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

OBJECTIVE: To investigate the diagnostic validity of coronary computed tomography angiography (cCTA) in vasospastic angina (VA) and factors associated with discrepant results between invasive coronary angiography with the ergonovine provocation test (iCAG-EPT) and cCTA. MATERIALS AND METHODS: Of the 1397 patients diagnosed with VA from 2006 to 2016, 33 patients (75 lesions) with available cCTA data from within 6 months before iCAG-EPT were included. The severity of spasm (% diameter stenosis [%DS]) on iCAG-EPT and cCTA was assessed, and the difference in %DS (Δ%DS) was calculated. Δ%DS was compared after classifying the lesions according to pre-cCTA-administered sublingual nitroglycerin (SL-NG) or beta-blockers. The lesions were further categorized with %DS ≥ 50% on iCAG-EPT or cCTA defined as a significant spasm, and the diagnostic performance of cCTA on identifying significant spasm relative to iCAG-EPT was assessed. RESULTS: Compared to lesions without SL-NG treatment, those with SL-NG treatment showed a higher Δ%DS (39.2% vs. 22.1%, p = 0.002). However, there was no difference in Δ%DS with or without beta-blocker treatment (35.1% vs. 32.6%, p = 0.643). The significant difference in Δ%DS associated with SL-NG was more prominent in patients who were aged < 60 years, were male, had body mass index < 25 kg/m2, and had no history of hypertension, diabetes, or dyslipidemia. Based on iCAG-EPT as the reference, the per-lesion-based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of cCTA for VA diagnosis were 7.5%, 94.0%, 60.0%, 47.1%, and 48.0%, respectively. CONCLUSION: For patients with clinically suspected VA, confirmation with iCAG-EPT needs to be considered without completely excluding the diagnosis of VA simply based on cCTA results, although further prospective studies are required for confirmation.
Angina Pectoris, Variant ; Angiography ; Body Mass Index ; Constriction, Pathologic ; Coronary Angiography ; Diagnosis ; Dyslipidemias ; Ergonovine ; Humans ; Hypertension ; Male ; Nitroglycerin ; Prospective Studies ; Sensitivity and Specificity ; Spasm

OBJECTIVES: Medically compromised patients often fear required dental surgical procedures that can increase the risk of medical emergency when combined with reduced tolerance for stress. A stress reduction protocol (SRP) helps doctors minimize treatment-related stress and improves patient management with minimum complications. Diabetes and co-morbid hypertension carry 4-fold risk of aggravation of cardiovascular emergencies and 7.2-fold risk of mortality. Diabetic neuropathy can result in difficult diagnosis of myocardial infarction and reduces chances of surviving a myocardial infarction compared with a non-diabetic person. The aim of the study was to assess the feasibility of a protocol for management of patients having both diabetes and hypertension who required minor oral surgery to minimize the rate of cardiovascular emergencies. MATERIALS AND METHODS: A prospective study was conducted in 140 patients having both diabetes and hypertension who required minor oral surgical procedures. A systematic approachable protocol was designed for management of such patients. RESULTS: Among 140 patients, 6 patients (4.3%) had cardiovascular complications, while 3 patients (1 with syncope and 2 with hypertension) did not require any intervention other than observation. Two patients were managed with aspirin and nitroglycerin, and 1 patient had possible myocardial infarction (overall incidence 0.7%) with chest pain, S-T segment elevation on electrocardiogram, and troponin level of 0.60 ng/mL. CONCLUSION: The proposed protocol helps to improve management of patients having both diabetes and hypertension. We recommend that patients with uncontrolled diabetes and uncontrolled hypertension and/or patients having history of cardiovascular complication should be treated in a medical facility with a readily available cardiology unit. This facilitates prompt response to emergency and instant implementation of treatment, helping to reduce morbidity and mortality.
Aspirin ; Cardiology ; Chest Pain ; Diabetic Neuropathies ; Diagnosis ; Electrocardiography ; Emergencies ; Humans ; Hypertension ; Incidence ; Mortality ; Myocardial Infarction ; Nitroglycerin ; Oral Surgical Procedures ; Prospective Studies ; Surgery, Oral ; Syncope ; Troponin

A 57-year-old woman scheduled for cochlear implant removal exhibited preoperative electrocardiographic findings of early repolarization (ER). Four episodes of transient ST segment elevations during surgery raised suspicion for vasospastic angina (VA). In the post-anesthetic care unit, the patient complained of chest discomfort and received sublingual nitroglycerin with uncertain effect. The patient refused to proceed with postoperative invasive coronary angiography, resulting in inconclusive diagnosis. Intraoperative circumstances limit the diagnosis of VA, which emphasizes the need for further testing to confirm the diagnosis. When VA is suspected in patients with underlying ER, it is reasonable to consider invasive examination to establish the diagnosis and prevent recurrence of VA. If ST changes are observed during surgery in patients with preoperative ER, careful monitoring is recommended. Due to general anesthesia, the absence of patient symptoms limits the definitive diagnosis of those with suspected VA. Therefore, additional postoperative surveillance is recommended.
Anesthesia, General ; Cochlear Implants ; Coronary Angiography ; Diagnosis ; Electrocardiography ; Female ; Head ; Humans ; Middle Aged ; Neck ; Nitroglycerin ; Recurrence ; Thorax

Variant angina pectoris (VAP) is a special type of unstable angina with coronary artery spasm as the main pathogenesis, characterized by resting chest pain, and transient ST segment dynamic changes. The development of acute myocardial infarction is not uncommon. We report a case of a 49-year-old female patient diagnosed with VAP at 2 years before who suddenly suffered severe chest pain. Troponin-I was elevated. Immediate coronary angiography showed near-total occlusion in the proximal left anterior descending artery, which was not fully dilated despite use of intracoronary nitroglycerin. Intravascular ultrasound showed focal significant stenosis with a large amount of plaque at the site of spasm and the lesion was successfully treated with drug-eluting stent placement. Intravascular imaging may be instrumental in high-risk patients with VAP who suffer recurrent chest pain despite intensive anti-spasm medications.
Angina Pectoris, Variant ; Angina, Unstable ; Arteries ; Atherosclerosis* ; Chest Pain ; Constriction, Pathologic ; Coronary Angiography ; Coronary Vessels ; Drug-Eluting Stents ; Female ; Humans ; Middle Aged ; Myocardial Infarction* ; Nitroglycerin ; Spasm* ; Troponin I ; Ultrasonics ; Ultrasonography

PURPOSE: Coronary artery spasm (CAS) and diabetes mellitus (DM) are implicated in endothelial dysfunction, and insulin resistance (IR) is a major etiological cause of type 2 DM. However, the association between CAS and IR in non-diabetic individuals has not been elucidated. The aim of the present study was to evaluate the impact of IR on CAS in patients without DM. MATERIALS AND METHODS: A total of 330 eligible patients without DM and coronary artery disease who underwent acetylcholine (Ach) provocation test were enrolled in this study. Inclusion criteria included both hemoglobin A1c < 6.0% and fasting glucose level < 110 mg/dL without type 2 DM. Patients were divided into quartile groups according the level of homeostasis model assessment of insulin resistance (HOMA-IR): 1Q (n=82; HOMA-IR < 1.35), 2Q (n=82; 1.35≤HOMA-IR < 1.93), 3Q (n=83; 1.93≤HOMA-IR < 2.73), and 4Q (n=83; HOMA-IR≥2.73). RESULTS: In the present study, the higher HOMA-IR group (3Q and 4Q) was older and had higher body mass index, fasting blood glucose, serum insulin, hemoglobin A1c, total cholesterol, and triglyceride levels than the lower HOMA-IR group (1Q). Also, poor IR (3Q and 4Q) was considerably associated with frequent CAS. Compared with Q1, the hazard ratios for Q3 and Q4 were 3.55 (95% CI: 1.79–7.03, p < 0.001) and 2.12 (95% CI: 1.07–4.21, p=0.031), respectively, after adjustment of baseline risk confounders. Also, diffuse spasm and accompanying chest pain during Ach test were more strongly associated with IR patients with CAS. CONCLUSION: HOMA-IR was significantly negatively correlated with reference diameter measured after nitroglycerin and significantly positively correlated with diffuse spasm and chest pain.
Acetylcholine ; Blood Glucose ; Body Mass Index ; Chest Pain ; Cholesterol ; Coronary Artery Disease ; Coronary Vessels* ; Diabetes Mellitus ; Fasting ; Glucose ; Homeostasis ; Humans ; Insulin Resistance* ; Insulin* ; Nitroglycerin ; Spasm* ; Triglycerides

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

PURPOSE: In Korea, the EMS system is a municipal governmental fire-based system. Since 2012, an EMS medical director has been appointed in all fire stations by legislation. This study examined the direct medical oversight (DMO) clinically in a Korean metropolitan city. METHODS: This is a descriptive analysis of the fire-based centralized DMO in a metropolitan city. The current status of the ambulance crew of a fire station including certification, EMS experience, the number of requested DMO, and the statistics of DMO, and the DMO physicians of a fire department dispatch center, was studied. The ambulance run sheets of a fire station were reviewed to survey the assessment and intervention of ambulance-receiving DMO. RESULTS: Although it is increasing every year, the ratio of ambulance runs receiving DMO was 2.5–11.1% in a fire station. The fire station has 45 ambulance crew, half of which were level 1 emergency medical technicians and registered nurses. In a fire department dispatch center, most (70%) of the DMO physicians were emergency physicians. The ratio of prehospital assessment, including consciousness (100%), full vital sign (78.8–91.2%), oxygen saturation (86.5–100%), blood sugar test (31.3–94.4%), and ECG (16.7–48.5%), was higher than the ratio of prehospital intervention, including advanced airway (1.9–21.15), bag mask ventilation (3.0–63.2%), IV dextrose water (55.6%), nitroglycerin subligual (42.9%), cervical immobilization (57.7%), and wound dressing (53.85) in an ambulance run receiving DMO in a fire station. CONCLUSION: The ratio of patients transported by ambulance receiving DMO is still low in a metropolitan city. The DMO should be strengthened to improve the patient safety and quality of EMS in Korea.
Ambulances ; Bandages ; Blood Glucose ; Certification ; Consciousness ; Electrocardiography ; Emergencies ; Emergency Medical Service Communication Systems ; Emergency Medical Services ; Emergency Medical Technicians ; Fires ; Glucose ; Humans ; Immobilization ; Korea ; Local Government ; Masks ; Nitroglycerin ; Nurses ; Oxygen ; Patient Safety ; Physician Executives ; Ventilation ; Vital Signs ; Water ; Wounds and Injuries

We report successful resuscitation of a patient after cardiac arrest on postoperative day 4 after coronary artery bypass grafting (CABG). The patient underwent proximal right coronary artery stent insertion 1 year preceding his CABG, and in-stent restenosis of the stent was found on coronary angiography (CAG). CABG was planned. The patient was treated with a nitroglycerin (NTG) for chest pain, and in the holding area of the operating theater, his chest pain resumed during brief cessation of the NTG while changing the syringe pump. Intraoperatively, normal flow was confirmed at the graft site with flowmetry, while the patient received a NTG infusion. On postoperative day 4, the patient developed chest pain and a subsequent cardiac arrest. He was resuscitated with chest compressions alone, and emergent CAG was performed. It showed coronary artery spasm of the left anterior descending coronary artery, confirmed by provocation testing. The patient was discharged with symptoms well controlled on oral medications.
Chest Pain ; Coronary Angiography ; Coronary Artery Bypass* ; Coronary Vessels* ; Heart Arrest* ; Humans ; Nitroglycerin ; Percutaneous Coronary Intervention ; Resuscitation ; Rheology ; Spasm* ; Stents ; Syringes ; Thorax ; Transplants

Radiofrequency ablation (RFA) is a minimally invasive procedure that has been considered as a relatively safe treatment for patients with small hepatocellular carcinoma (HCC). However, RFA has been shown to be associated with complications including mechanical and thermal damage. A 74-year-old man with hepatitis C virus-associated HCC was admitted to our hospital. Abdominal computed tomography revealed two lobulated-HCC in segments 4 and 5. He had no medical history of hypertension and cardiac disease. During RFA, blood pressure was elevated to 200/140 mmHg. There was no evidence of pulmonary embolism, aortic dissection, or ischemic heart disease. Laboratory findings for catecholamine surge were all within normal limits. After continuous intravenous nitroglycerin and oral beta-blocker treatment, patient's blood pressure gradually decreased and back within the normal range. Hypertensive crisis after RFA treatment for HCC is rare. Most reported cases of hypertensive crisis during RFA were related to adrenal gland injury with a release of catecholamine. In our case, the site of HCC was not close to the adrenal gland, and there was no evidence of catecholamine surge. Herein, we report a very rare case of hypertensive crisis without a surge in adrenal hormones after RFA treatment for HCC.
Adrenal Glands ; Aged ; Blood Pressure ; Carcinoma, Hepatocellular* ; Catheter Ablation* ; Heart Diseases ; Hepatitis C ; Humans ; Hypertension ; Myocardial Ischemia ; Nitroglycerin ; Pulmonary Embolism ; Reference Values