A sensitive and specific ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was deve-loped for analysis of rutaecarpine(Ru), evodiamine(Ev), rutaevine(Rv), limonin(Li), ginsendside Rb_1(Rb_1), ginsendside Re(Re) in rat plasma and brain tissues of nitroglycerin-induced migraine rats. Male healthy Sprague-Dawley(SD) rats were orally given multiple dose of optimized(OS) and un-optimized Wuzhuyu Decoction(UNOS), and their blood samples and brainstem were collected at different time points after injection of nitroglycerin(10 mg·kg~(-1)) into the frontal region. The drug concentrations of the 6 analytes in plasma and brainstem were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma were calculated by using Phoenix WinNolin 5.2.1 software. The methodological test showed that all of analytes in both plasma and brainstem homogenate exhibited a good linearity within the concentration range(r>0.994 7). The intra-day and inter-day accuracy, precision, matrix effect, stability of the investigated components meet the requirements for biopharmaceutical analysis. The developed method was successfully applied in pharmacokinetic studies on abovementioned ingredients in rat plasma and brain stem. The plasma pharmacokinetic parameters of active ingredients in two different Wuzhuyu Decoction group were compared, it was found that Rb_1 had higher t_(1/2), T_(max), C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. Meanwhile, Ev had higher t_(1/2) and T_(max) but lower C_(max), AUC_(0-24 h) and AUC_(0-∞), Ru has higher t_(1/2 )but lower C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. The brain tissue distribution of each component were compared between the two groups, the component with higher content in OS, such as Ru at 30 min and 2 h after administration, Ev at 30 min, Rb_1 at 30 min and Rb_1 at 2 h after administration have lower brain tissue distribution than those in UNOS group, while the component with higher content in UNOS, such as Rv at 30 min, 2 h and 12 h after administration had higher brain tissue distribution than those in OS group.
Administration, Oral ; Animals ; Brain/drug effects* ; Brain Chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Migraine Disorders/drug therapy* ; Nitroglycerin ; Plasma/chemistry* ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry

PURPOSE: Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial. MATERIALS AND METHODS: Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared. RESULTS: Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar. CONCLUSION: Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.
Acute Disease ; Aged ; Antihypertensive Agents/*administration & dosage ; Blood Pressure/drug effects ; Cause of Death ; Female ; Heart Failure/*drug therapy/physiopathology ; Heart Rate/drug effects/physiology ; Hemodynamics ; Humans ; Hypertension/*drug therapy/physiopathology ; Injections, Intravenous ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Nitroglycerin/administration & dosage ; Peptide Fragments/blood ; Piperazines/*administration & dosage ; Ventricular Function, Left/drug effects/physiology

Although alpha2-adrenoceptor agonists are widely used as postoperative sedatives in adults, the postoperative effects in pediatric patients with secondary pulmonary arterial hypertension (PAH) due to congenital heart disease are not well known. We experienced a case of successful ventilator weaning with continuous intravenous administration of dexmedetomidine (DEX) after surgical correction in a 46-month-old child with congenital ventricular septal defect (VSD) with severe PAH. She underwent VSD closure on cardiopulmonary bypass (CPB). After successful weaning from the CPB, hemodynamics and oxygenation were stabilized on DEX and nitroglycerin in the intensive care unit. The patient was successfully weaned from the ventilator 46 hours after surgery. The transthoracic echocardiogram two weeks after surgery showed a closed VSD with no residual shunt and trivial tricuspid regurgitation (Vmax = 2.5 m/sec) without PAH.
Administration, Intravenous ; Adult ; Cardiopulmonary Bypass ; Child* ; Child, Preschool ; Dexmedetomidine* ; Heart Defects, Congenital ; Heart Septal Defects, Ventricular* ; Hemodynamics ; Humans ; Hypertension* ; Hypnotics and Sedatives ; Intensive Care Units ; Nitroglycerin ; Oxygen ; Tricuspid Valve Insufficiency ; Ventilator Weaning ; Ventilators, Mechanical ; Weaning

Although alpha2-adrenoceptor agonists are widely used as postoperative sedatives in adults, the postoperative effects in pediatric patients with secondary pulmonary arterial hypertension (PAH) due to congenital heart disease are not well known. We experienced a case of successful ventilator weaning with continuous intravenous administration of dexmedetomidine (DEX) after surgical correction in a 46-month-old child with congenital ventricular septal defect (VSD) with severe PAH. She underwent VSD closure on cardiopulmonary bypass (CPB). After successful weaning from the CPB, hemodynamics and oxygenation were stabilized on DEX and nitroglycerin in the intensive care unit. The patient was successfully weaned from the ventilator 46 hours after surgery. The transthoracic echocardiogram two weeks after surgery showed a closed VSD with no residual shunt and trivial tricuspid regurgitation (Vmax = 2.5 m/sec) without PAH.
Administration, Intravenous ; Adult ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Dexmedetomidine ; Heart Defects, Congenital ; Heart Septal Defects, Ventricular ; Hemodynamics ; Humans ; Hypertension ; Hypnotics and Sedatives ; Intensive Care Units ; Nitroglycerin ; Oxygen ; Tricuspid Valve Insufficiency ; Ventilator Weaning ; Ventilators, Mechanical ; Weaning

The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 μg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.
Administration, Intranasal ; Administration, Oral ; Animals ; Bradykinin ; Female ; Hyperalgesia ; chemically induced ; prevention & control ; Male ; Migraine Disorders ; chemically induced ; prevention & control ; Models, Animal ; Nitroglycerin ; Nociception ; drug effects ; Plant Leaves ; chemistry ; Pre-Exposure Prophylaxis ; Rats ; Rats, Wistar ; Reaction Time ; Receptors, Serotonin, 5-HT1 ; drug effects ; Serotonin 5-HT1 Receptor Antagonists ; metabolism ; Tail ; physiology ; Triterpenes ; administration & dosage ; pharmacology

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use

Cardiotoxicity associated with 5-fluorouracil (FU) is an uncommon, but potentially lethal, condition. The case of an 83-year-old man with colon cancer who developed chest pain during 5-FU infusion is presented. The electrocardiogram (ECG) showed pronounced ST elevation in the lateral leads, and the chest pain was resolved after infusion of nitroglycerin. A coronary angiogram (CAG) revealed that the patient had significant atherosclerosis in the proximal left circumflex artery. Coronary artery spasm with fixed stenosis was considered, and a drug-eluting stent was implanted. After 8 hours, the patient complained of recurring chest pain, paralleled by ST elevation on the ECG. The chest pain subsided after administration of intravenous nitroglycerin followed by sublingual nifedipine. Repeated CAG showed patency of the previous stent. This case supports the vasospastic hypothesis of 5-FU cardiac toxicity, indicating that a calcium channel blocker may be effective in the prevention or treatment of 5-FU cardiotoxicity.
Aged, 80 and over ; Angina Pectoris/chemically induced ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects ; Calcium Channel Blockers/administration & dosage ; Colonic Neoplasms/*drug therapy ; Coronary Angiography ; Coronary Vasospasm/*chemically induced/diagnosis/therapy ; Drug-Eluting Stents ; Electrocardiography ; Fluorouracil/administration & dosage/*adverse effects ; Humans ; Leucovorin/administration & dosage/adverse effects ; Male ; Nifedipine/administration & dosage ; Nitroglycerin/administration & dosage ; Organoplatinum Compounds/administration & dosage/adverse effects ; Percutaneous Coronary Intervention/instrumentation ; Recurrence ; Severity of Illness Index ; Treatment Outcome ; Vasodilator Agents/administration & dosage

BACKGROUND: Smoking is one of well known environmental factors causing endothelial dysfunction and plays important role in the atherosclerosis. We investigated the effect of cilostazol could improve the endothelial dysfunction in smokers with the measurement of flow-mediated dilatation (FMD). METHODS: We enrolled 10 normal healthy male persons and 20 male smokers without any known cardiovascular diseases. After measurement of baseline FMD, the participants were medicated with oral cilostazol 100 mg bid for two weeks. We checked the follow up FMD after two weeks and compared these values between two groups. RESULTS: There was no statistical difference of baseline characteristics including age, body mass index, serum cholesterol profiles, serum glucose and high sensitive C-reactive protein between two groups. However, the control group showed significantly higher baseline endothelium-dependent dilatation (EDD) after reactive hyperemia (12.0 +/- 4.5% in the control group vs. 8.0 +/- 2.1% in the smoker group, p = 0.001). However, endothelium-independent dilatation (EID) after sublingual administration of nitroglycerin was similar between the two groups (13.6 +/- 4.5% in the control group vs. 11.9 +/- 4.9% in the smoker group, p = 0.681). Two of the smoker group were dropped out due to severe headache. After two weeks of cilostazol therapy, follow-up EDD were significantly increased in two groups (12.0 +/- 4.5% to 16.1 +/- 3.7%, p = 0.034 in the control group and 8.0 +/- 2.1% to 12.2 +/- 5.1%, p = 0.003 in the smoker group, respectively). However, follow up EID value was not significantly increased compared with baseline value in both groups (13.6 +/- 4.5% to 16.1 +/- 3.7%, p = 0.182 in the control group and 11.9 +/- 4.9% to 13.7 +/- 4.3%, p = 0.430 in the smoker group, respectively). CONCLUSION: Oral cilostazol treatment significantly increased the vasodilatory response to reactive hyperemia in two groups. It can be used to improve endothelial function in the patients with endothelial dysfunction caused by cigarette smoking.
Administration, Sublingual ; Atherosclerosis ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Cholesterol ; Dilatation ; Follow-Up Studies ; Glucose ; Headache ; Humans ; Hyperemia ; Male ; Nitroglycerin ; Smoke ; Smoking ; Tetrazoles

OBJECTIVETo observe the differences of therapeutic effect of acupoint pressing, Nitroglycerin and Suxiaojiuxin pill on angina pectoris (AP) due to coronary heart disease (CHD).

METHODSOne hundred and six ty-eight patients with AP due to CHD were randomly divided into an acupoint pressing group (n = 58), a Nitro glycerin group (n = 56) and a Suxiaojiuxin pill group (n = 54) and were treated with acupoint pressing at Danzhong (CV 17) for 5-10 minutes, sublingual administration of Nitroglycerin and sublingual administration of Suxiaojiuxin pill, respectively. Symptoms, improvements in ECG, the time of producing effectiveness and adverse effects in all the groups were observed.

RESULTSThe total effective rate and the effective rate of ECG were 93.1% (54/58) and 86.2% (50/58) in the acupoint pressing group respectively, 92.9% (52/56) and 85.7% (48/56) in the Nitroglycerin group, and 87.0% (47/54) and 75.9% (41/54) in the Suxiaojiuxin pill group, with no significant differences among the three groups (all P > 0.05). The average time of producing effectiveness was (1.67 +/- 2.45) min in the acupoint pressing group which was shorter than (2.89 +/- 2.64) min in the Nitroglycerin group and (3.75 +/- 2.99) min in the Suxiaojiuxin pill group (P < 0.05, P < 0.001). During the treatment, there were no adverse effects in the acupoint pressing group, which less than 19 cases in the Nitroglycerin group and 12 cases in the Suxiaojiuxin pill group (both P < 0.05).

CONCLUSIONAcupoint pressing can significantly improve symptoms of AP patients with a similar therapeutic effect to Nitroglycerin and Suxiaojiuxin pill, but it has more rapid therapeutic effect without adverse effects.

Acupressure ; Acupuncture Points ; Adult ; Aged ; Angina Pectoris ; drug therapy ; etiology ; therapy ; Coronary Disease ; complications ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin ; administration & dosage ; Vasodilator Agents ; administration & dosage