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10 protocols using metoprolol tartrate

1

Coronary Artery Calcium Scoring by CT

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All patients with heart rates >70 bpm received oral β-blocker therapy, with 50 or 100 mg of metoprolol tartrate (AstraZeneca, Zoetermeer, the Netherlands) after stress testing to achieve a heart rate <70 bpm for the CAC scan. A nonenhanced CT scan (high definition CT XT; GE Healthcare) taken during breath-hold at end expiration to calculate the total CAC score was acquired with ECG triggering at 75% of the R-R interval. The scanning parameters consisted of 40 or 48 sections of 2.5-mm section thickness; gantry rotation time, 330 ms; tube voltage, 120 kV; and a tube current of 125 mA. If patients were not able to hold their breath, a free breathing CT was acquired. Post-processing was conducted at a dedicated workstation using Smartscore software (GE Healthcare). The CAC score was calculated using the standard Agatston criteria.12 (link) CAC score was categorized into three subgroups: patients with total coronary CAC score of 0, a CAC score of 1 to 300, and a CAC score of more than 300.
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2

CT Coronary Angiography Protocol

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CCTA was performed on a 256-slice CT scanner (Brilliance iCT; Philips Healthcare, Cleveland, OH, USA). In all patients with a heart rate (HR) > 65 beats per minute (bpm), a β-blocker (metoprolol tartrate; AstraZeneca, London, UK) was orally administered at the dose of 25–50 mg to achieve the target HR ≤ 65 bpm, 2 hours before CT examinations. Administration of sublingual nitroglycerin (LGC, Teddington, UK) for coronary vasodilation was performed at the time of imaging. CCTA was performed using a prospective electrocardiogram (ECG) triggering protocol using the following parameters: slice configuration, 128 × 0.625 mm; gantry rotation time, 270 ms; pitch, 0.18; tube voltage, 100 kVp; effective tube current time product, 600 mAs with ECG-dependent tube current modulation; and slice thickness, 0.8 mm with slice increment of 0.45 mm. A bolus-tracking technique was used to monitor the CT value of the ascending aorta with a trigger threshold of 120 HU. The scans were started 5 seconds after the trigger. Each patient received 70 mL of contrast media (iopromide, Ultravist® 370; Bayer Healthcare, Berlin, Germany) intravenously at the speed of 5 mL/s, followed by 40 mL of saline at the same injection speed.
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3

Vasorelaxation Effects of GXN Extract

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GXNT (powdered GXN extract, crude herb content: 12.85 g/g) were provided by Chiatai Qinchunbao Pharmaceutical Co., Ltd. (Hangzhou, China). PE (No.7161001) and NE (No. 90302) were produced by Shanghai Hefeng Pharmaceutical Co., Ltd. (Shanghai, China). The inhibitors Nw-nitro-L-arginine methyl ester (L-NAME), methylthionine chloride (MB), 4-aminopyridine (4-AP), barium chloride (BaCl2), glibenclamide (GLI), tetraethylamine (TEA), and wortmannin were purchased from Sigma (United States). Metoprolol tartrate was obtained from AstraZeneca Pharmaceutical Co., Ltd. (UK), and diltiazem hydrochloride (Dil) injection was from Takata Pharmaceutical Co., Ltd. (Japan). Kits to detect NO (No.20180302) and cGMP (No. 20180208) were provided by the Nanjing Jiancheng Bioengineering Research Institute (Nanjing, China). The calcium ion indicator Fluo-4AM (KR652) was obtained from Japan DOJINDO Chemical Technology Co., Ltd (Japan). Primary antibodies against p-eNOS (9571S), eNOS (5880S), p-Akt (9271S), Akt (4691S), β-actin (4970S), p-CaMKII (12716S), and PI3K (4249S) were purchased from Cell Signaling Technology, Inc. (United States). The composition of Krebs solution, NaCl, KCl, KH2PO4, MgSO4, NaHCO3, CaCl2, and glucose, were purchased from Sigma.
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4

Coronary Calcium Scoring Protocol

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All patients with heart rates >70 bpm received oral β-blocker therapy with 50 or 100 mg of metoprolol tartrate (AstraZeneca, Zoetermeer, Netherlands) after stress testing to achieve a heart rate <70 bpm for the CAC scan. A nonenhanced CT scan (High Definition CT XT; GE Healthcare) was performed during breath-hold at end expiration to calculate the total CACS. CACS was acquired with electrocardiogram (ECG) triggering at 75% of the R-R interval and with the following scanning parameters: 40 or 48 sections of 2.5 mm thickness, gantry rotation time of 330 ms, tube voltage of 120 kV, and a tube current of 125 mA. If patients were not able to hold their breath, a free-breathing CT was performed. Postprocessing was conducted at a dedicated workstation using SmartScore software (GE Healthcare, Milwaukee, Wisconsin, USA). The CACS was calculated using the standard Agatston criteria.[10 (link)]
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5

Coronary Artery Calcium Scoring by CT

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All patients with heart rates > 70 bpm received oral β-blocker therapy, with 50 or 100 mg of metoprolol tartrate (AstraZeneca, Zoetermeer, the Netherlands) after stress testing to achieve a heart rate < 70 bpm for the CAC scan. A non-enhanced CT scan (High Definition CT XT; GE Healthcare) during breath-hold at end expiration to calculate the total CAC score was acquired with ECG triggering at 75% of the R-R interval and with the following scanning parameters: 40 or 48 sections and 2.5-mm section thickness; gantry rotation time, 330 ms; tube voltage, 120 kV; and a tube current of 125 mA. If patients were not able to hold their breath, a free breathing CT was acquired. Post processing was conducted at a dedicated workstation using Smartscore software (GE Healthcare). The CAC score was calculated using the standard Agatston criteria [5 (link)].
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6

Doxorubicin and Metoprolol Tartrate Protocol

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Doxorubicin (APExBIO Company, Lot No.: A39662 337,769); Metoprolol tartrate (AstraZeneca Pharmaceutical (China) Co. Ltd., Lot No.: 0902066); 4% paraformaldehyde (Changsha Weisher Biotechnology Co. Ltd., Lot No.: WB03004A); DNA extraction kit (E.Z.N.A.® Soil DNA Kit, Omega Bio-Tek, USA); AxyPrep DNA Gel Extraction Kit (Axygen biosciences, axygen, USA); MiSeq PE300 (Illumina, USA); Magnetic frame (China Bioengineering (Shanghai) Co. Ltd); Sequencer (Illumina Miseq, Illumina, USA); PCR instrument (ABI GeneAmp® 9700, ABI, USA); Electrophoresis instrument (DYY-6C, Beijing Liuyi Instrument Factory, China); Database building kit (NEXTFLEX® Rapid DNA-Seq Kit, Bioo Scientific, USA); Agarose (biowest Agarose, biowest, Spain); FastPfu Polymerase (FastPfu Polymerase, TransGen, China); Sequencing kit (MiSeq Reagent Kit v3, Illumina, USA).
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7

Evaluating Enhancer Mechanisms on Model Drugs

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Four model compounds were selected: Atenolol, Enalaprilat, ketoprofen, and metoprolol. Biopharmaceutical classification (BCS) and some physicochemical properties for the four drugs are summarized in Table 1. Four PEs with different mechanisms of action were selected: SDS (anionic surfactant), sodium caprate (fatty acid), chitosan (polysaccharide), and EDTA (chelating agent). Atenolol and metoprolol tartrate were provided by AstraZeneca AB (Mölndal, Sweden). Enalaprilat, ketoprofen, sodium caprate, SDS, bovine albumin (A2153), EDTA, and inactin (thiobutabarbital) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Sodium phosphate dibasic dihydrate (Na2HPO4·2H2O), potassium dihydrogen phosphate (KH2PO4), sodium hydroxide (NaOH), and sodium chloride (NaCl) were purchased from Merck KGaA (Darmstadt, Germany). 51Cr-EDTA was purchased from PerkinElmer Life Sciences (Boston, MA, USA). Chitosan hydrochloride (molecular mass 40-300 kDa, degree of acetylation 8.8%) was purchased from Kraeber and Co GmbH (Ellerbek, Germany). Parecoxib (dynastat) was obtained from Apoteket AB, Uppsala, Sweden.
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8

Metoprolol Tartrate Quantification Protocol

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Metoprolol tartrate was obtained from AstraZeneca Pharmaceutical Co., Ltd. (Jiangsu, China). Barium chloride was obtained from Maoye Chemical Reagent Co., Ltd. (Chongqing, China). LC grade acetonitrile was purchased from Merck (Merck, Darmstadt, Germany). Isopropanol, formic acid and metabolite standards were purchased from Sigma-Aldrich (Sigma-Aldrich, St Louis, MO, USA). Purified water (18.2 MΩ) was prepared from a Mill-Q purification system (Millipore Corp., MA, USA).
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9

Yiqi Huoxue Decoction Preparation Protocol

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Trizol was purchased from Invitrogen (CA, USA). Reverse transcription system (A3500) was purchased from Promega (WI, USA). The ab21685-100 antibody against GRP78 and the antibody against caspase-12 (Ab62484-100) were purchased from Abcam (Cambridge, UK). Antibody against GAPDH (Cs 2118) was provided from Cell Signaling Technology (Boston, US). The terminal deoxynucleotidyltransferase-mediated dUTP Nick End Labeling (TUNEL) kit was obtained from Wuhan Boster Biological Technology Ltd. (Wuhan, China). Other chemicals and reagents were of analytical grade.
Preparation of Yiqi Huoxue Decoction. Yiqi Huoxue Decoction consists of Astragalus, Angelica, and Ginseng in a 13 : 6 : 10 ratios. Slices of the herbs were provided by pharmaceutical preparation section, Dongzhimen hospital, Beijing, China. The medicinal herbs were extracted twice. Based on the ratios, Slices of those herbs were first boiled together in 6x volume of water for 0.5 h, and then the residue from first extraction was boiled in 8x volume of water for 25 min. Finally, the filtered solutions were combined and concentrated into the resulting aqueous extracts containing 1.2 g/mL raw herbs. Metoprolol Tartrate (MT) was purchased from AstraZeneca Company (Jiangsu, China).
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10

Coronary Artery Calcium Scoring Protocol

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All patients with heart rates >70 bpm received oral β-blocker therapy, with 50 or 100 mg of metoprolol tartrate (AstraZeneca, Zoetermeer, the Netherlands) after stress testing to achieve a heart rate <70 bpm for the CAC scan.
A nonenhanced CT scan (LightSpeed VCT XT; GE Healthcare) during breath-hold at end expiration to calculate the total CAC score was acquired with ECG triggering at 75% of the R-R interval and the following scanning parameters: 40 or 48 sections and 2.5-mm section thickness; gantry rotation time, 330 ms; tube voltage, 120 kV; and a tube current of 125 mA. If patients were not able to hold their breath, a free breathing CT was acquired. Postprocessing was conducted at a dedicated workstation using Smartscore software (GE Healthcare). The CAC score was calculated using the standard Agatston criteria. 12
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