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.

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.

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.

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.

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.

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.

[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.

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.

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.

[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 intracoronary administration of anisodamine on slow reflow phenomenon following primary percutaneous coronary intervention in patients with acute myocardial infarction.

BACKGROUND: Many basic and clinical studies have proved that anisodamine can produce significant effect on relieving microvascular spasm, improving and dredging the coronary microcirculation. It may be beneficial to the improvement of slow-reflow phenomenon (SRP) following percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). So we investigated the effect of intracoronary administration of anisodamine on SRP of infarct related artery (IRA) following primary PCI in patients with ST segment elevated acute myocardial infarction (STEAMI). METHODS: Twenty-one patients with SRP from a total of 148 STEAMI patients accepted primary PCI were enrolled into this study from September 2004 to December 2005. When SRP happened, nitroglycerin (200 microg) was "bolus" injected firstly into IRA to exclude the spasm of epicardial artery and identify SRP as well as a baseline and self-control agent following PCI. Ten minutes later, 1000 microg of anisodamine was injected into IRA with SRP at 200 microg/s, while the coronary angiography (CAG) was taken before and at 1st, 3rd and 10th minute after administration of nitroglycerin or anisodamine, respectively. The corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG) and the diameter of IRA were calculated and analyzed by Gibson's TIMI frame count method using quantitative computer angiography (QCA) system to evaluate the influence of anisodamine on coronary flow and vessel lumen. In the meantime the invasive hemodynamic parameters of intracoronary and systemic artery (systolic, diastolic and mean pressure) and electrocardiogram (ECG) were measured and monitored. The changes of ventricular performance parameters and the adverse reaction were evaluated and followed-up at 1 month post-PCI. RESULTS: No significant changes in cTFCs and TMPGs were found at 1st, 3rd and 10th minute after intracoronary administration of nitroglycerin as compared with the baseline control (P > 0.05). cTFCs were decreased by 58.3%, 56.2%, and 54.6%, respectively (P < 0.001), and TMPGs were increased from 1.13 +/- 0.21 grade to 2.03 +/- 0.32, 2.65 +/- 0.45 and 2.51 +/- 0.57 grades (P < 0.05) at 1st, 3rd and 10th minute after intracoronary administration of anisodamine as compared with those after intracoronary administration of nitroglycerine, respectively. The average coronary blood flow of TIMI grade was improved from 1.76 +/- 0.43 to 2.71 +/- 0.46 (P < 0.05) while the diameter of middle segment in re-patented coronary artery was slightly increased from (3.20 +/- 0.40) mm to (3.40 +/- 0.50) mm at the 3rd minute after intracoronary administration of anisodamine (P > 0.05) as compared with those of nitroglycerine control. The systolic, diastolic and mean pressures of intracoronary artery after intracoronary administration of anisodamine increased from 115 to 123, 75 to 84, 88 to 95 mmHg (P < 0.05), respectively, along with the rise of heart rate from 68 to 84 beats per minute (P < 0.05). There were no significant changes in intervals of PR, QT and QRS (P > 0.05) and no any severe fast arrhythmia after intracoronary administration of anisodamine. The ventricular performance parameters were significantly improved and no major adverse cardiovascular events (MACE) were found during follow-up at 1 month post-PCI. CONCLUSIONS: Intracoronary administration of 1000 microg anisodamine is effictive in reversing SRP following PCI in STEAMI patients, especially it is suitable for SRP patients with bradycardia or hypotension.

[Influence of intracoronary administration of anisodamine on no-reflow, ventricular function and systolic synchrony in acute myocardial infarction patients undergoing percutaneous coronary intervention].

OBJECTIVE: To evaluate the influence of intracoronary administration of anisodamine on myocardial blush grade (MBG) and left ventricular regional and global systolic function and synchrony in the acute myocardial infarction (AMI) patients with no-reflow phenomenon post percutaneous coronary intervention (PCI). METHODS: Forty-seven AMI patients who underwent PCI within 12 hours of onset and MBG was 0 - 1 were randomized to receive standard therapy [group B, n = 23, 18 males, mean age (62.72 +/- 11.48) years] or standard therapy plus intracoronary administration of anisodamine [200 microg/ml, group A, n = 24, 18 males, mean age (64.23 +/- 12.27) years]. The left ventriculography (LVG) was performed immediately and 6 months after PCI to measure the ventricular volume, 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 regional, global systolic function and systolic synchrony. Incidence of major adverse cardiac events (MACE) during the follow-up was analyzed. RESULTS: Anisodamine [(2530 +/- 340) microg/person)] was well tolerated by patients. The MBG remained unchanged in group B and significantly increased from grade 0.74 +/- 0.32 to grade 2.33 +/- 0.28 10 min after anisodamine injection in group B. Six months post PCI, LVESVI [(40.53 +/- 8.12) ml/m(2) vs. (50.32 +/- 8.26) ml/m(2)], LVEDVI [(80.13 +/- 9.74) ml/m(2) vs. (87.17 +/- 10.25) ml/m(2)], WMS [(8.24 +/- 1.31) vs. (10.23 +/- 1.82)] and LVEDP [(13.36 +/- 4.21) vs. (16.38 +/- 3.21) mm Hg, 1 mm Hg = 0.133 kPa] were significantly lower in group A compared with that in group B (all P < 0.05) while LVEF [(44.02 +/- 5.86)% vs. (38.52 +/- 5.18)%], PER [(1.86 +/- 0.09) EDV/s vs. (1.61 +/- 0.09) EDV/s] and PFR [(2.19 +/- 0.32) EDV/s vs. (1.78 +/- 0.17) EDV/s] measured by ERNA were significantly increased in group A compared with that in group B (all P < 0.05). (2) LrEF(2)-LrEF(8) in group A were higher by 13.96%, 25.02%, 30.36%, 22.86%, 27.67%, 22.07% and 18.71% respectively compared with that in group B. (3) Phase analysis showed that the left ventricular systolic synchrony parameters PS [(46.04 +/- 8.93) degrees vs. (53.19 +/- 162) degrees ], FWHM [(23.02 +/- 6.27) degrees vs. (25.02 +/- 5.31) degrees ] and PSD [(7.92 +/- 4.12) degrees vs. (11.76 +/- 4.11) degrees ] were also significantly lower in group A than that in group B (all P < 0.05). (4) During the 6 months of follow-up, the incidence of MACE in group A was significantly lower than that in group B (P < 0.05). CONCLUSION: Intracoronary administration of anisodamine is safe and could partly attenuate the no-reflow phenomenon, improve the left ventricular systolic function and synchrony and reduce the incidence of MACE in patients with no-reflow phenomenon post AMI-PCI.

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.

[Acute hemodynamic effects of intravenous recombinant human brain natriuretic peptide in patients with acute myocardial infarction complicated with heart failure].

OBJECTIVE: To compare the acute hemodynamic effects and safety of intravenous injection of recombinant human brain natriuretic peptide (rhBNP) versus intravenous nitroglycerin (NIT) in acute myocardial infarction (AMI) patients with heart failure. METHODS: On top of standard therapy, 42 consecutive patients who suffered from anterior wall AMI with heart failure [pulmonary capillary wedge pressure (PCWP) > 16 mm Hg] within 12 to 24 hours from the onset of chest pain were randomized into rhBNP group (n = 21, 1.5 microg/kg bolus intravenous injection followed by 0.0075 microg.kg(-1).mn(-1) for the first 3 hours and 0.015-0.03 microg.kg(-1).mn(-1) infusion for following 21 hours) and NIT group (n = 21, 10 to 100 microg/mn intravenous infusion for 24 hours). The hemodynamic parameters were monitored by Swan-Ganz catheter at baseline, during drug infusion and 6 hours post infusion withdraw; total urine output was also obtained. The major adverse cardiac events (MACE) were observed up to 1 week after drug infusions. RESULTS: Central venous pressure and systolic blood pressure remained unchanged after rhBNP or NIT infusion. Compared to baseline level, PCWP was significantly reduced by 48.9% (P < 0.01) at 30 minutes after rhBNP infusion and this effect remained up to 6 hours post infusion withdraw; PCWP reduced by 28.7% (P < 0.05) at 2 hours after NIT infusion and this effect remained to 6 hours before infusion withdraw. Cardiac index (CI) was increased by 27.1% (P < 0.05) at 1 hour after rhBNP infusion and remained till 6 hours post infusion withdraw; CI was significantly increased at 3 hour after NIT infusion and this effect disappeared after infusion withdraw. The PCWP and CI values were significantly higher in rhBNP group than that of NIT group at 30 minutes and 2 hours (P < 0.05). Heart rate was significantly reduced at 30 minutes (95.3 +/- 7.4 vs. 118.0 +/- 8.2 bpm, P < 0.05) and at 2 hour (92.8 +/- 6.8 vs. 109.2 +/- 7.6 bpm, P < 0.05) in rhBNP and NIT group, respectively and heart rate remained reduced during the whole infusion period in both groups. The total urine output for 30 hours in rhBNP group (1870 +/- 535 ml) tended to be higher than that in NIT group (1538 +/- 620 ml, P > 0.05). There was no symptomatic hypotension or other adverse events during drug infusion in both groups and MACE up to 1 week post drug infusion was also similar between the two groups. CONCLUSION: Intravenous injection of rhBNP results in more rapid and long-lasting hemodynamic improvements than that of NIT in AMI patients with heart failure and it is also feasible and safe for clinic use in AMI patients with heart failure.

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.

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.