anterior myocardial infarction (AAMI) in peri-operative period of primary percutaneous coronary intervention (pPCI). METHODS: One hundred and twenty-six patients with AAMI-HF were enrolled into this study. All patients undertaken pPCI were randomly assigned to the rhBNP group (n=62) or the control group (n=64). rhBNP or nitroglycerin was intravenously administered on the basis of conventional treatment from first day of admission to 24 hours after pPCI in both groups. Heart rate (HR), systolic blood pressure (SBP), B-type natriuretic peptide (BNP), estimated glomerular filtration rate (eGFR) and heart function were observed. All patients were followed up for 30 days for the observation of main adverse cardiac events (MACE). RESULTS: The HR was significantly decreased compared with that at admission in rhBNP group, but such condition was not found in the control group. The SBP was reduced obviously in both groups. The plasma level of BNP, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVEDD) were improved significantly at different time points compared with those before administration in both groups. The improvement of above parameters in rhBNP group was more significant than that in the control group [BNP (ng/L) 30 hours after pPCI: 303.5±128.4 vs. 354.0±133.6, 14 days after pPCI: 157.8±78.6 vs. 201.1±91.7; LVEF 1 day after pPCI: 0.420±0.052 vs. 0.378±0.055, 14 days after pPCI : 0.444±0.050 vs. 0.393±0.055, 30 days after pPCI: 0.469±0.053 vs. 0.413±0.052; LVEDD (mm) 1 day after pPCI: 53.5±4.4 vs. 57.6±4.4, 14 days after pPCI : 49.6±5.1 vs. 53.4±4.6, 30 days after pPCI: 46.5±4.4 vs. 50.2±4.8, P<0.05 or P<0.01]. The eGFR was reduced obviously 1 day after pPCI than that at admission in both groups, and eGFR recovered to baseline 3 days after pPCI. The level of eGFR was significantly increased 7 days and 14 days after pPCI than that at admission, but there was no difference between rhBNP group and control group. The incidence of contrast-induced nephropathy showed a lowering tendency in the rhBNP group than that in the control group [19.4% (12/62) vs. 29.7% (19/64), P=0.178]. The incidence of ventricular arrhythmias was obviously lowered 7 days after pPCI in the rhBNP group than that in the control group [48.4% (30/62) vs. 75.0% (48/64), P<0.01]. The rate of MACE was lower in rhBNP group than that in control group in 30 days [12.9% (8/62) vs. 26.6% (17/64), P<0.05]. CONCLUSION: Administration of rhBNP can effectively improve the heart function in AAMI-HF patients undergoing pPCI, and it lowered the incidence of MACE in 30 days, without influence on renal function, and it can reduce the incidence of contrast-induced nephropathy.

Intensive cholesterol lowering with statin improves the outcomes of percutaneous coronary intervention in patients with acute coronary syndrome.

BACKGROUND: The incidence of no reflow phenomenon limits the clinical outcomes of percutaneous coronary intervention (PCI). This randomized controlled study was designed to evaluate the immediate protective effects of intensive statin pretreatment on myocardial perfusion and myocardial ischemic injury during PCI. METHODS: Altogether 228 patients with acute coronary syndrome (ACS) were randomly assigned to standard statin group (SS group, n = 115) and intensive statin group (IS group, n = 113). Patients in the SS group received 20 mg simvastatin and patients in the IS group received 80 mg simvastatin for 7 days before PCI. Thrombolysis in myocardial infarction (TIMI) flow grade (TFG), corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) of the intervened vessel were recorded before and after stent deployment. Creatine kinase (CK) isoenzyme MB, troponin I and plasma level of high sensitive-C reactive protein (hs-CRP), P-selectin and intercellular adhesion molecule (ICAM) were measured before and 24 hours after the procedure. RESULTS: The TFG after stent deployment was significantly improved with less TIMI 0-1 and more TIMI 3 blood flow in the IS group than in the SS group (all P < 0.05). Patients with no reflow phenomenon were less in the IS group (P < 0.001). The CTFC was lower in the IS group than in the SS group (P < 0.001). TMPG was also improved in the IS group than in the SS group (P = 0.001). Although PCI caused a significant increase in CK-MB 24 hours after the procedure, the elevated CK-MB value was lower in the IS group than in the SS group (18.74 +/- 8.41 vs 21.78 +/- 10.64, P = 0.018). Similar changes were also found in troponin I (0.99 +/- 1.07 in the IS group vs 1.47 +/- 1.54 in the SS group, P = 0.006). CK-MB elevation occurred in 27.8% (32/115) of the patients in the SS group vs 15.9% (18/113) in the IS group (P = 0.030). Myocardial necrosis was detected in 4.4% (5/115) of the patients in the SS group, whereas 0.9% (1/113) in the IS group (P = 0.341). But no myocardial infarction was found. Similarly, the patients with increased level of troponin I were much more in the SS group (36.5%, 42/115) than in the IS group (19.5%, 22/113) (P = 0.04). Among them, myocardial necrosis was detected in 13.0% (15/115) of the patients in the SS group, while 4.4% (5/113) in the IS group (P = 0.021). Myocardial infarction was found in 4.4% (5/115) of the patients in the SS group and 0.9% (1/113) in the IS group (P = 0.213). CONCLUSIONS: Intensive statin pretreatment for 7 days before PCI can further improve myocardial blood perfusion, protect the myocardium from ischemic injury. These effects are associated with the lowered levels of hs-CRP, P-selectin and ICAM.

[Effect of urapidil on heart function and ventricular systolic synchrony in acute myocardial infarction patients with no-reflow phenomenon after percutaneous coronary intervention].

OBJECTIVE: To evaluate the influence of intracoronary administration of urapidil on myocardial blush grade (MBG) and left ventricular systolic function and synchrony in the acute myocardial infarction (AMI) patients with no-reflow phenomenon after percutaneous coronary intervention (PCI) identified by MBG. METHODS: Forty-three patients with AMI, in whom primary PCI was successfully performed (6.25+/-2.37) hours after the onset of angina pectoris,were found to have no-reflow phenomenon. They were randomized into two groups: urapidil group (n=22) and no-reflow control group (n=21). Nitroglycerin (200 microg) was injected into coronary artery. Urapidil (5 mg) was injected into coronary artery after 10 minutes in the urapidil group, and 0.9% NaCl (5 ml, weight percentage) was injected into coronary artery in the no-reflow control group. All the patients received same standard therapy afterwards. The left ventriculography (LVG) was performed immediately and 6 months after PCI to measure the ventricular volume, left ventricular end-diastolic pressure (LVEDP), and wall motion score (WMS). Equilibrium radionuclide angiography (ERNA) was performed 1 week and 6 months after PCI to determine the parameters of left ventricular systolic function and systolic synchrony. RESULTS: The MBG of urapidil group and control group was grade 0.77+/-0.31 and grade 0.77+/-0.28 after PCI, respectively. The MBG remained unchanged in control group and significantly increased from grade 0.77+/-0.31 to grade 2.37+/-0.27 10 minutes in urapidil group (P<0.05). Follow-up at 6 months after AMI-PCI, left ventricular end-systolic volume index (LVESVI), left ventricular end-diastolic volume index (LVEDVI), WMS and LVEDP were significantly lower in urapidil group compared with those in control group respectively (all P<0.05). The values of left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR) of the ERNA as measured by ERNA were significantly increased in urapidil group compared with that in control group (all P<0.05). Phase analysis showed that the left ventricular systolic synchrony parameters phase shift (PS), full width at half maximum (FWHM) and peak phase standard deviation (PSD) were also significantly lower in urapidil group than those in control group (all P<0.05). CONCLUSION: Intracoronary administration of urapidil can attenuate the no-reflow phenomenon, improve the left ventricular systolic function and synchrony in patients with no-reflow phenomenon after AMI-PCI.

Effect of tirofiban plus clopidogrel and aspirin on primary percutaneous coronary intervention via transradial approach in patients with acute myocardial infarction.

BACKGROUND: Aspirin and clopidogrel can improve myocardial reperfusion and alleviate myocardial injury during percutaneous coronary intervention (PCI). Whether the addition of intravenous tirofiban during this procedure produces further benefit has not been clarified in ST segment elevation myocardial infarction (STEMI) patients. We evaluated this on STEMI patients who underwent primary PCI (p-PCI) via transradial artery approach. METHODS: Consecutive patients were randomized into tirofiban group (n=72) or placebo group (n=78). Angiographic analysis included initial and final thrombolysis in myocardial infarction (TIMI) flow grade (TFG), corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) of the thrombotic vessel. Platelet aggregation rate (PAR), creatine phosphokinase (CPK), CPK isoenzyme MB (CPK-MB) and troponin I levels were measured and TIMI definitions were used to assess bleeding complications. Left ventricular performance parameters were investigated with equilibrium radionuclide ventriculography. Major adverse cardiac events (MACE) were followed up for 6 months. RESULTS: The cases of TFG 0 and 1 before PCI, TFG 0 when first crossing of guide wire were less, and the cases of TFG 3 after PCI was more in tirofiban group than those in placebo group. The final CTFC was fewer and the incidence of no reflow phenomenon was lower, as well the percentage of final TFG 3 was higher in tirofiban group than those in placebo group (all P<0.05). Mean peak CPK-MB was significantly lower, while the left ventricular performance parameters 1 week after PCI were much more improved in tirofiban group than those in the placebo group. PAR was significantly decreased shortly after tirofiban infusion. The incidence of 6-month MACE in tirofiban group was obviously lower than that in the placebo group. No statistical difference was noted between the two groups with regard to bleeding complications. CONCLUSIONS: Intravenous tirofiban infusion, in addition to aspirin and clopidogrel in STEMI patients with p-PCI via transradial artery access, can quickly inhibit platelet aggregation, loosen occlusive thrombus, improve myocardial reperfusion and reduce incidence of MACE with few complications of vessel access and bleeding.