Hemodynamic effects of nitroglycerin ointment in emergency department patients.

PubMed

Mumma, Bryn E; Dhingra, Kapil R; Kurlinkus, Charley; Diercks, Deborah B

2014-08-01

Nitroglycerin ointment is commonly used in the treatment of emergency department (ED) patients with suspected acute heart failure (AHF) or suspected acute coronary syndrome (ACS), but its hemodynamic effects in this population are not well described. Our objective was to assess the effect of nitroglycerin ointment on mean arterial pressure (MAP) and systemic vascular resistance (SVR) in ED patients receiving nitroglycerin. We hypothesized that nitroglycerin ointment would result in a reduction of MAP and SVR in the acute treatment of patients. We conducted a prospective, observational pilot study in a convenience sample of adult patients from a single ED who were treated with nitroglycerin ointment. Impedance cardiography was used to measure MAP, SVR, cardiac output (CO), stroke volume (SV), and thoracic fluid content (TFC) at baseline and at 30, 60, and 120 min after application of nitroglycerin ointment. Mixed effects regression models with random slope and random intercept were used to analyze changes in hemodynamic parameters from baseline to 30, 60, and 120 min after adjusting for age, sex, and final ED diagnosis of AHF. Sixty-four subjects with mean age of 55 years (interquartile range, 48-67 years) were enrolled; 59% were male. In the adjusted analysis, MAP and TFC decreased after application of nitroglycerin ointment (p=0.001 and p=0.043, respectively). Cardiac index, CO, SVR, and SV showed no change (p=0.113, p=0.085, p=0.570, and p=0.076, respectively) over time. Among ED patients who are treated with nitroglycerin ointment, MAP and TFC decrease over time. However, other hemodynamic parameters do not change after application of nitroglycerin ointment in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Continuous transdermal nitroglycerin therapy for menopausal hot flashes: a single-arm, dose-escalation trial.

PubMed

Huang, Alison J; Cummings, Steven R; Schembri, Michael; Vittinghoff, Eric; Ganz, Peter; Grady, Deborah

2016-03-01

To describe the efficacy and tolerability of continuous nitroglycerin for treatment of hot flashes. Perimenopausal and postmenopausal women reporting at least seven hot flashes per day were recruited into a single-arm, dose-escalation trial of continuous transdermal nitroglycerin. Participants were started on a generic 0.1 mg/hour nitroglycerin patch applied daily without patch-free periods. During 4 weeks, participants escalated dosage weekly to 0.2, 0.4, or 0.6 mg/hour as tolerated, then discontinued nitroglycerin during the final week. Changes in hot flash frequency and severity were assessed using symptom diaries. Paired t tests examined change in outcomes between baseline and maximal-dose therapy and after discontinuation of nitroglycerin. Of the 19 participants, mean age was 51.4 (±4.3) years. Women reported an average 10.6 (±3.0) hot flashes and 7.1 (±3.8) moderate-to-severe hot flashes per day at baseline. Eleven women escalated to 0.6 mg/hour, three to 0.4 mg/hour, two to 0.2 mg/hour, and one remained on 0.1 mg/hour nitroglycerin. Two discontinued nitroglycerin before the first outcomes assessment. Among the remaining 17 women, the average daily frequency of hot flashes decreased by 54% and the average frequency of moderate-to-severe hot flashes decreased by 69% from baseline to maximum-dose therapy (P < 0.001 for both). After discontinuing nitroglycerin, participants reported an average 23% increase in frequency of any hot flashes (P = 0.041) and 96% increase in moderate-to-severe hot flashes (P < 0.001). Continuous nitroglycerin may substantially and reversibly decrease hot flash frequency and severity. If confirmed in a randomized blinded trial, it may offer a novel nonhormonal hot flash treatment.

Continuous Transdermal Nitroglycerin Therapy for Menopausal Hot Flashes: A Single-Arm Dose-Escalation Trial

PubMed Central

Huang, Alison J.; Cummings, Steven R.; Schembri, Michael; Vittinghoff, Eric; Ganz, Peter; Grady, Deborah

2015-01-01

Objective To describe the efficacy and tolerability of continuous nitroglycerin for treatment of hot flashes. Methods Peri- and postmenopausal women reporting at least 7 hot flashes per day were recruited into a single-arm, dose-escalation trial of continuous transdermal nitroglycerin. Participants were started on a generic 0.1 mg/hr nitroglycerin patch applied daily without patch-free periods. Over four weeks, participants escalated dosage weekly to 0.2, 0.4, or 0.6 mg/hr as tolerated, then discontinued nitroglycerin during the final week. Changes in hot flash frequency and severity were assessed using symptom diaries. Paired t-tests examined change in outcomes between baseline and maximal-dose therapy as well as after discontinuation of nitroglycerin. Results Of the 19 participants, mean age was 51.4 (±4.3) years. Women reported an average 10.6 (±3.0) hot flashes and 7.1 (±3.8) moderate-to-severe hot flashes per day at baseline. Eleven women escalated to 0.6 mg/hr, three to 0.4 mg/hr, two to 0.2 mg/hr, and one remained on 0.1 mg/hr nitroglycerin. Two discontinued nitroglycerin before the first outcomes assessment. Among the remaining 17 women, the average daily frequency of hot flashes decreased by 54% and the average frequency of moderate-to-severe hot flashes decreased by 69% from baseline to maximum-dose therapy (P<0.001 for both). After discontinuing nitroglycerin, participants reported an average 23% increase in frequency of any hot flashes (P=0.041) and 96% increase in moderate-to-severe hot flashes (P<0.001). Conclusions Continuous nitroglycerin may substantially and reversibly decrease hot flash frequency and severity. If confirmed in a randomized blinded trial, it may offer a novel non-hormonal hot flash treatment. PMID:26263283

Hemodynamic Effects of Nitroglycerin Ointment in Emergency Department Patients

PubMed Central

Mumma, Bryn E.; Dhingra, Kapil R.; Kurlinkus, Charley; Diercks, Deborah B.

2014-01-01

Background Nitroglycerin ointment is commonly used in the treatment of emergency department (ED) patients with suspected acute heart failure (AHF) or suspected acute coronary syndrome (ACS), but its hemodynamic effects in this population are not well described. Objectives Our objective was to assess effect of nitroglycerin ointment on mean arterial pressure (MAP) and systemic vascular resistance (SVR) in ED patients receiving nitroglycerin. We hypothesized that nitroglycerin ointment would result in a reduction of MAP and SVR in the acute treatment of patients. Methods We conducted a prospective, observational pilot study in a convenience sample of adult patients from a single ED who were treated with nitroglycerin ointment. Impedance cardiography was used to measure MAP, SVR, cardiac output (CO), stroke volume (SV), and thoracic fluid content (TFC) at baseline and at 30, 60, and 120 minutes following application of nitroglycerin ointment. Mixed effects regression models with random slope and random intercept were used to analyze changes in hemodynamic parameters from baseline to 30, 60, and 120 minutes after adjusting for age, sex, and final ED diagnosis of AHF. Results Sixty-four subjects with mean age 55 years (IQR 48-67) were enrolled; 59% were male. In the adjusted analysis, MAP and TFC decreased following application of nitroglycerin ointment (p=0.001 and p=0.043, respectively). CI, CO, SVR, and SV showed no change (p=0.113, p=0.085, p=0.570, and p=0.076, respectively) over time. Conclusions Among ED patients who are treated with nitroglycerin ointment, MAP and TFC decrease over time. However, other hemodynamic parameters do not change following application of nitroglycerin ointment in these patients. PMID:24698507

Influence of Nitroglycerin on Coronary Artery CT Imaging in Cardiovascular Diseases.

PubMed

Zhang, PeiYing

2015-06-01

This study was designed to observe the influence of nitroglycerin on the quality of coronary artery imaging when CT is used for coronary heart disease. Data of 150 cardiology inpatients were collected from Department of Cardiology of our hospital from November 2013 to August 2014 for this study. All the subjects were diagnosed with multislice CT and coronary angiography after admission. The patients were then divided into two groups, the nitroglycerin group of 75 cases who took nitroglycerin and the control group of 75 cases who took no nitroglycerin. A total of 320 mixed plaques (pathological characteristics of calcified ingredients and non-calcified ingredients), including 290 calcified mixed plaques of type I, (mainly with calcified plaques and purely calcified plaques), and 30 non-calcified plaques of type II, (mainly with non-calcified ingredients or pure non-calcified plaques) were scanned. CT coronary angiography showed that the detection rate of type I plaque was 65.5 % in control group and 34.8 % in nitroglycerin group, whereas the detection rate of type II plaque was 30 % in control group and 70 % in nitroglycerin group. The difference for both type I and type II was statistically significant (p < 0.05). In Comparison with control group, the increase in diameter of 1-13 vascular segments in nitroglycerin group was statistically significant (p < 0.05). Taking nitroglycerin can improve the display resolution of coronary angiography, and shows better display for type I than type II plaques.

Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography: a Systematic Review.

PubMed

Takx, Richard A P; Suchá, Dominika; Park, Jakob; Leiner, Tim; Hoffmann, Udo

2015-12-01

To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Sublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes. • Sublingual nitroglycerin administration results in significant coronary artery dilatation. • Nitroglycerin increases the number of evaluable coronary branches. • Image quality is improved the most in smaller coronary branches. • Nitroglycerin increases the diagnostic accuracy of coronary CT angiography. • Most side effects are mild and do not require medical intervention.

Nitroglycerin: a review of its use in the treatment of vascular occlusion after soft tissue augmentation.

PubMed

Kleydman, Kate; Cohen, Joel L; Marmur, Ellen

2012-12-01

Skin necrosis after soft tissue augmentation with dermal fillers is a rare but potentially severe complication. Nitroglycerin paste may be an important treatment option for dermal and epidermal ischemia in cosmetic surgery. To summarize the knowledge about nitroglycerin paste in cosmetic surgery and to understand its current use in the treatment of vascular compromise after soft tissue augmentation. To review the mechanism of action of nitroglycerin, examine its utility in the dermal vasculature in the setting of dermal filler-induced ischemia, and describe the facial anatomy danger zones in order to avoid vascular injury. A literature review was conducted to examine the mechanism of action of nitroglycerin, and a treatment algorithm was proposed from clinical observations to define strategies for impending facial necrosis after filler injection. Our experience with nitroglycerin paste and our review of the medical literature supports the use of nitroglycerin paste on the skin to help improve flow in the dermal vasculature because of its vasodilatory effect on small-caliber arterioles. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Rethinking the Role of Nitroglycerin Ointment in Ischemic Vascular Filler Complications: An Animal Model With ICG Imaging.

PubMed

Hwang, Catherine J; Morgan, Payam V; Pimentel, Aline; Sayre, James W; Goldberg, Robert A; Duckwiler, Gary

2016-01-01

Soft tissue dermal fillers, both temporary and permanent, are used frequently in facial rejuvenation. As the use of fillers increases, ischemic complications including skin necrosis are becoming more prevalent. In the literature, topical nitroglycerin paste has been recommended in the early treatment of patients presenting with ischemia. The purpose of this study was to evaluate the vascular perfusion effects of topical nitroglycerin paste in an animal model using indocyanine green (ICG) imaging. After Animal Research Committee approval, a rabbit ear model was used to create filler-associated skin ischemia. Ischemia was confirmed to occur after intra-arterial occlusion. Four commonly used soft tissue fillers were injected intra-arterially: Radiesse (Merz USA, Greensboro NC), Restylane (Galderma, Ft. Worth, TX), Juvederm Ultra (Allergan, Irvine CA), Belotero (Merz USA, Greensboro NC) (0.1 ml). A total of 15 ears were used, 1 control and 4 experimental per product. Thirty minutes after occlusion, nitroglycerin ointment USP, 2%(Nitro-Bid) was applied topically to the experimental ears. Vascular perfusion was evaluated with the SPY System (Novadaq Inc.) using ICG imaging. Perfusion images were obtained at baseline, immediately after, and 30 minutes after intra-arterial filler injection, and at 30, 60, 90, and 120 minutes after application of topical nitroglycerin ointment. In this rabbit ear model, no statistically significant improvement in perfusion was noted after topical application of nitroglycerin paste with ICG imaging. In addition, the skin of the rabbit ear post-nitroglycerin ointment appeared to have more of a congested appearance than the controls. Ischemic filler complications are becoming increasingly prevalent. Practitioners often treat these complications with topical nitroglycerin paste based on the knowledge that topical nitroglycerin causes vasodilation. In filler-induced tissue ischemia, however, filler product is present within arterioles. Theoretically, applying nitroglycerin paste, at least early, may not improve perfusion and could worsen ischemia with dilation of vessels and further propagation of product into the smaller arterioles and capillaries. In addition, nitroglycerin paste has systemic effects, including hypotension and dizziness, which may not be tolerated by some patients. Therefore, the authors caution the use of topical nitroglycerin paste in patients presenting with filler-associated ischemia. Further studies in the best treatment algorithms for patients presenting with ischemic complications need to be performed.

Coronary vasodilation by the use of sublingual nitroglycerin using 64-slice dual-source coronary computed tomography angiography.

PubMed

Okada, Munemasa; Nakashima, Yoshiteru; Nomura, Takafumi; Miura, Toshiro; Nao, Tomoko; Yoshimura, Masayuki; Sano, Yuichi; Matsunaga, Naofumi

2015-03-01

Sublingual nitroglycerin capsules or spray is routinely used to treat anginal attacks and to maximally dilate the epicardial coronary arteries during coronary angiography. These dilated coronary vessels have an advantage, but increased heart rates were disadvantageous for coronary computed tomography angiography (CTA). The influence of applying nitroglycerin was analyzed regarding the coronary diameter, coronary luminal attenuation, evaluable number of coronary segments, heart rate (HR), HR variability, the optimal reconstruction phase, and image scoring of CTA in the same patients using a 64-slice dual-source CT. Fifty-two patients with atypical chest pain underwent coronary CTA before and after the administration of sublingual nitroglycerin without heart rate control. The coronary diameter and luminal attenuation were measured on short-axial images in each coronary segment. The coronary vasodilation ratios (VRs) were calculated from the coronary diameters at the same location before and after the use of nitroglycerin. The local institutional review board approved this study and written informed consent was obtained from all the patients. No significant differences were noted in the HR variability or optimal reconstruction phase, despite an increase in HR after the use of nitroglycerin. Nitroglycerin significantly enlarged the coronary artery diameter, and VRs of each coronary segment ranged from 7.54% to 22.26%. As compared with baseline coronary diameter, VRs of minor segments (16.91%) were significantly larger than those of major segments (11.35%), and the magnitude of VR correlated with the baseline coronary diameter (r=-0.48, p<0.001). Coronary luminal attenuation significantly increased due to additional administration of contrast material after the use of nitroglycerin (p<0.01), but no significant difference was noted in the image quality after the use of nitroglycerin. Sublingual nitroglycerin significantly enlarged the coronary diameters, especially in peripheral small coronary arteries, and increased the evaluable number of coronary segments on coronary CTA. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Topical nitroglycerin ointment for treatment of acute hypertension in hospitalized inpatients.

PubMed

Brower, Kathryn A; Garcia, Nelson A Telles; Smith, Hayden L; Wall, Geoffrey C

2015-05-01

Hypertension in the hospital setting is common; however, guidelines provide limited guidance specific to the inpatient setting. Acute antihypertensive treatment options can be limited in this setting by monitoring requirements of intravenous medications and patients' inability to take oral medications. A possible treatment choice used to treat acute hypertension is nitroglycerin ointment. Nitroglycerin is not approved by the Food and Drug Administration for this condition, and limited evidence exists to support this indication. To evaluate the statistical and clinical effectiveness of nitroglycerin ointment as a treatment option for acute hypertension based on a 20 mm Hg or greater reduction in systolic blood pressure. A retrospective chart review at a large tertiary community teaching hospital was performed on all adult noncardiac inpatients with an episode of acute hypertension that resulted in the administration of nitroglycerin ointment. Seventy-two patients met inclusion criteria with a total of 112 applications of nitroglycerin ointment. Of the 112 applications, systolic blood pressure decreased 20 mm Hg or more in 42% of occurrences with a median decrease of 16 mm Hg. Study results suggest possible efficacy of nitroglycerin ointment for the treatment of acute hypertension in noncardiac hospitalized patients. © The Author(s) 2014.

Nitroglycerin Sublingual

MedlinePlus

Nitroglycerin sublingual tablets are used to treat episodes of angina (chest pain) in people who have coronary artery disease (narrowing of ... Nitroglycerin comes as a sublingual tablet to take under the tongue. The tablets is usually taken as needed, either 5 to 10 minutes before activities that may ...

Effects of nitroglycerin ointment on mastectomy flap necrosis in immediate breast reconstruction: a randomized controlled trial.

PubMed

Gdalevitch, Perry; Van Laeken, Nancy; Bahng, Seokjae; Ho, Adelyn; Bovill, Esta; Lennox, Peter; Brasher, Penelope; Macadam, Sheina

2015-06-01

Mastectomy flap necrosis is a common complication of immediate breast reconstruction that impacts recovery time and reconstructive success. Nitroglycerin ointment is a topical vasodilator that has been shown to improve skin flap survival in an animal model. The objective of this study was to evaluate whether the application of nitroglycerin ointment to the breast skin after mastectomy and immediate reconstruction causes a decrease in the rate of mastectomy flap necrosis compared with placebo. This study was conducted as a randomized controlled trial and included patients aged 21 to 69 years undergoing mastectomy and immediate breast reconstruction at the University of British Columbia-affiliated hospitals (Vancouver, British Columbia, Canada). Patients with a medical history that precluded the administration of nitroglycerin were excluded from the study. The target sample size was 400 patients. Nitroglycerin ointment (45 mg) or a placebo was applied to the mastectomy skin at the time of surgical dressing. The trial was stopped at the first interim analysis after 165 patients had been randomized (85 to the treatment group and 80 to the placebo group). Mastectomy flap necrosis developed in 27 patients (33.8 percent) receiving placebo and in 13 patients (15.3 percent) receiving nitroglycerin ointment; the between-group difference was 18.5 percent (p = 0.006; 95 percent CI, 5.3 to 31.0 percent). Postoperative complications were similar in both groups [nitroglycerin, 22.4 percent (19 of 85); placebo, 28.8 percent (23 of 80)]. In patients undergoing mastectomy and immediate reconstruction, there was a marked reduction in mastectomy flap necrosis in patients who received nitroglycerin ointment. Nitroglycerin ointment application is a simple, safe, and effective way to help prevent mastectomy flap necrosis. Therapeutic, I.

Treatment of proctalgia fugax with topical nitroglycerin: report of a case.

PubMed

Lowenstein, B; Cataldo, P A

1998-05-01

We report a single case of proctalgia fugax that responded to 0.3 percent nitroglycerin ointment. Case report. A single case of proctalgia fugax responded to topical application of 0.3 percent nitro glycerin ointment with no significant side effects. Nitroglycerin ointment is a newly described treatment for several painful anal conditions. We describe a single case of levator spasm or proctalgia fugax responding to topical application of nitroglycerin. This is only a single case report, and conclusive evidence awaits completion of a controlled clinical trial.

The effects of nitroglycerin during cardiopulmonary resuscitation.

PubMed

Stefaniotou, Antonia; Varvarousi, Giolanda; Varvarousis, Dimitrios P; Xanthos, Theodoros

2014-07-05

The outcome for both in-hospital and out-of hospital cardiac arrest remains dismal. Vasopressors are used to increase coronary perfusion pressure and thus facilitate return of spontaneous circulation during cardiopulmonary resuscitation. However, they are associated with a number of potential adverse effects and may decrease endocardial and cerebral organ blood flow. Nitroglycerin has a favourable haemodynamic profile which promotes forward blood flow. Several studies suggest that combined use of nitroglycerin with vasopressors during resuscitation, is associated with increased rates of resuscitation and improved post-resuscitation outcome. This article reviews the effects of nitroglycerin during cardiopulmonary resuscitation and postresuscitation period, as well as the beneficial outcomes of a combination regimen consisting of a vasopressor and a vasodilator, such as nitroglycerin. Copyright © 2014 Elsevier B.V. All rights reserved.

Stability of nitroglycerin in intravenous admixtures.

PubMed

Klamerus, K J; Ueda, C T; Newton, D W

1984-02-01

The stability of nitroglycerin in intravenous admixtures was studied. Admixtures containing nitroglycerin 400 micrograms/ml and each of seven injectable drugs in concentrations used clinically were prepared in triplicate in 5% dextrose and 0.9% sodium chloride injections. Admixtures were stored in glass bottles at room temperature for 24 hours in the upright position and then for 24 hours in the inverted position to ensure contact of the solution with the rubber stopper of the container. At 0, 24, and 48 hours, samples of each admixture were assayed by high-performance liquid chromatography for nitroglycerin concentration. The pH of one randomly chosen bottle of each admixture was measured at 0, 24, and 48 hours. A significant loss of nitroglycerin potency at 48 hours was observed only in admixtures containing phenytoin; in these solutions, a 9% decrease in initial nitroglycerin concentration was noted. Phenytoin crystallization was present in all phenytoin admixtures by 24 hours. Compared with initial values, no significant differences in the pH values of any admixture samples assayed at 24 and 48 hours were noted; however, admixtures containing phenytoin had the most alkaline pH values. Under the conditions studied, nitroglycerin concentrations remained above 90% of their initial values for 48 hours in all tested admixtures; however, phenytoin crystallization limits the stability of phenytoin admixtures.

Mechanisms of gastroprotection by transdermal nitroglycerin in the rat

PubMed Central

Calatayud, Sara; Sanz, María-Jesús; Canet, Amparo; Bello, Regina; de Rojas, Francisco Díaz; Esplugues, Juan V

1999-01-01

Nitric oxide (NO) donors prevent experimentally-induced gastric mucosal damage, but their clinical utility is limited by short duration of action or unsuitability of the pharmaceutical form employed. This study analyses the gastroprotection elicited by a clinically used mode of continuous administration of an NO donor, namely the nitroglycerin patch. Application to rats of a transdermal patch that releases doses of nitroglycerin comparable to those used in man (40, 80, 160 and 400 ng min−1 rat−1) reduced gastric damage induced by indomethacin (25 mg kg−1, p.o. or s.c.). The nitroglycerin patch (160 ng  min−1 rat−1) also diminished damage by oral administration (1 ml) of acidified bile salts (100 mg kg−1 taurocholic acid in 150 mM HCl) or 50% ethanol. Transdermal nitroglycerin (160 ng min−1 rat−1) did not influence basal gastric blood flow, as measured by lasser-doppler flowmetry, but prevented its reduction by indomethacin. Transdermal nitroglycerin (160 ng min−1 rat−1) prevented in vivo leukocyte rolling and adherence in the rat mesentery microvessels superfused with indomethacin, as evaluated by intravital microscopy. The transdermal nitroglycerin patch protects the gastric mucosa from damage by mechanisms that involve maintenance of mucosal blood flow and reduction of leukocyte-endothelial cell interaction. PMID:10455256

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs.

PubMed

Truse, Richard; Hinterberg, Jonas; Schulz, Jan; Herminghaus, Anna; Weber, Andreas; Mettler-Altmann, Tabea; Bauer, Inge; Picker, Olaf; Vollmer, Christian

2017-01-01

Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function. © 2017 S. Karger AG, Basel.

Effect of botulinum toxin A and nitroglycerin on random skin flap survival in rats.

PubMed

Ghanbarzadeh, Kourosh; Tabatabaie, Omid Reza; Salehifar, Ebrahim; Amanlou, Massoud; Khorasani, Ghasemali

2016-01-01

A suitable pharmacological substitute for the well-established surgical delay technique for random skin flaps to increase viability has been elusive. To evaluate the effects of nitroglycerin and botulinum toxin type A on random flap survival in a rat model. The present controlled experimental study was performed in the four groups of rats. One week after intervention in each group, the flap was raised and kept in situ, and flap necrosis was evaluated through follow-up. Group 1 received intradermal botulinum toxin type A (BTX-A) and topical nitroglycerin 2%; group 2 received BTX-A and topical Vaseline (Unilever, USA); group 3 received topical nitroglycerin and intradermal normal saline; and group 4 received topical Vaseline and intradermal normal saline. BTX-A reduced the area of necrosis compared with control (24% versus 56% respectively; P<0.001). Nitroglycerin application was associated with a trend toward improved flap viability (42% versus 56%; P=0.059). The combination of topical nitroglycerin and BTX-A, compared with Vaseline and BTX-A, was associated with decreased flap necrosis (16.1% versus 24%, respectively), although it was not statistically significant (P=0.45). BTX-A was effective in reducing distal flap necrosis. The effect of BTX-A was significantly more pronounced than nitroglycerin ointment.

Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock.

PubMed

Lima, Alexandre; van Genderen, Michel E; van Bommel, Jasper; Klijn, Eva; Jansem, Tim; Bakker, Jan

2014-06-19

Recent clinical studies have shown a relationship between abnormalities in peripheral perfusion and unfavorable outcome in patients with circulatory shock. Nitroglycerin is effective in restoring alterations in microcirculatory blood flow. The aim of this study was to investigate whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients. This interventional study recruited patients who had circulatory shock and who persisted with abnormal peripheral perfusion despite normalization of global hemodynamic parameters. Nitroglycerin started at 2 mg/hour and doubled stepwise (4, 8, and 16 mg/hour) each 15 minutes until an improvement in peripheral perfusion was observed. Peripheral circulation parameters included capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen saturation (StO2) during a reactive hyperemia test (RincStO2). Measurements were performed before, at the maximum dose, and after cessation of nitroglycerin infusion. Data were analyzed by using linear model for repeated measurements and are presented as mean (standard error). Of the 15 patients included, four patients (27%) responded with an initial nitroglycerin dose of 2 mg/hour. In all patients, nitroglycerin infusion resulted in significant changes in CRT, Tskin-diff, and PI toward normal at the maximum dose of nitroglycerin: from 9.4 (0.6) seconds to 4.8 (0.3) seconds (P < 0.05), from 3.3 °C (0.7 °C) to 0.7 °C (0.6 °C) (P < 0.05), and from [log] -0.5% (0.2%) to 0.7% (0.1%) (P < 0.05), respectively. Similar changes in StO2 and RincStO2 were observed: from 75% (3.4%) to 84% (2.7%) (P < 0.05) and 1.9%/second (0.08%/second) to 2.8%/second (0.05%/second) (P < 0.05), respectively. The magnitude of changes in StO2 was more pronounced for StO2 of less than 75%: 11% versus 4%, respectively (P < 0.05). Dose-dependent infusion of nitroglycerin reverted abnormal peripheral perfusion and poor tissue oxygenation in patients following circulatory shock resuscitation. Individual requirements of nitroglycerin dose to improve peripheral circulation vary between patients. A simple and fast physical examination of peripheral circulation at the bedside can be used to titrate nitroglycerin infusion.

Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock

PubMed Central

2014-01-01

Introduction Recent clinical studies have shown a relationship between abnormalities in peripheral perfusion and unfavorable outcome in patients with circulatory shock. Nitroglycerin is effective in restoring alterations in microcirculatory blood flow. The aim of this study was to investigate whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients. Methods This interventional study recruited patients who had circulatory shock and who persisted with abnormal peripheral perfusion despite normalization of global hemodynamic parameters. Nitroglycerin started at 2 mg/hour and doubled stepwise (4, 8, and 16 mg/hour) each 15 minutes until an improvement in peripheral perfusion was observed. Peripheral circulation parameters included capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen saturation (StO2) during a reactive hyperemia test (RincStO2). Measurements were performed before, at the maximum dose, and after cessation of nitroglycerin infusion. Data were analyzed by using linear model for repeated measurements and are presented as mean (standard error). Results Of the 15 patients included, four patients (27%) responded with an initial nitroglycerin dose of 2 mg/hour. In all patients, nitroglycerin infusion resulted in significant changes in CRT, Tskin-diff, and PI toward normal at the maximum dose of nitroglycerin: from 9.4 (0.6) seconds to 4.8 (0.3) seconds (P <0.05), from 3.3°C (0.7°C) to 0.7°C (0.6°C) (P <0.05), and from [log] -0.5% (0.2%) to 0.7% (0.1%) (P <0.05), respectively. Similar changes in StO2 and RincStO2 were observed: from 75% (3.4%) to 84% (2.7%) (P <0.05) and 1.9%/second (0.08%/second) to 2.8%/second (0.05%/second) (P <0.05), respectively. The magnitude of changes in StO2 was more pronounced for StO2 of less than 75%: 11% versus 4%, respectively (P <0.05). Conclusions Dose-dependent infusion of nitroglycerin reverted abnormal peripheral perfusion and poor tissue oxygenation in patients following circulatory shock resuscitation. Individual requirements of nitroglycerin dose to improve peripheral circulation vary between patients. A simple and fast physical examination of peripheral circulation at the bedside can be used to titrate nitroglycerin infusion. PMID:24946777

Effect of Shenmai injection on preventing the development of nitroglycerin-induced tolerance in rats.

PubMed

Zhou, Qian; Sun, Yan; Tan, Wangxiao; Liu, Xiao; Qian, Yuchen; Ma, Xianghui; Wang, Ting; Wang, Xiaoying; Gao, Xiumei

2017-01-01

Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance.

Effect of Shenmai injection on preventing the development of nitroglycerin-induced tolerance in rats

PubMed Central

Zhou, Qian; Sun, Yan; Tan, Wangxiao; Liu, Xiao; Qian, Yuchen; Ma, Xianghui; Wang, Ting; Wang, Xiaoying; Gao, Xiumei

2017-01-01

Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance. PMID:28453571

Leftward bulging of atrial septum is provoked by nitroglycerin and by sustained valsalva strain.

PubMed

Johansson, Magnus C; Guron, Cecilia Wallentin

2014-10-01

The motion of the interatrial septum primum (septum) is dependent on the interatrial pressure relation, normally with slightly higher pressure in the left atrium and the septum bulging toward the right atrium. The aim of this study was to explore the physiologic mechanisms that reverse interatrial pressures and provoke leftward bulging of septum (LBA). The hypothesis was that both left ventricular unloading with nitroglycerin and sustained Valsalva strain would independently provoke LBA and that their combination would further intensify the effect. Prospectively collected transesophageal echocardiography recordings from 13 patients with obstructive sleep apnea were retrospectively analyzed for the presence or absence of LBA during resting respiration and during Valsalva strain. In each condition, LBA beats were counted at time points before and after nitroglycerin spray had been administered, which enabled a comparison of the independent effects and the combined effect of the nitroglycerin and the Valsalva maneuver. An LBA beat was defined as a heartbeat displaying any LBA during the cardiac cycle. Nitroglycerin increased the proportion of LBA beats significantly during resting respiration, from 21 ± 27% to 54 ± 43% (P = .008). During Valsalva strain, the proportion increased with nitroglycerin spray from 48 ± 21% to 80 ± 17% (P = .001). After nitroglycerin administration, LBA occurred in at least three beats during strain in all Valsalva periods. Unloading of the left ventricle by nitroglycerin administration and by sustained Valsalva strain independently provoked LBA. The combination of these two interventions further intensified the effect. Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Acute effects of intracoronary nitroglycerin and diltiazem in coronary slow flow phenomenon.

PubMed

Ozdogru, Ibrahim; Zencir, Cemil; Dogan, Ali; Orscelik, Ozcan; Inanc, Mehmet Tugrul; Celik, Ahmet; Gur, Mustafa; Elbasan, Zafer; Kalay, Nihat; Oguzhan, Abdurrahman

2013-01-01

The coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder angiographically defined by delayed opacification of the distal vasculature in the absence of obstructive coronary artery disease. We aimed to investigate and compare the effects of intracoronary nitrate and diltiazem on thrombolysis in myocardial infarction frame count (TFC) in patients with CSFP during coronary angiography. Sixty patients with CSFP were randomly divided into 2 groups. The first group is nitroglycerin group with 30 patients (22 men; mean [SD] age, 50 [12] years), and the second is diltiazem group with 30 patients (27 men; mean age, 54 ± 11 years); intracoronary 5-mg diltiazem or 250-μg nitroglycerin was administered. Heart rate, systolic and diastolic blood pressures, and TFCs in all 3 coronaries were recorded before and after administering these medications. After nitroglycerin administration, systolic and diastolic blood pressures decreased, heart rates significantly increased, and TFCs decreased in all coronaries (P < 0.001 for 3 coronaries). After the application of intracoronary 5-mg diltiazem, heart rate, systolic and diastolic blood pressures, and TFCs were found significantly lower than predrug values (P < 0.001 for all values). When the percent TFC reductions, after the application of intracoronary diltiazem or nitroglycerin, in left anterior descending coronary artery, circumflex coronary artery, and right coronary artery were evaluated, diltiazem significantly reduced the TFCs of the left anterior descending coronary artery and circumflex coronary artery compared with nitroglycerin (P < 0.01 for both coronaries). Both intracoronary diltiazem and nitroglycerin improve the TFCs in CSFP, and intracoronary diltiazem is superior to nitroglycerin in reducing TFCs in CSFP.

A novel treatment for management of a trapped placenta using intracervical nitroglycerin tablets

PubMed Central

Rodgers, Blake Conley; Pasternak, Adam; Gray, Richard

2013-01-01

A 34-year-old gravida 2, para 1 woman delivered a viable male infant and developed retained placenta due to entrapment. A nitroglycerin tablet was used to relax the lower uterine segment and cervix, which allowed the placenta to pass through the cervix for delivery. The nitroglycerin tablet was placed in the cervix and held in place by the delivering physician as it dissolved. Soon after administration, the intact placenta delivered. The patient did not experience the typical side effects of headache, asymptomatic decrease in blood pressure, hypotension, palpitations or dizziness that can be associated with administration of nitroglycerin. We suspect that this novel localised route of nitroglycerin administration may be an effective management strategy to treat trapped placenta while minimising side effects. However, the outcomes of this treatment would require further study. PMID:24014558

The effects of local nitroglycerin on the surgical delay procedure in prefabricated flaps by vascular implant in rats.

PubMed

Sá, Jairo Zacchê de; Aguiar, José Lamartine de Andrade; Cruz, Adriana Ferreira; Schuler, Alexandre Ricardo Pereira; Lima, José Ricardo Alves de; Marques, Olga Martins

2012-12-01

To evaluate the effect of local nitroglycerin on the viable area of a prefabricated flap for vascular implant in rats, and to investigate the surgical delay procedure. A femoral pedicle was implanted under the skin of the abdominal wall in forty Wistar rats. The animals were divided into four groups of ten: group 1 - without surgical delay procedure and local nitroglycerin; group 2 - with surgical delay procedure, but without local nitroglycerin; group 3 - without surgical delay procedure, but with local nitroglycerin; and group 4 - with simultaneous surgical delay procedure and local nitroglycerin. The percentages of the viable areas, in relation to the total flap, were calculated using AutoCAD R 14. The mean percentage value of the viable area was 8.9% in the group 1. 49.4% in the group 2; 8.4% in the group 3 and 1.1% in the group 4. There was significant difference between groups 1 and 2 (p=0.005), 1 and 4 (p=0.024), 2 and 3 (p=0.003), 2 and 4 (p=0.001). These results support the hypothesis that the closure of the arterial venous channels is responsible for the phenomenon of surgical delay procedure. Local nitroglycerin did not cause an increase in the prefabricated viable flap area by vascular implantation and decreased the viable flap area that underwent delay procedures.

Transdermal nitroglycerin for the treatment of preterm labor: a systematic review and metaanalysis.

PubMed

Conde-Agudelo, Agustín; Romero, Roberto

2013-12-01

The purpose of this study was to evaluate the efficacy and safety of transdermal nitroglycerin as a tocolytic agent in women with preterm labor. We conducted a systematic review and metaanalysis of randomized controlled trials. Thirteen studies were included (1302 women) comparing transdermal nitroglycerin vs placebo (2 studies; n = 186); β2-adrenergic receptor agonists (9 studies; n = 1024); nifedipine (1 study; n = 50); and magnesium sulfate (1 study; n = 42). There were no significant differences between transdermal nitroglycerin and placebo for delivery within 48 hours of the initiation of treatment or at <28, <34, or <37 weeks of gestation, adverse neonatal outcomes, and neurodevelopmental status at 24 months of life. Nevertheless, 1 study found a marginally significant reduction in the risk of a composite outcome of major neonatal morbidity and perinatal death (3/74 [4.1%] vs 11/79 [13.9%]; relative risk, 0.29; 95% confidence interval, 0.08-1.00). When compared with β2-adrenergic receptor agonists, transdermal nitroglycerin was associated with a significant reduction in the risk of preterm birth at <34 and <37 weeks of gestation, admission to the neonatal intensive care unit, use of mechanical ventilation, and maternal side effects. There were no significant differences between transdermal nitroglycerin and nifedipine and magnesium sulfate in delivery within 48 hours of treatment and pregnancy prolongation, respectively. Overall, women who received transdermal nitroglycerin had a higher risk of headache. Although transdermal nitroglycerin appears to be more effective than β2-adrenergic receptor agonists, the current evidence does not support its routine use as a tocolytic agent for the treatment of preterm labor. Further double-blind placebo-controlled trials are needed. Copyright © 2013 Mosby, Inc. All rights reserved.

[Intravenous nitroglycerin infusion suppresses exercise-induced arrhythmia in patients with ischemic cardiopathy: indications for chronic treatment ].

PubMed

Bonetti, F; Margonato, A; Mailhac, A; Vicedomini, G; Cianflone, D; Scarpazza, P; Chierchia, S L

1990-05-01

In patients with ischemic heart disease and arrhythmias, selection of antiarrhythmic treatment is often difficult as it is hard to separate "primary" from ischemic arrhythmias. We studied 20 patients with ischemic heart disease, who developed ventricular arrhythmias consistently during exercise test. Exercise test was performed twice during infusion of placebo and then during intravenous administration of nitroglycerin, titrated to reduce systolic blood pressure by 10 mmHg. Exercise duration was 7.8 +/- 1.7 and 7.9 +/- 1.5 min, in the 2 placebo tests (NS). Angina developed in 5 patients and ischemic ST changes in 10. With nitroglycerin exercise duration increased to 8.4 +/- 20 min (p less than 0.05), diagnostic ST segment depression was observed in 2 patients and only 1 had angina. In all 20 patients, ventricular arrhythmias were consistently present during both tests on placebo, that were markedly reduced by nitroglycerin. In fact, ventricular ectopic beats were 455 (mean 35.8 +/- 16.8) and 418 (mean 34.4 +/- 11.1) in the 2 exercise tests with placebo, and 11 during nitroglycerin infusion (mean 0.6 +/- 0.1; p less than 0.001). Couplets were 28 and 29 during placebo (NS) and 0 during nitroglycerin (p less than 0.001). Ventricular tachycardia was present in 6 and 8 patients during placebo but in none during nitroglycerin (p less than 0.001). Reduction of exercise-induced arrhythmias was maintained during chronic treatment with oral vasodilators. Prevention of exercise-related arrhythmias by nitroglycerin infusion appears a good indicator of their ischemic origin and may provide valuable information for long-term profilaxis with oral vasodilators, then avoiding the use of antiarrhythmic agents and their potential side effects.

Contrasting effects of vasodilators on blood pressure and sodium balance in the hypertension of autonomic failure

NASA Technical Reports Server (NTRS)

Jordan, J.; Shannon, J. R.; Pohar, B.; Paranjape, S. Y.; Robertson, D.; Robertson, R. M.; Biaggioni, I.

1999-01-01

Supine hypertension, which is very common in patients with autonomic failure, limits the use of pressor agents and induces nighttime natriuresis. In 13 patients with severe orthostatic hypotension due to autonomic failure (7 women, 6 men, 72 +/- 3 yr) and supine hypertension, the effect of 30 mg nifedipine (n = 10) and 0.025 to 0.2 mg/h nitroglycerin patch (n = 11) on supine BP, renal sodium handling, and orthostatic tolerance was determined. Medications were given at 8 p.m.; patients stood up at 8 a.m. Nitroglycerin was removed at 6 a.m. Compared with placebo, nifedipine and nitroglycerin decreased systolic BP during the night by a maximum of 37 +/- 9 and 36 +/- 10 mmHg, respectively (P < 0.01). At 8 a.m., supine systolic BP was 23 +/- 7 mmHg lower with nifedipine than with placebo (P < 0.05), but was similar with nitroglycerin and placebo. Sodium excretion during the night was not reduced with nitroglycerin (0.13 +/- 0.02 mmol/mg creatinine [Cr] versus 0.15 +/- 0.03 mmol/mg Cr with placebo), but it was increased with nifedipine (0.35 +/- 0.06 mmol/mg Cr versus 0.13 +/- 0.02 mmol/mg Cr with placebo, P < 0.05). Nifedipine but not nitroglycerin worsened orthostatic hypotension in the morning. It is concluded that nifedipine and transdermal nitroglycerin are effective in controlling supine hypertension in patients with autonomic failure. However, nifedipine has a prolonged depressor effect and worsens orthostatic hypotension in the morning. The decrease in pressure natriuresis that would be expected with the substantial decrease in BP obtained with nitroglycerin and nifedipine may be offset by a direct effect of both drugs on renal sodium handling.

Nitroglycerin patch for the treatment of chondrodermatitis nodularis helicis: a new therapeutic option.

PubMed

Garrido Colmenero, Cristina; Martínez García, Eliseo; Blasco Morente, Gonzalo; Tercedor Sánchez, Jesús

2014-01-01

Chondrodermatitis nodularis helicis (CNH) is an inflammatory process that affects the skin and cartilage of the ear. At present, there are many treatment options, although they are not always effective. Based on previous studies where nitroglycerin 2% gel was used, we propose the use of nitroglycerin patches. The purpose of this study was to evaluate the effectiveness of nitroglycerin patches in treating CNH. We performed a prospective study in 11 patients diagnosed with CNH treated with nitroglycerin patches 5 mg, 12 hours a day for 2 months. The therapeutic effectivity was determined by the improvement in the appearance and symptoms of the lesion. Seven of 11 patients (63.6%) had a complete response. One of 11 patients (9%) did not respond completely and surgical treatment was performed. Two of 11 patients (18.1%) stopped the treatment because of headache. One of 11 patients (9%) did not complete the treatment because the said patient forgot to apply the patch every night. Transdermal nitroglycerin has demonstrated efficacy in the treatment of the symptoms and lesional appearance of CNH noninvasive manner. The success rate is comparable with other published methods and the rate of adverse effects is acceptable. © 2014 Wiley Periodicals, Inc.

Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes.

PubMed

Miura, Takeshi; Nishinaka, Toru; Terada, Tomoyuki; Yonezawa, Kazuya

2017-10-01

The functional genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) influences the enzymatic activities of its wild type (Glu504 encoded by ALDH2*1) and mutant type (Lys504 encoded by ALDH2*2) proteins. The enzymatic activities of mutant-type ALDH2 are limited compared with those of the wild type. ALDH2 has been suggested as a critical factor for nitroglycerin-mediated vasodilation by some human studies and in vitro studies. Currently, there is no research on direct observations of the vasodilatory effect of nitroglycerin sublingual tablets, which is the generally used dosage form. In the present study, the contribution of ALDH2 to the vasodilatory effect of nitroglycerin sublingual tablets was investigated among three genotype groups (ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2) in Japanese. The results by direct assessments of in vivo nitroglycerin-mediated dilation showed no apparent difference in vasodilation among all genotypes of ALDH2. Furthermore, to analyze the effect of other factors (age and flow-mediated dilation), multiple regression analysis and Pearson's correlation coefficient analysis were carried out. These analyses also indicated that the genotypes of ALDH2 were not related to the degree of vasodilation. These results suggest the existence of other predominant pathway(s) for nitroglycerin biotransformation, at least with regard to clinical nitroglycerin (e.g., a sublingual tablet) in Japanese subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of soluble guanylyl cyclase activator and stimulator therapy on nitroglycerin-induced nitrate tolerance in rats.

PubMed

Jabs, A; Oelze, M; Mikhed, Y; Stamm, P; Kröller-Schön, S; Welschof, P; Jansen, T; Hausding, M; Kopp, M; Steven, S; Schulz, E; Stasch, J-P; Münzel, T; Daiber, A

2015-08-01

Chronic nitroglycerin (GTN) anti-ischemic therapy induces side effects such as nitrate tolerance and endothelial dysfunction. Both phenomena could be based on a desensitization/oxidation of the soluble guanylyl cyclase (sGC). Therefore, the present study aims at investigating the effects of the therapy with the sGC activator BAY 60-2770 and the sGC stimulator BAY 41-8543 on side effects induced by chronic nitroglycerin treatment. Male Wistar rats were treated with nitroglycerin (100mg/kg/d for 3.5days, s.c. in ethanol) and BAY 60-2770 (0.5 or 2.5mg/kg/d) or BAY 41-8543 (1 and 5mg/kg/d) for 6days. Therapy with BAY 60-2770 but not with BAY 41-8543 improved nitroglycerin-triggered endothelial dysfunction and nitrate tolerance, corrected the decrease in aortic nitric oxide levels, improved the cGMP dependent activation of protein kinase I in aortic tissue and reduced vascular, cardiac and whole blood oxidative stress (fluorescence and chemiluminescence assays; 3-nitrotyrosine staining). In contrast to BAY 41-8543, the vasodilator potency of BAY 60-2770 was not impaired in isolated aortic ring segments from nitrate tolerant rats. sGC activator therapy improves partially the adverse effects of nitroglycerin therapy whereas sGC stimulation has only minor beneficial effects pointing to a nitroglycerin-dependent sGC oxidation/inactivation mechanism contributing to nitrate tolerance. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmacodynamics and effectiveness of topical nitroglycerin at lowering blood pressure during autonomic dysreflexia.

PubMed

Solinsky, R; Bunnell, A E; Linsenmeyer, T A; Svircev, J N; Engle, A; Burns, S P

2017-10-01

Secondary analysis of prospectively collected observational data assessing the safety of an autonomic dysreflexia (AD) management protocol. To estimate the time to onset of action, time to full clinical effect (sustained systolic blood pressure (SBP) <160 mm Hg) and effectiveness of nitroglycerin ointment at lowering blood pressure for patients with spinal cord injuries experiencing AD. US Veterans Affairs inpatient spinal cord injury (SCI) unit. Episodes of AD recalcitrant to nonpharmacologic interventions that were given one to two inches of 2% topical nitroglycerin ointment were recorded. Pharmacodynamics as above and predictive characteristics (through a mixed multivariate logistic regression model) were calculated. A total of 260 episodes of pharmacologically managed AD were recorded in 56 individuals. Time to onset of action for nitroglycerin ointment was 9-11 min. Time to full clinical effect was 14-20 min. Topical nitroglycerin controlled SBP <160 mm Hg in 77.3% of pharmacologically treated AD episodes with the remainder requiring additional antihypertensive medications. A multivariate logistic regression model was unable to identify statistically significant factors to predict which patients would respond to nitroglycerin ointment (odds ratios 95% confidence intervals 0.29-4.93). The adverse event rate, entirely attributed to hypotension, was 3.6% with seven of the eight events resolving with close observation alone and one episode requiring normal saline. Nitroglycerin ointment has a rapid onset of action and time to full clinical effect with high efficacy and relatively low adverse event rate for patients with SCI experiencing AD.

A comparison of the pharmacokinetic and pharmacodynamic properties of nitroglycerin according to the composition of the administration set: A preliminary study.

PubMed

Kim, Choon Ok; Song, Jeongyun; Min, Ji Young; Park, Su Jung; Lee, Hye Mi; Byon, Hyo-Jin

2018-03-01

There is a risk of drug sorption into an intravenous administration set composed of polyvinyl chloride (PVC), polyurethane (PU), or polyolefin (PO). This has implications on the dose of the active ingredient the patient receives, and thus therapeutic success. This study aimed to determine the plasma concentration of nitroglycerin and the effect of nitroglycerin on patients based on the composition of the administration set. Using a randomized, open-labeled, 3 × 3 crossover method, 9 volunteers were assigned to 3 groups. In period I, nitroglycerin (100 μg/mL) was infused via a PVC- (group A), PU- (group B), or PO-based (group C) administration set. In period II, PU- (group A), PO- (group B), and PVC-based (group C) administration sets were used, and in period III, PO- (group A), PVC- (group B), and PU-based (group C) administration sets were used. The rate of drug administration in all periods was 12 mL/hour for 30 minutes using an infusion pump. Blood samples were collected, and the plasma concentrations of nitroglycerin were analyzed using validated high-performance liquid chromatography coupled with tandem mass spectrometry. Blood pressure was determined using a sphygmomanometer applied to the other upper arm at an interval of 5 minutes. We observed that the mean plasma concentration of nitroglycerin over time when administered using a PO-based tube was higher than that when using a PU- or PVC-based tube. When the percent change of the mean arterial pressure from baseline at each time point was compared among groups, there were statistically significant differences between PU and PO or PVC at most points during nitroglycerin infusion. Our results showed higher nitroglycerin plasma concentration and lower arterial pressure when a PO-based administration set was used than when a PVC- or PU-based administration set was used. PO-based administration sets may be more appropriate for nitroglycerin administration compared to those composed of PVC or PU.

Stability of nitroglycerin 110 mcg/mL stored in polypropylene syringes.

PubMed

McCluskey, Susan V; Vu, Nicole; Rueter, John

2013-01-01

Various angiography procedures at Mayo Clinic (Rochester campus) require small bolus doses of injectable nitroglycerin. Commercially acquired containers of injectable nitroglycerin provide excessive amounts of drug for these procedural needs, so syringes were chosen as a container for dispensing of the dose needed. Due to nitroglycerin's known chemical attributes of volatility and sorption to plastic surfaces, careful consideration of the stability needs to be taken into account when storing in a syringe. Since there is a lack of stability information in the literature, we studied the stability of nitroglycerin in polypropylene syringes over 90 days. Methods used for this study consisted of a validated stability-indicating high-performance liquid chromatographic assay, visual appearance, and pH. Samples were stored protected from light at ambient controlled temperature and consisted of nitroglycerin 110 mcg/mL in 5% dextrose injection 10.1 mL in 12 mL Terumo polypropylene syringes. Samples were tested at intervals up to 90 days. Results from the visual portion of the study showed clear, colorless, and particulate-free solutions throughout the 90-day study period. The pH results started at 4.27 +/- 0.13 (day 0) and ranged from 4.19 +/- 0.17 to 4.92 +/- 0.43 throughout the study period. Potency test results revealed a day 0 concentration of 104.242 +/- 0.193 mcg/mL (batch 1) and 122.483 +/- 0.168 mcg/mL (batch 2). Results trended downward with percentage of day 0 concentration of 92.2% +/- 2.4% at day 14 and of 81.4% +/- 4.9% at day 90. Chromatographic profiles of the samples exhibited insignificant changes over the study period. The nitroglycerin peak was spectrally pure based on peak-purity analysis, suggesting that sorption to the polypropylene syringe is one possible reason for the concentration decline over time, but nitroglycerin is a volatile compound and loss through vaporization cannot be ruled out. Nitroglycerin 110 mcg/mL in 5% dextrose injection, packaged in Terumo polypropylene syringes with 10.1 mL aliquots, maintained 90% of syringe potency for 24 days when stored protected from light under controlled ambient conditions.

A comparison of the pharmacokinetic and pharmacodynamic properties of nitroglycerin according to the composition of the administration set

PubMed Central

Kim, Choon Ok; Song, Jeongyun; Min, Ji Young; Park, Su Jung; Lee, Hye Mi; Byon, Hyo-Jin

2018-01-01

Abstract Background: There is a risk of drug sorption into an intravenous administration set composed of polyvinyl chloride (PVC), polyurethane (PU), or polyolefin (PO). This has implications on the dose of the active ingredient the patient receives, and thus therapeutic success. This study aimed to determine the plasma concentration of nitroglycerin and the effect of nitroglycerin on patients based on the composition of the administration set. Methods: Using a randomized, open-labeled, 3 × 3 crossover method, 9 volunteers were assigned to 3 groups. In period I, nitroglycerin (100 μg/mL) was infused via a PVC- (group A), PU- (group B), or PO-based (group C) administration set. In period II, PU- (group A), PO- (group B), and PVC-based (group C) administration sets were used, and in period III, PO- (group A), PVC- (group B), and PU-based (group C) administration sets were used. The rate of drug administration in all periods was 12 mL/hour for 30 minutes using an infusion pump. Blood samples were collected, and the plasma concentrations of nitroglycerin were analyzed using validated high-performance liquid chromatography coupled with tandem mass spectrometry. Blood pressure was determined using a sphygmomanometer applied to the other upper arm at an interval of 5 minutes. Results: We observed that the mean plasma concentration of nitroglycerin over time when administered using a PO-based tube was higher than that when using a PU- or PVC-based tube. When the percent change of the mean arterial pressure from baseline at each time point was compared among groups, there were statistically significant differences between PU and PO or PVC at most points during nitroglycerin infusion. Conclusion: Our results showed higher nitroglycerin plasma concentration and lower arterial pressure when a PO-based administration set was used than when a PVC- or PU-based administration set was used. PO-based administration sets may be more appropriate for nitroglycerin administration compared to those composed of PVC or PU. PMID:29489681

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

PubMed

Tomoda, Takeshi; Kato, Hironari; Mizukawa, Sho; Muro, Shinichiro; Akimoto, Yutaka; Uchida, Daisuke; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

2016-01-01

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

Nitroglycerin hypotensive effect and application in a combined surgery for reconstruction after ipsilateral maxillectomy and orbit evisceration.

PubMed

Sun, Yuhang; Dong, Xiaohui; Zhang, Guofeng; An, Jing; Yuan, Haojun

2017-05-01

The oral and maxillofacial region is rich in blood, and it is often difficult to stop bleeding during the operation of maxilla. Nitroglycerin is one of the most commonly used antihypertensive drugs in our hospital. We observed the effect of controlled hypotension in patients with maxillary resection. In group N, the patients had different degrees of tachycardia after using nitroglycerin only. In addition, nitroglycerin has the characteristics of rapid drug resistance. A combined reversed temporal muscle flap and random forehead flap technique was performed successfully to reconstruct the large defect after ipsilateral maxillectomy and orbit evisceration. There were 43 cases used this method during 2014-2016 without large side effects.

Comparison of direct effects of clinically available vasodilators; nitroglycerin, nifedipine, cilnidipine and diltiazem, on human skeletonized internal mammary harvested with ultrasonic scalpel.

PubMed

Fukuda, Shoji; Nakamura, Yuji; Egi, Koso; Fujioka, Shunichiro; Nagasaka, Satoshi; Minh, Pham Ngoc; Toguchi, Koji; Wada, Takeshi; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Mizoue, Tetsuya; Takazawa, Kenji; Hosaka, Shigeru; Sugiyama, Atsushi

2016-10-01

Direct vasodilator effects of nitroglycerin, nifedipine, cilnidipine and diltiazem on human skeletonized internal mammary artery graft harvested with ultrasonic scalpel were assessed in the presence of 0.1 or 0.2 µM of noradrenaline. Ring preparations were made of distal end section of the bypass grafts, and those dilated by acetylcholine were used for assessment. Each drug dilated the artery in a concentration-related manner (0.01-10 µM, n = 6 for each drug) with a potency of nitroglycerin > nifedipine = cilnidipine > diltiazem. These results indicate that nitroglycerin can be useful for treating internal mammary artery spasm, that clinical utility of diltiazem may not depend on its vasodilator effect on the bypass graft, and that cilnidipine as well as nifedipine will have anti-spastic action which is in the middle between those of nitroglycerine and diltiazem.

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer.

PubMed

Arrieta, Oscar; Blake, Mónika; de la Mata-Moya, María Dolores; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

2014-05-01

Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Nitroglycerin mediated dilation evaluated by ultrasound is associated with sTWEAK in hemodialysis patients.

PubMed

Rusu, Crina Claudia; Ghervan, Liviu; Racasan, Simona; Kacsa, Ina; Moldovan, Diana; Potra, Alina; Bondor, Cosmina; Anton, Florin; Patiu, Ioan Mihai; Caprioara, Mirela Gherman

2016-03-01

The main cause of death in hemodialysis (HD) patients is cardiovascular disease. Ultrasound assessment of the brachial artery dysfunction is easily achievable and can non-invasively detect atherosclerosis in various stages. In HD patients the cardiovascular risk profile is different and the determinants of brachial arterial function can be distinct comparing with general population. The aim of the study is to assess the determinants of arterial brachial function (flow-mediated and nitroglycerin-mediated dilation) evaluated by ultrasound in HD patients and their relation with tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) described as atherosclerotic marker in chronic kidney disease patients. We conducted a cross-sectional observational study on 54 hemodialysis patients. We recorded clinical and biological data and we measured sTWEAK serum levels by ELISA. We evaluated the arterial brachial function by measurement of flow-mediated and nitroglycerin-mediated dilation, using B mode ultrasound. The determinants of flow-mediated dilation were: Kt/V (r=0.47, p<0.001), LDL-cholesterol (r=0.29, p=0.04), and total cholesterol (r=0.31, p=0.02). Flow-mediated dilation correlated with nitroglycerin-mediated dilation (r=0.70, p<0.001). In multivariate analysis kt/V was the only significant predictor for flow-mediated dilation (p=0.04). Nitroglycerin-mediated dilation correlates with sTWEAK (r=-0.30, p=0.03), systolic blood pressure (r=-0.28, p=0.04) and pulse pressure (r=-0.31, p=0.02). In multivariate analysis sTWEAK was the only significant predictor for nitroglycerin-mediated dilation (p=0.04). The main determinant of nitroglycerin-mediated dilation was sTWEAK. In addition, decreased nitroglycerin-mediated dilation was associated with higher systolic blood pressure and pulse pressure. The main determinant of FMD was Kt/V. Increased flow-mediated dilation was associated with better dialysis efficiency and high total cholesterol and LDL-cholesterol.

Beneficial effects of intracoronary nicorandil on microvascular dysfunction after primary percutaneous coronary intervention: demonstration of its superiority to nitroglycerin in a cross-over study.

PubMed

Ito, Noritoshi; Nanto, Shinsuke; Doi, Yasuji; Kurozumi, Yuma; Natsukawa, Tomoaki; Shibata, Hiroyuki; Morita, Masaya; Kawata, Atsushi; Tsuruoka, Ayumu; Sawano, Hirotaka; Okada, Ken-ichiro; Sakata, Yasuhiko; Kai, Tatsuro; Hayashi, Toru

2013-08-01

In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 μg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.

Using Multidetector Computed Tomography in a Swine Model to Assess the Effects of Sublingual Nitroglycerin and Intravenous Adenosine on Epicardial Coronary Arteries

PubMed Central

Clarkson, Wesley A; Restrepo, Carlos Santiago; Bauch, Terry D; Rubal, Bernard J

2009-01-01

This study examines the effects of intravenous infusion of adenosine and sublingual nitroglycerin on coronary angiograms obtained by current-generation multidetector computed tomography. We assessed coronary vasodilation at baseline and after intravenous adenosine (140 µg/kg/min) or sublingual nitroglycerin spray (800 µg) in 7 female swine (weight, 40.9 ± 1.4 kg) by using electrocardiogram-gated coronary angiography with a 64-detector scanner (rotation time, 400 ms; 120kV; 400 mA) and intravenous contrast (300 mg/mL iohexol, 4.5 mL/s, 2 mL/kg). Cross-sectional areas of segments in the left anterior descending, circumflex, and right coronary arteries were evaluated in oblique orthogonal views. Images were acquired at an average heart rate of 73 ± 11 beats per minute. Changes in aortic pressure were not significant with nitroglycerin but decreased (approximately 10%) with adenosine. Of the 76 segments analyzed (baseline range, 2 to 39 mm2), 1 distal segment could not be assessed after adenosine. Segment cross-sectional area increased by 11.3% with nitroglycerin but decreased by 9.6% during adenosine infusion. The results of the present study are consistent with the practice of using sublingual nitroglycerin to enhance visualization of epicardial vessels and suggest that intravenous adenosine may hinder coronary artery visualization. This study is the first repeated-measures electrocardiogram-gated CT evaluation to use the same imaging technology to assess changes in coronary cross-sectional area before and after treatment with a vasodilator. The nitroglycerin-associated changes in our swine model were modest in comparison with previously reported human studies. PMID:20034433

Vasopressin and nitroglycerin decrease portal and hepatic venous pressure and hepato-splanchnic blood flow.

PubMed

Wisén, E; Svennerholm, K; Bown, L S; Houltz, E; Rizell, M; Lundin, S; Ricksten, S-E

2018-03-26

Various methods are used to reduce venous blood pressure in the hepato-splanchnic circulation, and hence minimise blood loss during liver surgery. Previous studies show that combination of vasopressin and nitroglycerin reduces portal pressure and flow in patients with portal hypertension, and in this study we investigated this combination in patients with normal portal pressure. In all, 13 patients were studied. Measurements were made twice to confirm baseline (C1 and BL), during vasopressin infusion 4.8 U/h (V), and during vasopressin infusion combined with nitroglycerin infusion (V + N). Portal venous pressure (PVP), hepatic venous pressure (HVP), central haemodynamics and arterial and venous blood gases were obtained at each measuring point, and portal (splanchnic) and hepato-splanchnic blood flow changes were calculated. Vasopressin alone did not affect PVP, whereas HVP increased slightly. In combination with nitroglycerin, PVP decreased from 10.1 ± 1.6 to 8.9 ± 1.3 mmHg (P < 0.0001), and HVP decreased from 7.9 ± 1.9 to 6.2 ± 1.3 mmHg (P = 0.001). Vasopressin reduced portal blood flow by 47 ± 19% and hepatic venous flow by 11 ± 18%, respectively. Addition of nitroglycerin further reduced portal- and hepatic flow by 55 ± 13% and 30 ± 13%, respectively. Vasopressin alone had minor effects on central haemodynamics, whereas addition of nitroglycerin reduced cardiac index (3.2 ± 0.7 to 2.7 ± 0.5; P < 0.0001). The arterial-portal vein lactate gradient was unaffected. The combination of vasopressin and nitroglycerin decreases portal pressure and hepato-splanchnic blood flow, and could be a potential treatment to reduce bleeding in liver resection surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Viable myocardium scintigraphy with intravenous nitroglycerine by computed tomography with Tc-99m (MIBI).

PubMed

Ramos Filho, José; Nascimento, Marcos Welber; Silva, Rafael Mariano Gislon da; Camargo, Thiago Negrini de; Almeida, Roberto Simões de; Lima, Eloá Jacinto

2008-09-01

The selection of patients with chronic coronary disease for recanalization is based on the detection of the affected myocardium that is potentially viable. To evaluate the potentially viable ischemic myocardium through single photon emission computed tomography (SPECT) with MIBI after a maximum tolerated dose of I.V. nitroglycerin. We prospectively investigated by SPECT with Tc-99m (MIBI), from April 2004 to November 2005, 40 patients (mean age: 62 +/- 8.9 yrs, 30 men) with coronary obstruction demonstrated angiographically; the myocardium scintigraphy was carried out at rest and after intravenous (I.V.) nitroglycerin, which was started at a dose of 1 microg/kg/min and increased every minute until the systolic blood pressure decreased by 20 mmHg. The decrease in the perfusion of the segments was classified as moderate or severe and compared after the nitroglycerin. The angiographic, hemodynamic and myocardial perfusion variables were analyzed. We analyzed 680 myocardial segments at rest: 538 with a homogenous distribution and 142 with hypoperfusion (54 with moderate and 88 with severe decrease). After the nitroglycerin, there was an increase in the perfusion in 19 (47.5%) of 40 patients and 55 of 142 segments became viable: 33 (61.1%) with moderate and 22 (25%) with severe decrease; both presented a significant increase in the radiotracer distribution (p < 0.001, Chi-square). One of the components with Tc-99m is Tc-99m 2-methoxy-isobutyl-isonitrile (MIBI), which, when used with an optimized dose of I.V. nitroglycerin, can increase the radiotracer uptake in areas with moderate and severe hypoperfusion. The results of the present study suggest the increase in the Tc-99m (MIBI) sensitivity by nitroglycerin for the detection of viable myocardium.

The effects of repeated nitroglycerin administrations in rats; modeling migraine-related endpoints and chronification.

PubMed

Harris, Hannah M; Carpenter, Jessica M; Black, Jonathan R; Smitherman, Todd A; Sufka, Kenneth J

2017-06-01

Rodent models typically use a single nitroglycerin injection to induce migraine, yet migraine in clinical populations presents as recurrent episodes. Further, these models quantify behavioral endpoints that do not align with the clinical features of episodic migraine or migraine chronification and therefore may limit translational relevance. Rats received 5 nitroglycerin (10mg/kg/2ml), propylene glycol/ethanol vehicle, or saline injections every third day over 15days. Behavioral endpoints were assessed 110min post nitroglycerin administration and included time spent light/dark chambers for photophobia as well as activity, facial pain expressions, and tactile allodynia. Animals administered nitroglycerin displayed photophobia, decreased activity, and increased facial pain expression. Similar alterations in photophobia and activity were seen in the vehicle treated animals, but these tended to diminish by the 4th or 5th injection. The presentation of spontaneous tactile allodynia was observed in the nitroglycerin group by the 5th episode. Most NTG migraine models entail a single NTG administration and quantification of evoked allodynia. This paradigm employs recurring NTG episodes and clinically-relevant measures of photophobia, hypoactivity and facial grimace endpoints as well as introduces a novel arena apparatus to quantify spontaneous allodynia. This repeated NTG procedure and endpoint measures aligns with the frequency and clinical presentation of episodic migraine and its chronification, respectively. Further, propylene glycol ethanol vehicle contributes to migraine endpoints. Copyright © 2017 Elsevier B.V. All rights reserved.

Intra-arterial nitroglycerin for intra-operative arterial vasospasm during pediatric renal transplantation.

PubMed

Penna, Frank J; Harvey, Elizabeth; John, Philip; Armstrong, Derek; Luginbuehl, Igor; Odeh, Rakan I; Alyami, Fahad; Koyle, Martin A; Lorenzo, Armando J

2016-05-01

Intra-operative arterial vasospasm during pediatric renal transplantation is an urgent clinical situation resulting in end-organ ischemia, associated changes in parenchymal turgor and color, diminished flow on ultrasound, and if left untreated, allograft loss. We hypothesized that intra-operative intra-arterial injection of nitroglycerin would reverse vasospasm and improve renal perfusion. A three-yr-old girl with end-stage renal disease due to autosomal recessive polycystic kidney disease on peritoneal dialysis underwent deceased donor renal transplantation. After optimal immediate reperfusion and hemodynamic parameters, the kidney lost turgor and became mottled in appearance despite adequate hilar arterial and venous Doppler waveforms. Two aliquots of 40 μg (0.4 mL of a 100 μg/mL) nitroglycerin solution were injected directly into the renal artery 10 min apart. Nitroglycerin resulted in dramatic change in the consistency and appearance of the allograft. An improvement in renal blood flow was demonstrated by ultrasound after the second intra-arterial nitroglycerin injection with only a transient decrease in systemic arterial blood pressure. The child experienced normal allograft perfusion on serial postoperative ultrasounds, with a prompt decrease in serum creatinine and excellent diuresis. Intra-arterial nitroglycerin is a promising option for intra-operative arterial vasospasm during pediatric renal transplantation with objective improvement in blood flow and perfusion. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Physiology of Angina and Its Alleviation With Nitroglycerin

PubMed Central

Williams, Rupert; Lockie, Timothy; Khawaja, Muhammed Z.; De Silva, Kalpa; Lumley, Matthew; Patterson, Tiffany; Arri, Satpal; Ihsan, Sana; Ellis, Howard; Guilcher, Antoine; Clapp, Brian; Chowienczyk, Philip J.; Plein, Sven; Perera, Divaka; Marber, Michael S.; Redwood, Simon R.

2017-01-01

Background: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Methods: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Results: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity–pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. Conclusions: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies. PMID:28468975

Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise.

PubMed

Asrress, Kaleab N; Williams, Rupert; Lockie, Timothy; Khawaja, Muhammed Z; De Silva, Kalpa; Lumley, Matthew; Patterson, Tiffany; Arri, Satpal; Ihsan, Sana; Ellis, Howard; Guilcher, Antoine; Clapp, Brian; Chowienczyk, Philip J; Plein, Sven; Perera, Divaka; Marber, Michael S; Redwood, Simon R

2017-07-04

The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Patients continued to exercise after nitroglycerin administration with less ST-segment depression ( P =0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P =0.030) and myocardial oxygen demand were seen (tension-time index, P =0.024; rate-pressure product, P =0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P =0.017). Exercise reduced peripheral arterial wave reflection ( P <0.05), which was not further augmented by the administration of nitroglycerin ( P =0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity-pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P <0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies. © 2017 The Authors.

Effects of autogenic training on nitroglycerin-induced headaches.

PubMed

Juhasz, Gabriella; Zsombok, Terezia; Gonda, Xenia; Nagyne, Nora; Modosne, Edit; Bagdy, Gyorgy

2007-03-01

To investigate the prophylactic and acute effects of autogenic training (AT) during a nitroglycerin-induced migraine attack. Thirty female migraineurs (without aura) and 11 controls participated in the study. Of these, 11 migraineurs and 5 controls practiced AT regularly for at least 6 months prior to and during the sublingual nitroglycerin test. Headache intensity and characteristics were recorded with a standardized method. During the nitroglycerin challenge, blood was collected for plasma cortisol determination and blood pressure and pulse rate were recorded. As a long-term preventive treatment, AT significantly decreased the mean headache frequency and intensity (P = .001) compared to the pretreatment period in the migraineurs who regularly practiced AT (n = 11). During the nitroglycerin challenge, AT successfully attenuated the nitroglycerin-induced acute decrease in blood pressure and pulse rate (P = .013; n = 16 AT subjects vs n = 25 non-AT subjects). However, it was not effective in preventing immediate headache (P = .71), did not decrease the frequency of acute migraine attacks (P = .79), and could not alleviate acute migraine pain (P = .78; n = 16 AT subjects vs n = 25 non-AT subjects). Plasma cortisol concentration significantly increased (P = .003) during the acute migraine attack (n = 22), and migraine intensity correlated with plasma cortisol elevations (P < .001; n = 41) and showed a tendency of negative correlation with morning plasma cortisol concentration (P = .08; n = 41). However, AT did not alter plasma cortisol responses (P = .99; n = 16 AT subjects vs n = 25 non-AT subjects). (1) The long-term AT therapy proved to be a significantly effective preventive intervention in migraine sufferers. We hypothesized that this long-term effect of AT is based on modulation of the pain anticipation system, which is strongly correlated with function of the anterior cingulate cortex. (2) We demonstrated that AT could not alter the nitroglycerin-induced acute migraine attacks, which are directly related to the dysfunctional brainstem activation according to previous studies. (3) Our results suggested that there are multiple, complex relationships between cortisol responses and migraine pain, which are possibly mediated by the brain serotonergic system. (4) In addition, our results provide further evidence that nitroglycerin-induced vasodilatation is not directly connected to either immediate headache or delayed migraine attack.

Compromised breast flap treated with leech therapy, hyperbaric oxygen, pentoxifylline and topical nitroglycerin: A case report.

PubMed

Moffat, Andrew D; Weaver, Lindell K; Tettelbach, William H

2015-01-01

Hyperbaric oxygen (HBO2) is often indicated in compromised surgical flaps. Although limited to animal models and human case reports, the utilization of leech therapy (Hirudo medicinalis) with HBO2 provides better outcomes than each modality alone. Topical nitroglycerin and pentoxifylline are also frequently used adjunctively for compromised flaps. We present a case of successful breast flap salvage utilizing a combination of leech therapy, HBO2, topical nitroglycerin and pentoxifylline. A 34-year-old female, one day post-status cosmetic breast reduction mammoplasty developed a dusky discoloration of the left nipple areolar complex, indicating imminent flap failure. The patient was immediately treated with topical nitroglycerin, oral pentoxifylline, and referred for HBO2. After her first HBO2 treatment, there was clinical improvement to the superior portion of the areolar flap, with little improvement inferiorly where the discoloration had remained essentially unchanged. To address this, we added leech therapy and discontinued the topical nitroglycerin. Ceftriaxone for Aeromonas prophylaxis was started, and leeches were attached two at a time and removed from the area once feeding had ceased. These were applied three times per day for three days while receiving HBO2 twice per day for six days. The patient's flap improved and completely healed by Week 8 without need for further surgery. This is the first case to our knowledge of successful breast flap salvage using a combination of leech therapy, HBO2, topical nitroglycerin and pentoxifylline.

Topical Non-Iontophoretic Application of Acetylcholine and Nitroglycerin via a Translucent Patch: A New Means for Assessing Microvascular Reactivity

PubMed Central

Schonberger, Robert B.; Worden, William S.; Shahmohammadi, Kaveh; Menn, Kirsten; Silverman, Tyler J.; Stout, Robert G.; Shelley, Kirk H.; Silverman, David G.

2007-01-01

Objective: Assessments of endothelial cell function with acetylcholine have typically used systemic, regional intra-arterial, or iontophoretic delivery of drug. Each of these techniques induces systemic and/or local changes that compromise their safety or effectiveness. Using translucent drug preparations applied under laser Doppler flowmetry (LDF) probes, we tested whether local vasodilation can be induced with non-iontophoretic transdermal delivery of acetylcholine and how such dilation would compare to the dilation achieved with topical nitroglycerin in healthy volunteers. Methods: Ten subjects without known vascular disease were recruited for LDF monitoring at sites of drug application for this preliminary investigation. Topical acetylcholine chloride, nitroglycerin, and placebo were applied via translucent patches to the forehead directly below LDF probes. Results: LDF readings increased by 406 percent (245 percent to 566 percent) and 36 percent (26 percent to 46 percent), respectively, at the acetylcholine and placebo sites (p = .005 by Wilcoxon Signed Rank Test (WSRT) for acetylcholine vs. placebo); and they increased by 365 percent (179 percent to 550 percent) at the nitroglycerin site (p = .005 by WSRT for nitroglycerin vs. placebo; p = .6 vs. acetylcholine). Conclusion: Transdermal delivery of acetylcholine can induce significant local vasodilatory responses comparable to those achieved with nitroglycerin without requiring iontophoresis. The means of transdermal delivery and monitoring described herein may constitute a new minimally invasive way to interrogate the microvasculature and thereby assess the microcirculatory changes induced by various disorders and therapeutic interventions. PMID:17876370

Allopurinol prevents nitroglycerin-induced tolerance in rat thoracic aorta.

PubMed

Azarmi, Yadollah; Babaei, Hossein; Alizadeh, Fatemeh; Gharebageri, Afsaneh; Fouladi, Daniel F; Nikkhah, Elhameh

2014-02-01

Xanthine oxidase is an important source of reactive oxygen species; so, it may play a role in the pathogenesis of endothelium dysfunction and its consequences. Allopurinol, a purine analog, is a famous xanthine oxidase inhibitor. This study aimed to investigate possible effects of allopurinol on nitroglycerin tolerance, vasoconstriction, and vasorelaxation in rat aortic ring. Using thoracic aortic rings obtained from male Wistar rats, the effect of allopurinol was examined on nitroglycerin-induced tolerance. In addition, changes of vasoconstriction (by using KCl and phenylephrine) and vasorelaxation (by using carbachol, sodium nitroprusside, and nitroglycerin) were also measured and compared between tissues treated with and without allopurinol. All 3 concentrations of allopurinol (50, 100, and 150 μM) significantly acted against the development of nitroglycerin-induced tolerance in comparison with controls. In terms of vasoconstriction and vasorelaxation, the effect of allopurinol was significant only on carbachol-induced (endothelium related) vasorelaxation in a dose-dependent manner. In conclusion, although allopurinol had no significant effect on the contractile response of the aorta, in accord with the previous data, it significantly intensified endothelium-dependent vasodilation. The inhibitory effect of allopurinol against the development of nitrate-induced tolerance may suggest its clinical benefit and is worth to be studied more extensively.

Innovative Approach to Preparing Radial Artery Cocktails in Response to Manufacturer Shortages of Nitroglycerin and Verapamil

PubMed Central

Parbhoo, Rupal K.; Wetz, Karen; Tschampel, Marva; Pompili, Vincent; Schenko, Elena; Mavko, Lou

2014-01-01

Abstract Background: Transradial access has gained popularity over transfemoral access for cardiac catheterization, because of the decreased risk of bleeding, time to ambulation, and length of stay leading to improved patient satisfaction. One disadvantage of the radial artery approach is vasospasm, which can be prevented with the administration of verapamil and nitroglycerin in a pre- and postradial cocktail. Unfortunately, there have been manufacturer shortages for both of these medications. Methods: The utilization of radial artery cocktails and other nitroglycerin compounding practices were evaluated in response to cost containment and waste reduction initiatives and to medication shortages. Results: A modified process for supplying verapamil and nitroglycerin for the transradial approach via separate syringes enabled physicians to have quick access to the medications and to customize the cocktail based on the patient’s needs. This process also decreased costs and minimized wastage. The change in practice decreased waste from 44% for preradial cocktail syringes and 66% for postradial cocktail syringes to 8.7%. Discussion: This process for supplying the medications necessary to perform a radial artery catheterization and intracoronary nitroglycerin has allowed for conservation of commercial product supply. PMID:25477581

[THE INFLUENCE OF NITROGLYCERIN ON SPECTRAL AND OXYGEN-BINDING CHARACTERISTICS OF HUMAN INTRACELLULAR HEMOGLOBIN.

PubMed

Kalaeva, E A; Artyukhov, V G; Putintseva, O V; Polyubez'eva, A I

2016-01-01

The spectral and oxygen-binding characteristics of human intracellular hemoglobin in the presence of nitroglycerin at concentrations of 5 ng/mL and 5 μg/mL have been studied. Short incubation (20 min) of erythrocytes with the drug led increasing hemoglobin affinity to oxygen and weakening of cooperative interactions in hemoprotein molecules. As a result, the amount of O(2) supplied to tissues in the process of gas exchange decreased by 23.96% (5 ng/mL) and 26.68% (5 μg/ml), p < 0.05. Incubation of cells for 24 h resulted in oxidation of the heme iron atom, accumulation of methemoglobin, and partial hemolysis. Nitroglycerin reduces the intensity of oxidative processes. However, no dependence of the degree of changes in the physical and chemical properties of hemoglobin on the concentration of nitroglycerin was found.

Pharmaceutical considerations of nitroglycerin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yacobi, A.; Amann, A.H.; Baaske, D.M.

1983-04-01

During the past few years, there have been rapid changes in the pharmaceutical uses of nitroglycerin. New dosage forms and new delivery systems have become available, which have resulted in potential confusion to all concerned with the proper use of these systems. The goal of this review is to prevent confusion and to bring all the relevant information together. The various analytical techniques available for quality control of the dosage forms and for the study of the pharmacokinetics are reviewed, with the intent of enabling the reader to identify pertinent references rapidly. The interaction of nitroglycerin with packaging and plasticmore » delivery devices is also reviewed so that the reader can make informed choices. Finally, the clinical pharmacy and pharmacokinetics are reviewed so as to bring the reader up to date in that area. After reading this article, the areas of nitroglycerin research that still need to be explored should be apparent.« less

Intravenous nitroglycerin for external cephalic version: a randomized controlled trial.

PubMed

Hilton, Jennifer; Allan, Bruce; Swaby, Cheryl; Wahba, Raouf; Wah, Raouf; Jarrell, John; Wood, Stephen; Ross, Sue; Tran, Quynh

2009-09-01

To estimate whether treatment with intravenous nitroglycerin for uterine relaxation increases the chance of successful external cephalic version. Two double-blind, randomized clinical trials were undertaken: one in nulliparous women and a second in multiparous women. Women presenting for external cephalic version at term were eligible to participate. The primary outcome was immediate success of external cephalic version. Other outcomes were presentation at delivery, cesarean delivery rate, and side effects and complications. Sample size calculations were based on a 100% increase in success of external cephalic version with a one-sided analysis and alpha=0.05 (80% power). In total, 126 women were recruited-82 in the nulliparous trial and 44 in the multiparous trial. Seven patients did not have external cephalic version before delivery but were included in the analysis of success of external cephalic version. One patient was lost to follow-up. The external cephalic version success rate for nulliparous patients was 24% (10 of 42) in patients who received nitroglycerin compared with 8% (3 of 40) in those who receive placebo (P=.04, one-sided Fisher exact test, odds ratio 3.85, lower bound 1.22). In multiparous patients, the external cephalic version success rate did not differ significantly between groups: 44% (10 of 23) in the nitroglycerin group compared with 43% (9 of 21) in the placebo group (P=.60). Treatment with intravenous nitroglycerin increased the rate of successful external cephalic version in nulliparous, but not in multiparous, women. Treatment with intravenous nitroglycerin appeared to be safe, but our numbers were too small to rule out rare serious adverse effects. I.

Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

PubMed

Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

2013-10-01

High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN administration was 3.2%. Discussion High-dose oral nitroglycerin administration is a practical alternative to IV nitroglycerin in the prehospital setting when administered by advanced providers. The prehospital protocol for high dose oral nitroglycerin was demonstrated to be safe in the cohort of patients studied. Limitations of the study include the relatively small sample size and the inability to identify hypotension that may have occurred following the cessation of data collection in the field. Hypotension was rare and self-limited in prehospital patients receiving MSN.

Effects of Nitroglycerin on Regional Myocardial Blood Flow in Coronary Artery Disease

PubMed Central

Horwitz, Lawrence D.; Gorlin, Richard; Taylor, Warren J.; Kemp, Harvey G.

1971-01-01

Regional myocardial blood flow before and after sublingual nitroglycerin was measured in 10 patients with coronary artery disease. During thoracotomy, 133Xe was injected directly into the subepicardium in diseased regions of the anterior left ventricular wall, and washout rates were recorded with a scintillation counter. All disappearance curves were closely approximated by two exponential decays analyzed as two parallel flow systems by the compartmental method. The appearance of a double exponential decay pattern in diseased regions suggests that the slow phase was associated with collateral blood flow, although nonhomogeneous myocardium-to-blood partition coefficients for xenon cannot be excluded. Nitroglycerin increased the rapid phase flow in 9 of 10 patients and the slow flow in 7 of 10 patients. Average flow increased in 9 of the 10 patients (P < 0.01). Mean rapid phase flow in the control state was 110 ml/100 g per min and after nitroglycerin increased to 132 ml/100 g per min (P < 0.01); slow phase flow increased from 12 ml/100 g per min to 15 ml/100 g per min (P < 0.05). It is concluded that, under these conditions, nitroglycerin improves perfusion in regions of diseased myocardium in patients with coronary artery disease. PMID:4999635

Nicorandil Versus Nitroglycerin for Symptomatic Relief of Angina in Patients With Slow Coronary Flow Phenomenon: A Randomized Clinical Trial.

PubMed

Sani, Hashem Danesh; Eshraghi, Ali; Nezafati, Mohammad Hassan; Vojdanparast, Mohammad; Shahri, Bahram; Nezafati, Pouya

2015-07-01

Patients with the coronary slow flow phenomenon frequently experience angina episodes. The present study aimed to compare the efficacy of nicorandil versus nitroglycerin for alleviation of angina symptoms in slow flow patients. In a single-center, single-blind, parallel-design, comparator-controlled, randomized clinical trial (NCT02254252), 54 patients with slow flow and normal or near-normal coronary angiography who presented with frequent angina episodes were randomly assigned to 1-month treatment with nicorandil 10 mg, 2 times a day (n = 27) or sustained-release glyceryltrinitrate 6.4 mg 2 times a day (n =27). Frequency of angina episodes, pain intensity, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were assessed at baseline and after 1 month of treatment. In all, 25 patients in the nicorandil arm and 24 patients in the nitroglycerin arm were analyzed. After 1 month, patients treated with nicorandil had fewer angina episodes (adjusted mean number of episodes per week, nicorandil versus nitroglycerin; 1.68 ± 0.15 vs 2.29 ± 0.15, P = .007, effect size = 14.6%). Patients also reported greater reductions in pain intensity with nicorandil versus nitroglycerin (adjusted mean of self-reported pain score; 3.03 ± 0.29 vs 3.89 ± 0.30, P = .046, effect size = 8.4%). A significantly higher proportion of patients in the nicorandil arm were categorized in CCS class I (76% vs 33.3%, P = .004) or class II (16.0% vs 45.8%, P = .032). In slow flow patients, nicorandil provides better symptomatic relief of angina than nitroglycerin. © The Author(s) 2015.

Correlation between algogenic effects of calcitonin-gene-related peptide (CGRP) and activation of trigeminal vascular system, in an in vivo experimental model of nitroglycerin-induced sensitization.

PubMed

Capuano, Alessandro; Greco, Maria Cristina; Navarra, Pierluigi; Tringali, Giuseppe

2014-10-05

The neural mechanism(s) underlying migraine remain poorly defined at present; preclinical and clinical studies show an involvement of CGRP in this disorder. However current evidence pointed out that CGRP does not exert an algogenic action per se, but it is able to mediate migraine pain only if the trigeminal-vascular system is sensitized. The present study was addressed to investigate CGRP-evoked behavior in nitric oxide (NO) sensitized rats, using an experimental model of nitroglycerin induced sensitization of trigeminal system, looking at neuropeptide release from different cerebral areas after the intra-peritoneal (i.p.) administration of NO-donors. CGRP injected into the rat whisker pad did not induce significant changes in face rubbing behavior compared to controls. On the contrary, CGRP injected in animals pre-treated with 10mg/kg nitroglycerin significantly increased the time spent in face rubbing. Nitroglycerin pre-treated animals did not show any rubbing behavior after locally injected saline. Furthermore, the i.p. treatment with nitroglycerin produced an increase of CGRP levels in brainstem and trigeminal ganglia, but not in the hypothalamus and hippocampus. The absolute amounts of CGRP produced in the brainstem were lower compared to those in the trigeminal ganglion; however, after nitroglycerin stimulation the percentage increase was higher in the brainstem. In conclusion, findings presented in this study suggest that CGRP induces a painful behavior in rats only after sensitization of trigeminal system; thus supporting the concept that a genetic as well as acquired predisposition to trigemino- vascular activation represents the neurobiological basis of CGRP nociceptive effects in migraineurs. Copyright © 2014 Elsevier B.V. All rights reserved.

A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial.

PubMed

Davidson, A; Veillard, A-S; Tognela, A; Chan, M M K; Hughes, B G M; Boyer, M; Briscoe, K; Begbie, S; Abdi, E; Crombie, C; Long, J; Boyce, A; Lewis, C R; Varma, S; Broad, A; Muljadi, N; Chinchen, S; Espinoza, D; Coskinas, X; Pavlakis, N; Millward, M; Stockler, M R

2015-11-01

We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Use of intra-arterial nitroglycerin during uterine artery embolization for severe postpartum hemorrhage with uterine artery vasospasm.

PubMed

Wang, Liangcheng; Horiuchi, Isao; Mikami, Yukiko; Takagi, Kenjiro; Okochi, Tomohisa; Hamamoto, Kohei; Chiba, Emiko; Matsuura, Katsuhiko

2015-04-01

Uterine artery embolization (UAE) is a standard method for treating postpartum hemorrhage (PPH), although uterine artery vasospasm during UAE may lead to failure of hemostasis. Here, we report our experience with a case of PPH in which the bleeding was successfully controlled by intra-arterial administration of nitroglycerin during the second UAE. A 30-year-old woman experienced PPH following a successful cesarean section, and a UAE was performed. However, 6 hours later, vaginal bleeding restarted; the reason for unsuccessful embolization during the first UAE was vasoconstriction due to hypovolemic shock. We performed a second UAE, but uterine bleeding continued. After intra-arterial administration of nitroglycerin, hemostasis was confirmed, and there was no reperfusion of the uterine artery. After these two UAE procedures, no recurrence of bleeding was observed. Thus, use of intra-arterial nitroglycerin was effective for controlling uterine artery vasospasm during UAE. However, larger studies are required to confirm these findings. Copyright © 2015. Published by Elsevier B.V.

In Vitro Anti-Candida Activity of Lidocaine and Nitroglycerin: Alone and Combined

PubMed Central

Palmeira-de-Oliveira, Ana; Ramos, Ana Rita; Gaspar, Carlos; Palmeira-de-Oliveira, Rita; Gouveia, Paula; Martinez-de-Oliveira, José

2012-01-01

The aim of this work was to study the anti-Candida activity of lidocaine and nitroglycerin alone and in combination. Ten Candida strains were included, corresponding to 1 collection type strain (ATCC 10231) and 9 clinical isolates: 4 C. albicans, 2 C. glabrata, 1 C. tropicalis, 1 C. krusei, and 1 C. parapsilosis. The CLSI reference M27-A3 micromethod was used to determine the anti-Candida activity of the drugs alone; minimal inhibitory and lethal concentrations were determined. The classic checkboard technique was used to determine the activity of combined drugs. Lidocaine fungicidal effect was dosedependent. Nitroglycerin exhibited a higher effect. The drugs combination resulted in a reduction of the inhibitory concentration, corresponding to an additive effect. In conclusion, both drugs exhibited an interesting anti-Candida activity. The combination of lidocaine with nitroglycerin was shown to have an additive effect against Candida spp., predicting the interest to include, in the future, these drugs in a new delivery system for the treatment of mucocutaneous candidosis. PMID:22675243

Impact of intravenous nitroglycerin in the management of acute decompensated heart failure.

PubMed

den Uil, Corstiaan A; Brugts, Jasper J

2015-02-01

Intravenous nitroglycerin is a well-known, but underused, treatment for acute decompensated heart failure. Nitroglycerin has a rapid onset of action and short half-life and there is a clear dose-response curve on both global hemodynamics and peripheral circulation. IV nitroglycerin reduces LV and RV filling pressures and afterload. In the case of acute decompensated heart failure, there is a typical decreased bioavailability of nitric oxide (NO), which needs to be supplemented by exogenous nitrates. Additionally, there is benefit on clinical endpoints, such as fast optimization of arterial oxygenation, lower rates of mechanical ventilation, and improved survival. Drawbacks of therapy include not only side effects such as headache, resistance, and development of tolerability to nitrates but also free radical production. However, nitrates in combination with diuretics remain the cornerstone of acute decompensated heart failure treatment. We propose a more aggressive use of nitrates and a more limited use of inotropes (due to ischemic demand and pro-arrhythmogenic characteristics) in normo- or hypertensive patients with acute heart failure.

Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway

PubMed Central

Mao, Mao; Sudhahar, Varadarajan; Ansenberger-Fricano, Kristine; Fernandes, Denise C.; Tanaka, Leonardo Y.; Fukai, Tohru; Laurindo, Francisco R.M.; Mason, Ronald P.; Vasquez-Vivar, Jeannette; Minshall, Richard D.; Stadler, Krisztian; Bonini, Marcelo G.

2012-01-01

Nitroglycerin (GTN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GTN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GTN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1–50 nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin-dependent accumulation of 3,4,5-InsP3, probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GTN pharmacological action at pharmacologically relevant doses. PMID:22037515

M‐Atrial Natriuretic Peptide and Nitroglycerin in a Canine Model of Experimental Acute Hypertensive Heart Failure: Differential Actions of 2 cGMP Activating Therapeutics

PubMed Central

McKie, Paul M.; Cataliotti, Alessandro; Ichiki, Tomoko; Sangaralingham, S. Jeson; Chen, Horng H.; Burnett, John C.

2014-01-01

Background Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M‐atrial natriuretic peptide (M‐ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator. Methods and Results HF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and following intravenous M‐ANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (MAP) was reduced by M‐ANP (139±4 to 118±3 mm Hg, P<0.05) and nitroglycerin (137±3 to 116±4 mm Hg, P<0.05); similar findings were recorded for pulmonary wedge pressure (PCWP) with M‐ANP (12±2 to 6±2 mm Hg, P<0.05) and nitroglycerin (12±1 to 6±1 mm Hg, P<0.05). M‐ANP enhanced renal function with significant increases (P<0.05) in glomerular filtration rate (38±4 to 53±5 mL/min), renal blood flow (132±18 to 236±23 mL/min), and natriuresis (11±4 to 689±37 mEq/min) and also inhibited aldosterone activation (32±3 to 23±2 ng/dL, P<0.05), whereas nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation. Conclusions Our results advance the differential cardiorenal actions of pGC (M‐ANP) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make M‐ANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal. PMID:24385449

M-atrial natriuretic peptide and nitroglycerin in a canine model of experimental acute hypertensive heart failure: differential actions of 2 cGMP activating therapeutics.

PubMed

McKie, Paul M; Cataliotti, Alessandro; Ichiki, Tomoko; Sangaralingham, S Jeson; Chen, Horng H; Burnett, John C

2014-01-02

Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M-atrial natriuretic peptide (M-ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator. HF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and following intravenous M-ANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (MAP) was reduced by M-ANP (139 ± 4 to 118 ± 3 mm Hg, P<0.05) and nitroglycerin (137 ± 3 to 116 ± 4 mm Hg, P<0.05); similar findings were recorded for pulmonary wedge pressure (PCWP) with M-ANP (12 ± 2 to 6 ± 2 mm Hg, P<0.05) and nitroglycerin (12 ± 1 to 6 ± 1 mm Hg, P<0.05). M-ANP enhanced renal function with significant increases (P<0.05) in glomerular filtration rate (38 ± 4 to 53 ± 5 mL/min), renal blood flow (132 ± 18 to 236 ± 23 mL/min), and natriuresis (11 ± 4 to 689 ± 37 mEq/min) and also inhibited aldosterone activation (32 ± 3 to 23 ± 2 ng/dL, P<0.05), whereas nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation. Our results advance the differential cardiorenal actions of pGC (M-ANP) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make M-ANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections

PubMed Central

Reitzel, Ruth A.; Hirsh-Ginsberg, Cheryl; Murray, Kimberly; Chaftari, Anne-Marie; Hachem, Ray; Raad, Issam

2016-01-01

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata. The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment. PMID:27297475

Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin

PubMed Central

Tahvanainen, Anna; Leskinen, Miia; Koskela, Jenni; Ilveskoski, Erkki; Alanko, Juha; Kähönen, Mika; Kööbi, Tiit; Lehtimäki, Lauri; Moilanen, Eeva; Mustonen, Jukka; Pörsti, Ilkka

2009-01-01

AIMS To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS Continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic blood pressure from fingers in the supine position and during head-up tilt were recorded in nine healthy subjects. Data were captured before and after L-arginine (10 mg mg−1 min−1) or saline infusion, salbutamol (400 µg) or placebo inhalation, and sublingual nitroglycerin (0.25 mg) or placebo resoriblet. RESULTS The results of all measurements were comparable before drug administration. The effects of inhaled salbutamol were apparent in the supine position: systemic vascular resistance (−9.2 ± 2.6%) and augmentation index (−4.0 ± 1.5%) decreased, and heart rate (8.6 ± 2.5%) and cardiac output (8.8 ± 3.1%) increased. L-arginine had no clear effects on supine haemodynamics, but during head-up tilt blood pressure was moderately decreased and reduction in aortic reflection time prevented, indicating improved large arterial compliance. Nitroglycerin reduced supine vascular resistance (−6.7 ± 1.8%) and augmentation index (−7.4 ± 1.6%), and increased cardiac output (+9.2 ± 2.7%). During head-up tilt, nitroglycerin increased cardiac output (+10.6 ± 5.6%) and heart rate (+40 ± 7.5%), decreased vascular resistance (−7.8 ± 5.8%) and augmentation index (−18.7 ± 3.2%), and prevented the decrease in aortic reflection time. CONCLUSIONS Inhaled salbutamol predominantly changed supine haemodynamics, whereas the moderate effects of L-arginine were observed during the head-up tilt. In contrast, small doses of nitroglycerin induced major changes in haemodynamics both supine and during the head-up tilt. Altogether, these results emphasize the importance of haemodynamic measurements in both the supine and upright positions. PMID:19660000

Valproate Attenuates Nitroglycerin-Induced Trigeminovascular Activation by Preserving Mitochondrial Function in a Rat Model of Migraine

PubMed Central

Li, Ruxian; Liu, Yushuang; Chen, Nan; Zhang, Yitong; Song, Ge; Zhang, Zhongling

2016-01-01

Background Migraine is a chronic disease that interferes with life quality and work productivity. Valproate shows protective effects against migraine, yet the underlying mechanisms are unclear. This study aimed to evaluate the potential effect of valproate on migraine using a rat model of nitroglycerin-induced trigeminovascular activation, as well as to explore the underlying mechanism. Material/Methods Intraperitoneal injection of nitroglycerin was conducted to induce trigeminovascular activation in rats. To explore the protective effect of valproate, a low dose (100 mg/kg) or a high dose (200 mg/kg) of valproate was intraperitoneally injected into rats, and then the levels of 5-hydroxytryptamine and nitric oxide in the peripheral blood were examined. The mtDNA copy number and the protein levels of peroxisome proliferator-activated receptor-γ coactivator 1α, mitochondrial transcription factor A, and peroxisome proliferator-activated receptor-γ in the spinal trigeminal nucleus were detected to evaluate the biogenesis of mitochondria. The mitochondrial energy metabolism was determined by the mitochondrial membrane potential and the levels of adenosine triphosphate, cytochrome C oxidase, and reactive oxygen species. Results Valproate attenuated nitroglycerin-induced trigeminovascular activation in rats, with reduced scratching behavior and restored 5-hydroxytryptamine and nitric oxide levels. Moreover, the mitochondrial energy metabolism and the biogenesis of mitochondria were preserved by valproate in nitroglycerin-treated rats. Conclusions The protective effect of valproate against migraine may be achieved through the modulation of mitochondrial biogenesis and function. Our study provides evidence for the potential use of valproate in the treatment of migraine. PMID:27618395

The effect of nitroglycerin on the IUD insertion experience in nulliparous women: a pilot study.

PubMed

Micks, Elizabeth A; Jensen, Jeffrey T; Bednarek, Paula H

2014-07-01

Concern about pain during placement of an intrauterine device (IUD) represents a barrier to use, especially among nulliparous women. We hypothesized that nitroglycerin gel applied vaginally 30 min prior to IUD placement would reduce insertion-related pain. We designed a randomized, double-blinded, placebo-controlled pilot study to evaluate the efficacy and tolerability of 0.5-mg nitroglycerin gel (1 mL) or identical placebo gel applied vaginally in nulliparous women 30 min prior to IUD placement. The study was limited to women who opted for the levonorgestrel-releasing intrauterine system. Subjects completed a series of 100-mm visual analogue scales at several time points. The primary outcome was subject-reported pain with passage of the IUD through the cervix. Secondary outcomes included subject-reported pain at other time points, provider-reported ease of insertion, side effects, adverse events and need for additional dilation. A total of 24 women were randomized. Baseline characteristics were similar between groups. The mean pain score with IUD deployment was 55.0 mm [standard deviation (SD) = 29.7 mm] in the placebo group and 57.4 mm (SD 22.1 mm) in the nitroglycerin group (p=.82). There was no difference in ease of insertion reported by providers. Two subjects required dilation, one in each group. Vaginal administration of 0.5-mg nitroglycerin gel 30 min prior to IUD placement does not appear to decrease patient-reported procedural pain among nulliparous women or ease of insertion for providers. Copyright © 2014 Elsevier Inc. All rights reserved.

[Effect of verapamil and nitroglycerin on transplanted lung function in canines].

PubMed

Jiang, Zhibin; Hu, Ping; Liu, Jianxin; Wang, Dianjun; Jin, Longyu; Hong, Chao

2014-08-01

To investigate the protective effect of combined administration of verapamil and nitroglycerin on the function of canine transplanted lungs. Twenty orthotopic left lung transplantations were performed in 40 canines, which were randomly divided into 4 groups. In group I (control), the donor lungs were perfused and preserved with LPD solution, while group II with LPD solution plus verapamil 0.1 g/L, group III with LPD solution plus nitroglycerin 0.1g/L, and group IV with LPD solution plus verapamil 0.1 g/L and nitroglycerin 0.1 g/L. Hemodynamics and graft gas exchange were assessed 0, 2 and 4 h after the operation. The lung grafts were harvested to measure the wet/dry weight ratio, malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity. Compared with group I, II and III, the mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), partial pressure of oxygen in arterial blood (PaO₂), dynamic compliance (Cdyn) and alveolar-arterial oxygen tension volume [P(A- a)O₂] in group IV were improved significantly (P<0.05). No significant difference in the partial pressure of carbondioxide (PaCO₂) and peak inspiratory pressure (PIP) was observed in the 4 groups (P>0.05). In group IV, the wet/dry weight ratio and MDA contents were lower than those in the other 3 groups, and the SOD activity was significantly higher than that of the other 3 groups (P<0.05). Verapamil and nitroglycerin in LPD solution can protect the respiratory function of canine lung grafts by attenuating pulmonary edema and oxidative stress.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.

PubMed

Reitzel, Ruth A; Rosenblatt, Joel; Hirsh-Ginsberg, Cheryl; Murray, Kimberly; Chaftari, Anne-Marie; Hachem, Ray; Raad, Issam

2016-09-01

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Valproate Attenuates Nitroglycerin-Induced Trigeminovascular Activation by Preserving Mitochondrial Function in a Rat Model of Migraine.

PubMed

Li, Ruxian; Liu, Yushuang; Chen, Nan; Zhang, Yitong; Song, Ge; Zhang, Zhongling

2016-09-12

BACKGROUND Migraine is a chronic disease that interferes with life quality and work productivity. Valproate shows protective effects against migraine, yet the underlying mechanisms are unclear. This study aimed to evaluate the potential effect of valproate on migraine using a rat model of nitroglycerin-induced trigeminovascular activation, as well as to explore the underlying mechanism. MATERIAL AND METHODS Intraperitoneal injection of nitroglycerin was conducted to induce trigeminovascular activation in rats. To explore the protective effect of valproate, a low dose (100 mg/kg) or a high dose (200 mg/kg) of valproate was intraperitoneally injected into rats, and then the levels of 5-hydroxytryptamine and nitric oxide in the peripheral blood were examined. The mtDNA copy number and the protein levels of peroxisome proliferator-activated receptor-γ coactivator 1α, mitochondrial transcription factor A, and peroxisome proliferator-activated receptor-γ in the spinal trigeminal nucleus were detected to evaluate the biogenesis of mitochondria. The mitochondrial energy metabolism was determined by the mitochondrial membrane potential and the levels of adenosine triphosphate, cytochrome C oxidase, and reactive oxygen species. RESULTS Valproate attenuated nitroglycerin-induced trigeminovascular activation in rats, with reduced scratching behavior and restored 5-hydroxytryptamine and nitric oxide levels. Moreover, the mitochondrial energy metabolism and the biogenesis of mitochondria were preserved by valproate in nitroglycerin-treated rats. CONCLUSIONS The protective effect of valproate against migraine may be achieved through the modulation of mitochondrial biogenesis and function. Our study provides evidence for the potential use of valproate in the treatment of migraine.

Atorvastatin Combined Nitroglycerin Therapy Confer Additive Effects on Rabbits with Dyslipidemia.

PubMed

Yang, Fang; Wang, Jindong; Li, Fei; Cui, Lei

2016-06-01

Endogenous nitric oxide (NO) is beneficial for inhibiting Rho-associated kinase 2 (ROCK2) expression. However, the effect of exogenous NO on ROCK2 expression is less investigated. Rabbits with dyslipidemia were produced and randomly assigned into untreated, atorvastatin, nitroglycerin and combined groups (n=10 in each group). Medication therapy was lasted for 2 weeks. Parameters of interest including lipid profiles, liver enzyme, C-reactive protein (CRP), malondialdehyde (MDA), NO level and ROCK2 level were assessed at baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medication treatment. No significant difference in parameters was found between groups at baseline. With 2 weeks of dyslipidemia establishment, as compared to baseline, serum levels of lipid profiles, CRP and MDA were profoundly elevated. In addition, reduced NO generation and enhanced ROCK2 expression were also observed. With 2 weeks of medication therapy, lipid profiles, systemic inflammation (reflected as serum CRP level) and oxidation (reflected as serum MDA level) were improved in the atorvastatin and combined groups but not in the nitroglycerin group (P<0.05). Furthermore, increased NO production in accompany with reduced ROCK2 expression were observed in both the atorvastatin and nitroglycerin groups, and these benefits were further enhanced by combined therapy (P<0.05). No liver enzymes elevation was observed after 2 weeks of medication therapy. Nitroglycerin-derived exogenous NO could effectively inhibit ROCK2 expression in rabbits with dyslipidemia which is independent of lipid-modification, and these efficacies could be enhanced by statins therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Intravenous nitroglycerin for controlled cord traction in the management of retained placenta.

PubMed

Visalyaputra, Shusee; Prechapanich, Japarath; Suwanvichai, Sukanya; Yimyam, Suwimol; Permpolprasert, Ladda; Suksopee, Pattipa

2011-02-01

To determine the effect of 200 μg of intravenous nitroglycerin in the release of retained placenta by controlled cord traction. In this randomized controlled study, 40 women with a placenta retained for 30 minutes received intravenously 200 μg of nitroglycerin or a normal saline solution before umbilical cord traction was initiated. The rates of successful removal of the retained placenta in the study (n=20) and control (n=20) groups were compared, as were blood pressure, pulse rate, blood loss, and adverse effects. The placenta was released in only 15% and 20% of the participants in the study and control group, respectively. The remainder of the participants required general anesthesia and manual removal of the retained placenta regardless of group assignation. Blood pressure fell in significantly more women in the study group, but there were no differences in estimated blood loss or minor adverse effects. Intravenously administered nitroglycerin did not facilitate the release of retained placenta by umbilical cord traction. However, cord traction may be performed longer than 30 minutes to attempt releasing the placenta before operative manual removal is initiated. Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

The Usefulness of 0.2% Topical Nitroglycerin for Chondrodermatitis Nodularis Helicis.

PubMed

Sanz-Motilva, V; Martorell-Calatayud, A; Gutiérrez García-Rodrigo, C; Hueso-Gabriel, L; García-Melgares, M L; Pelufo-Enguix, C; Alfaro-Rubio, A; Vanaclocha-Sebastián, F

2015-09-01

Chondrodermatitis nodularis helicis (CNH) is a painful idiopathic degenerative condition involving the skin and cartilage of the helix or antihelix of the ear. Topical nitroglycerin 2% is a relatively recent treatment option for CNH that has produced good results, although with adverse effects (17% of cases). The use of a lower concentration would probably achieve similar results with fewer adverse effects. The aim of this study was to evaluate the effectiveness and safety of topical nitroglycerin 0.2% in the treatment of CNH. We performed a retrospective observational study of patients treated in 2 Spanish hospitals between 2012 and 2014. The effectiveness of treatment was determined by clinical photography and assessment of symptoms using a verbal numerical rating scale. Of the 29 patients treated, 93% showed clinical improvement. In the group of responders, mean treatment duration was 1.8 months and mean follow-up was 5.9 months. Overall tolerance was good in all cases. Topical nitroglycerin 0.2% is an effective and well-tolerated conservative treatment option that improves the appearance of lesions and provides symptomatic relief in the majority of patients with CNH. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Two cases of Bezold-Jarisch reflex induced by intra-arterial nitroglycerin in critical left main coronary artery stenosis.

PubMed

Shah, Sachin P; Waxman, Sergio

2013-01-01

The Bezold-Jarisch reflex, a well-described phenomenon, occurs upon the stimulation of intracardiac mechanoreceptors and is mediated by vagal afferent nerve fibers. Several factors can sensitize the cardiovascular system to develop this reflex, including acute myocardial ischemia, natriuretic peptides, and, rarely, nitroglycerin administration in the setting of acute myocardial infarction. The development of the Bezold-Jarisch reflex in the presence of severe coronary artery stenosis, specifically left main coronary artery stenosis, has not been described. We report 2 cases of patients who underwent elective coronary angiography and were given intra-arterial nitroglycerin during radial sheath insertion to reduce radial artery spasm. In both patients, bradycardia and hypotension developed along with diaphoresis, consistent with the Bezold-Jarisch reflex. Coronary angiography revealed critical (>90%) left main coronary artery stenosis in both patients. Critical left main coronary artery stenosis might sensitize mechanoreceptors or vagal afferents to the development of the Bezold-Jarisch reflex after intra-arterial nitroglycerin use; however, the mechanism of this possible relationship is unclear. In addition to discussing our patients' cases, we review the medical literature relevant to the Bezold-Jarisch reflex.

The effects of sequential use of oxytocin and sublingual nitroglycerin in the cases of retained placenta.

PubMed

Kashanian, Maryam; Hasankhani, Samira; Sheikhansari, Narges; Bahasadri, Shohreh; Homam, Homa

2016-10-01

To evaluate the effects of adding sublingual nitroglycerin to oxytocin, for delivery of retained placenta after vaginal delivery. The study was performed as a placebo controlled clinical trial on women who did not finish delivering placenta after 30 min of active management of the third stage of labor. In case group, 1 mg nitroglycerin and in the control group, placebo was prescribed sublingually. In total, 80 women finished the study. The number of manual removal of placenta did not show significant difference between the two groups [25 women (62.5%) in the case and 30 women (75%) in the control group, p = 0.335]. There was no significant difference between the two groups according to duration of the third stage of labor, hemoglobin index, decline in HB index >30% and maternal vital signs after treatment. There was no significant difference between the two groups according to adverse effects [eight women (20%) in the case group and four (10%) in the control group (p = 0.348)]. The sequential use of oxytocin and sublingual nitroglycerin could not lead to delivery of more placentas and did not reduce the necessity of manual removal of placenta in comparison with placebo.

Ultra-Violet/Electron Beam Detoxification of Nitroglycerin/Propylene Glycol Dinrate Waste Water, Phase 1

DTIC Science & Technology

1994-03-16

University of Vienna’s Institute for Theoretical and Radiation Chemistry provided assistance in the development of chemical theory. Z. Liu, Associate...Professor of Applied Chemistry at the University of Science and Technology, Hefei, Peoples Republic of China provided support with physical measurements. The...include Glyocollic acid " Inogani Nitates> 90 nitroglycerine, propylene glycol dinitrate Inorganic Nitrates (PGDN), trimethylolethane trinitrate MDL

Lidocaine alleviates propofol related pain much better than metoprolol and nitroglycerin.

PubMed

Goktug, Asutay; Gulec, Handan; Takmaz, Suna Akin; Turkyilmaz, Esra; Basar, Hulya

2015-01-01

Injection pain after propofol administration is common and may disturb patients' comfort. The aim of this study was to compare effectiveness of intravenous (iv) nitroglycerin, lidocaine and metoprolol applied through the veins on the dorsum of hand or antecubital vein on eliminating propofol injection pain. There were 147 patients and they were grouped according to the analgesic administered. Metoprolol (n=31, Group M), lidocaine (n=32, Group L) and nitroglycerin (n=29, Group N) were applied through iv catheter at dorsum hand vein or antecubital vein. Pain was evaluated by 4 point scale (0 - no pain, 1 - light pain, 2 - mild pain, 3 - severe pain) in 5, 10, 15 and 20th seconds. ASA, BMI, patient demographics, education level and the effect of pathways for injection and location of operations were analyzed for their effect on total pain score. There were no differences between the groups in terms of total pain score (p=0.981). There were no differences in terms of total pain score depending on ASA, education level, location of operation. However, lidocaine was more effective when compared with metoprolol (p=0.015) and nitroglycerin (p=0.001) among groups. Although neither lidocaine nor metoprolol had any difference on pain management when applied from antecubital or dorsal hand vein (p>0.05), nitroglycerin injection from antecubital vein had demonstrated statistically lower pain scores (p=0.001). We found lidocaine to be the most effective analgesic in decreasing propofol related pain. We therefore suggest iv lidocaine for alleviating propofol related pain at operations. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Effects of subcutaneously infiltrated nitroglycerin on diameter, palpability, ease-of-puncture and pre-cannulation spasm of radial artery during transradial coronary angiography.

PubMed

Ezhumalai, Babu; Satheesh, Santhosh; Jayaraman, Balachander

2014-01-01

The success of transradial catheterization depends on meticulous access of radial artery which in turn depends on palpating a good radial pulse. Our objectives were to analyze the effects of subcutaneously infiltrated nitroglycerin on diameter of radial artery, palpability of radial pulse, ease-of-puncture and pre-cannulation spasm of radial artery during transradial coronary angiography. Patients undergoing transradial coronary angiography were randomized to Group NL or Group SL. In Group NL, 3 ml of solution containing nitroglycerin and lignocaine was infiltrated subcutaneously at the site intended for puncture of radial artery. Similarly, saline and lignocaine were infiltrated in Group SL. Diameter of radial artery was objectively assessed by ultrasonography. Measurements were performed at baseline and repeated at 1 min after injecting the solutions. The ease-of-puncture was evaluated by the number of punctures and the time needed for successful access of radial artery. Both groups had 100 patients each. Baseline diameter of radial artery was similar between two groups. The post-injection diameter of radial artery increased by 26.3% in Group NL and 11.4% in Group SL. Nitroglycerin significantly improved the palpability of radial pulse, reduced the number of punctures and shortened the time needed for successful access of radial artery. Pre-cannulation spasm of radial artery occurred in 1% of Group NL and 8% of Group SL. Subcutaneously infiltrated nitroglycerin leads to significant vasodilation of radial artery. This avoids pre-cannulation spasm of radial artery, enhances palpability of the radial pulse and thus makes the puncture of radial artery easier. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Effects of subcutaneously infiltrated nitroglycerin on diameter, palpability, ease-of-puncture and pre-cannulation spasm of radial artery during transradial coronary angiography

PubMed Central

Ezhumalai, Babu; Satheesh, Santhosh; Jayaraman, Balachander

2014-01-01

Background The success of transradial catheterization depends on meticulous access of radial artery which in turn depends on palpating a good radial pulse. Objectives Our objectives were to analyze the effects of subcutaneously infiltrated nitroglycerin on diameter of radial artery, palpability of radial pulse, ease-of-puncture and pre-cannulation spasm of radial artery during transradial coronary angiography. Methods Patients undergoing transradial coronary angiography were randomized to Group NL or Group SL. In Group NL, 3 ml of solution containing nitroglycerin and lignocaine was infiltrated subcutaneously at the site intended for puncture of radial artery. Similarly, saline and lignocaine were infiltrated in Group SL. Diameter of radial artery was objectively assessed by ultrasonography. Measurements were performed at baseline and repeated at 1 min after injecting the solutions. The ease-of-puncture was evaluated by the number of punctures and the time needed for successful access of radial artery. Results Both groups had 100 patients each. Baseline diameter of radial artery was similar between two groups. The post-injection diameter of radial artery increased by 26.3% in Group NL and 11.4% in Group SL. Nitroglycerin significantly improved the palpability of radial pulse, reduced the number of punctures and shortened the time needed for successful access of radial artery. Pre-cannulation spasm of radial artery occurred in 1% of Group NL and 8% of Group SL. Conclusions Subcutaneously infiltrated nitroglycerin leads to significant vasodilation of radial artery. This avoids pre-cannulation spasm of radial artery, enhances palpability of the radial pulse and thus makes the puncture of radial artery easier. PMID:25634390

Evaluation of the advantageous anesthetic properties of dexmedetomidine used as hypotensive agent compared with nitroglycerin in orthognathic surgery.

PubMed

Rummasak, Duangdee; Apipan, Benjamas

2014-12-01

To evaluate the advantageous anesthetic properties, such as the decrease of intraoperative analgesic requirement, time to extubation and recovery, and early postoperative pain, of dexmedetomidine used as hypotensive agent compared with nitroglycerin in orthognathic surgery. The authors implemented a prospective, single-blinded, randomized clinical trial. The sample was composed of healthy patients who were admitted for bimaxillary osteotomies and were assigned to 1 of 2 groups by a computer-generated random number and blinded to the group. Dexmedetomidine or nitroglycerin was used as the hypotensive drug for each group. All patients underwent hypotensive anesthesia and surgery according to standard protocol. Intraoperative amount of fentanyl, time to eye opening, time to follow basic verbal commands, time to extubation, early postoperative pain scores, and analgesics were recorded. Compared means were analyzed using the unpaired Student t test. A 2-sided statistical test was used. A P value less than .05 was considered significant. The sample was composed of 40 participants. The intraoperative fentanyl requirement was significantly lower in the dexmedetomidine group than in the nitroglycerin group (168.75±56.29 and 222.50±96.12 μg, respectively; P=.037). Times to eye opening and following commands were considerably longer in the dexmedetomidine group, but the time to extubation showed no meaningful difference. Early postoperative pain after 30 and 60 minutes and the requirement for meperidine were not meaningfully different between the 2 groups. Dexmedetomidine, used as a hypotensive drug, has anesthetic benefits compared with nitroglycerin. Dexmedetomidine decreases the intraoperative fentanyl requirement and does not meaningfully change the time to extubation, early postoperative pain, and analgesic drug requirement. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Post-procedural/pre-hemostasis intra-arterial nitroglycerin after transradial catheterization: A gender based analysis.

PubMed

Dharma, Surya; Kedev, Sasko; Patel, Tejas; Sukmawan, Renan; Gilchrist, Ian C; Rao, Sunil V

2016-01-01

We analyzed the effect of nitroglycerin on radial artery occlusion (RAO) in women undergoing transradial catheterization. A total of 1706 patients undergoing transradial catheterization were randomized to receive either 500μg intra-arterial nitroglycerin or placebo at the end of the radial procedure. We explored the gender-based analysis between women (n=539) and men (n=1167). The primary outcome was the incidence of RAO as confirmed by absence of antegrade flow at one day after the transradial procedure evaluated by duplex ultrasound of the radial artery. The use of nitroglycerin, as compared with placebo, did not significantly reduce the risk of RAO in women patients [odds ratio, 0.69; 95% confidence interval (CI), 0.38 to 1.26; P=0.147]. The risk of RAO was higher in women age <60years as compared with women age ≥60years [5.6% vs. 3.5%; odds ratio, 2.16; 95% CI, 1.18 to 3.94; P=0.008]. In women age <60years (n=237), both counter puncture technique and a duration of hemostasis ≥4h were associated with a similar enhanced risk of developing RAO (odds ratio, 3.51; 95% CI, 1.59 to 7.72; P<0.001). The administration of nitroglycerin at the end of a transradial catheterization in women did not reduce the risk of RAO as determined by ultrasound one day after the radial procedure. Age <60years was associated with a higher risk of RAO compared with age ≥60years in women. Further strategies to reduce RAO in women are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel approach to reduce radial artery occlusion after transradial catheterization: postprocedural/prehemostasis intra-arterial nitroglycerin.

PubMed

Dharma, Surya; Kedev, Sasko; Patel, Tejas; Kiemeneij, Ferdinand; Gilchrist, Ian C

2015-04-01

To evaluate whether administration of nitroglycerin through the sheath at the end of a transradial procedure might preserve the patency of the radial artery. Despite the increasing acceptance of transradial approach, radial artery occlusion (RAO) continues to be a vexing problem of transradial access and limits utility of the radial artery as an access site in the future. We conducted a multicenter, prospective, randomized, placebo-controlled, operator-blinded trial and enrolled 1,706 patients who underwent transradial catheterization in three experienced radial centers. Patients were randomized to receive either 500 µg nitroglycerin (n=853) or placebo (n=853), given intra-arterially through the sheath at the end of the radial procedure. The primary outcome was the incidence of RAO as confirmed by absence of antegrade flow at one day after the transradial procedure evaluated by duplex ultrasound of the radial artery. The use of nitroglycerin, as compared with placebo, reduced the risk of the primary outcome [8.3% vs. 11.7%; odds ratio, 0.62; 95% confidence interval (CI), 0.44-0.87; P=0.006]. From a multivariable analysis, duration of hemostasis was a predictor of RAO (odds ratio, (odds ratio, 3.11; 95% CI, 1.66 to 5.82; P<0.001). There were no significant differences between the groups with respect to the sheath size (P=0.311), number of puncture attempts (P=0.941), duration of hemostasis (P=0.379) and procedural time (P=0.095). The administration of nitroglycerin at the end of a transradial catheterization, reduced the incidence of RAO, examined 1 day after the radial procedure by ultrasound. Postprocedural/prehemostasis pharmacologic regimens may represent a novel target for further investigation to reduce RAO. © 2014 Wiley Periodicals, Inc.

Use of nitroglycerin by bolus prevents intensive care unit admission in patients with acute hypertensive heart failure.

PubMed

Wilson, Suprat Saely; Kwiatkowski, Gregory M; Millis, Scott R; Purakal, John D; Mahajan, Arushi P; Levy, Phillip D

2017-01-01

The purpose of this study was to compare health care resource utilization among patients who were given intravenous nitroglycerin for acute heart failure (AHF) in the emergency department (ED) by intermittent bolus, continuous infusion, or a combination of both. We retrospectively identified 395 patients that received nitroglycerin therapy in the ED for the treatment of AHF over a 5-year period. Patients that received intermittent bolus (n=124) were compared with continuous infusion therapy (n=182) and combination therapy of bolus and infusion (n=89). The primary outcomes were the frequency of intensive care unit (ICU) admission and hospital length of stay (LOS). On unadjusted analysis, rates of ICU admission were significantly lower in the bolus vs infusion and combination groups (48.4% vs 68.7% vs 83%, respectively; P<.0001) and median LOS (interquartile range) was shorter (3.7 [2.5-6.2 days]) compared with infusion (4.7 [2.9-7.1 days]) and combination (5.0 [2.9-6.7 days]) groups; P=.02. On adjusted regression models, the strong association between bolus nitroglycerin and reduced ICU admission rate remained, and hospital LOS was 1.9 days shorter compared with infusion therapy alone. Use of intubation (bolus [8.9%] vs infusion [8.8%] vs combination [16.9%]; P=.096) and bilevel positive airway pressure (bolus [26.6%] vs infusion [20.3%] vs combination [29.2%]; P=.21) were similar as was the incidence of hypotension, myocardial injury, and worsening renal function. In ED patients with AHF, intravenous nitroglycerin by intermittent bolus was associated with a lower ICU admission rate and a shorter hospital LOS compared with continuous infusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Ball Powder Production Wastewater Biodegradation Support Studies - With Nitroglycerine

DTIC Science & Technology

1989-02-01

in the wastewater. Characterization of the ball powder wastewater stream showed an actual average NG inlet concentration of 192 mg/L. Pilot test...the first phase of pilot testing, the recommendation was made to conduct an additional pilot test phase to determine the effect of nitroglycerin (NG...NG by aerobic bacteria, a pilot program was undertaken with the following objectives: 1) to determine the concentration of NG in the ball powder

Randomized, double-blind phase II study to compare nitroglycerin plus oral vinorelbine plus cisplatin with oral vinorelbine plus cisplatin alone in patients with stage IIIB/IV non-small cell lung cancer (NSCLC).

PubMed

Reinmuth, N; Meyer, A; Hartwigsen, D; Schaeper, C; Huebner, G; Skock-Lober, R; Bier, A; Gerecke, U; Held, C-P; Reck, M

2014-03-01

Adding nitroglycerin to the combination of vinorelbine plus cisplatin has been reported to improve the overall survival (OS) of Asian patients with stage IIIB/IV non-small cell lung cancer (NSCLC) probably due to better drug delivery based on changed vascular tonus. The main objective of our study was to evaluate the effect of adding nitroglycerin to vinorelbine and cisplatin in a Caucasian population. 66 chemonaïve patients with stage IIIB/IV NSCLC received oral vinorelbine (first cycle 60 mg/m(2), subsequent cycles: 80 mg/m(2) in the absence of any hematological toxicity ≥ grade 3 in cycle 1) once daily on days 1 and 8 of each cycle and cisplatin (80 mg/m(2) i.v.) on day 1 of each cycle (q3w). Nitroglycerin (arm A, n=34) or placebo patches (arm B, n=32) were administered once daily from day -3 to day 2 of each cycle and were removed about 12h after administration. One nitroglycerin patch contained 25mg nitroglycerin. Median age was 62.5 (33-82) years. In the overall population (n=66), the objective response rate (ORR) was 27.3% (all PR; 95%CI: 17.0-39.6), with a disease control rate (DCR) of 57.6% (95%CI: 44.8-69.7), a median time to progression (TTP) of 4.8 months (n=58; 95%CI: 3.4-5.9) and a median overall survival (OS) of 11.5 months (95%CI: 7.9-13.6). ORR and DCR were numerically higher in arm A than in arm B (35.3% vs. 18.8% and 61.8% vs. 53.1%, respectively), whereas TTP and OS were comparable. The main hematological and non-hematological toxicities grade ≥ 3 were moderate with no significant differences between the two treatment arms. Overall, oral vinorelbine plus cisplatin showed a high level of efficacy and adequate tolerability in first line treatment of NSCLC. Despite the low sample size per group the results seem to confirm the previous results reported in Asian patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Nitroglycerin can facilitate weaning of difficult-to-wean chronic obstructive pulmonary disease patients: a prospective interventional non-randomized study

PubMed Central

2010-01-01

Introduction Both experimental and clinical data give convincing evidence to acute cardiac dysfunction as the origin or a cofactor of weaning failure in patients with chronic obstructive pulmonary disease. Therefore, treatment targeting the cardiovascular system might help the heart to tolerate more effectively the critical period of weaning. This study aims to assess the hemodynamic, respiratory and clinical effects of nitroglycerin infusion in difficult-to-wean patients with severe chronic obstructive pulmonary disease. Methods Twelve difficult-to-wean (failed ≥ 3 consecutive trials) chronic obstructive pulmonary disease patients, who presented systemic arterial hypertension (systolic blood pressure ≥ 140mmHg) during weaning failure and had systemic and pulmonary artery catheters in place, participated in this prospective, interventional, non-randomized clinical trial. Patients were studied in two consecutive days, i.e., the first day without (Control day) and the second day with (Study day) nitroglycerin continuous intravenous infusion starting at the beginning of the spontaneous breathing trial, and titrated to maintain normal systolic blood pressure. Hemodynamic, oxygenation and respiratory measurements were performed on mechanical ventilation, and during a 2-hour T-piece spontaneous breathing trial. Primary endpoint was hemodynamic and respiratory effects of nitroglycerin infusion. Secondary endpoint was spontaneous breathing trial and extubation outcome. Results Compared to mechanical ventilation, mean systemic arterial pressure, rate-pressure product, mean pulmonary arterial pressure, and pulmonary artery occlusion pressure increased [from (mean ± SD) 94 ± 14, 13708 ± 3166, 29.9 ± 4.8, and 14.8 ± 3.8 to 109 ± 20mmHg, 19856 ± 4877mmHg b/min, 41.6 ± 5.8mmHg, and 23.4 ± 7.4 mmHg, respectively], and mixed venous oxygen saturation decreased (from 75.7 ± 3.5 to 69.3 ± 7.5%) during failing trials on Control day, whereas they did not change on Study day. Venous admixture increased throughout the trial on both Control day and Study day, but this increase was lower on Study day. Whereas weaning failed in all patients on Control day, nitroglycerin administration on Study day enabled a successful spontaneous breathing trial and extubation in 92% and 88% of patients, respectively. Conclusions In this clinical setting, nitroglycerin infusion can expedite the weaning by restoring weaning-induced cardiovascular compromise. PMID:21078149

Water Quality Criteria for Nitroglycerin.

DTIC Science & Technology

1986-07-01

in Bentley et al.’s (1978) algal bioassay with nitroglycerin, the lactose vehicle at a concentra- tion of 10 mg/L caused a 24 percent increase in cell...numbers of .j. canricornutum. Although lactose had also been used at concentrations of 1 and 100 mg/L, Bentley et al. corrected all cell counts for...this species by 24 percent regardless of the lactose concentration; thus they made no allowance for any lessening of this effect at lower vehicle con

Transdermal Nitroglycerin Delivery Using Acrylic Matrices: Design, Formulation, and In Vitro Characterization

PubMed Central

Ramazani Saadat Abadi, Ahmad

2014-01-01

Nitroglycerin (TNG) transdermal drug delivery systems (TDDSs) with different acrylic pressure-sensitive adhesives (PSAs) and chemical permeation enhancers (CPEs) were prepared. The effects of PSAs and CPEs types and concentrations on skin permeation and in vitro drug release from devices were evaluated using the dissolution method as well as the modified-jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that the permeation rate or steady state flux (J ss) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak 2516 and Duro-Tak 2054 showed the highest and Duro-Tak 2051 showed the lowest J ss. Among the various CPEs, propylene glycol and cetyl alcohol showed the highest and the lowest enhancement of the skin permeation of TNG, respectively. The adhesion properties of devices such as 180° peel strength and probe tack values were obtained. It was shown that increasing the concentration of CPE led to reduction in the adhesion property of PSA. Moreover, after optimization of the formulation, it was found that the use of 10% PG as a CPE and 25% nitroglycerin loading in Duro-Tak 2054 is an effective monolithic DIAP for the development of a transdermal therapeutic system for nitroglycerin. PMID:24511396

Cardio-ankle vascular index (CAVI) differentiates pharmacological properties of vasodilators nicardipine and nitroglycerin in anesthetized rabbits.

PubMed

Chiba, Tatsuo; Yamanaka, Mari; Takagi, Sachie; Shimizu, Kazuhiro; Takahashi, Mao; Shirai, Kohji; Takahara, Akira

2015-08-01

Cardio-ankle vascular index (CAVI) has been developed for measurement of vascular stiffness from the aorta to tibial artery, which is clinically utilized for assessing the progress of arteriosclerosis. In this study, we established measuring system of the CAVI in rabbits, and assessed whether the index could reflect different pharmacological actions of nitroglycerin and nicardipine on the systemic vasculature. Rabbits were anesthetized with halothane, and the CAVI was calculated from the well-established basic equations with variables obtained from brachial and tibial blood pressure and phonocardiogram. Nicardipine (1, 3 and 10 μg/kg, i.v.) decreased the blood pressure, femoral vascular resistance, and heart-ankle pulse wave velocity (haPWV). Meanwhile, no significant change was detected in the CAVI at the low or middle dose, which reflects the defining feature of the CAVI that is independent of blood pressure. The index increased at the high dose. Nitroglycerin (2, 4 and 8 μg/kg, i.v.) decreased the blood pressure, femoral vascular resistance, and haPWV. Meanwhile, the CAVI was decreased during the nitroglycerin infusion, which may reflect its well-known pharmacological action dilating conduit arteries. These results suggest that the CAVI differentiates the properties of these vasodilators in vivo. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The effect of nitroglycerin on microvascular perfusion and oxygenation during gastric tube reconstruction.

PubMed

Buise, Marc P; Ince, Can; Tilanus, Hugo W; Klein, Jan; Gommers, Diederik; van Bommel, Jasper

2005-04-01

Esophagectomy followed by gastric tube reconstruction is the surgical treatment of choice for patients with esophageal cancer. Complications of the cervical anastomosis are associated with impaired microvascular blood flow (MBF) and ischemia in the gastric fundus. The aim of the present study was to differentiate whether the decrease in MBF is a result of arterial insufficiency or of venous congestion. To do this we assessed MBF, microvascular hemoglobin oxygen saturation (muHbSo(2)), and microvascular hemoglobin concentration (muHbcon) simultaneously during different stages of gastric tube reconstruction. In 14 patients, MBF was determined with laser Doppler flowmetry, and muHbSo(2) and muHbcon were determined with reflectance spectro- photometry. After completion of the anastomosis, nitroglycerin was applied at the fundus. Although MBF did not change significantly in the pylorus, MBF decreased progressively during surgery in the fundus from 210 +/- 18 Arbitrary Units at baseline (normal stomach) to 52 +/- 9 Arbitrary Units after completion of reconstruction (mean +/- sem; P < 0.05). There was no change in muHbSo(2) and muHbcon during the reconstruction. After application of nitroglycerin, MBF doubled. We conclude that MBF decreases during gastric tube reconstruction but that muHbSo(2) and muHbcon do not. This decrease might be the result of venous congestion, which can partly be counteracted by application of nitroglycerin.

Transdermal Nitroglycerin Therapy May Not Prevent Early Postmenopausal Bone Loss

PubMed Central

Wimalawansa, Sunil J.; Grimes, Julia P.; Wilson, Alan C.; Hoover, Donald R.

2009-01-01

Context: Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss. Objective: The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss. Design: This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial. Setting: The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ). Participants: Participants included 186 postmenopausal women aged 40–65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to −2.5. Intervention: Women, stratified by lumbar T-score (<−1.50 and ≥−1.50) and years since menopause (≤5 and >5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements. Measurements: BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes. Results: After 36 months of therapy, changes of −2.1% in the active group (n = 88) and −2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval −1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P < 0.001). Other adverse and serious adverse events were not different. Conclusions: BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only ∼16 mg/d); a sub-therapeutic dose. PMID:19549739

Barrier Properties of Layered-Silicate Reinforced Ethylenepropylenediene Monomer/Chloroprene Rubber Nanorubbers.

PubMed

Wu, Chang Mou; Hsieh, Wen Yen; Cheng, Kuo Bin; Lai, Chiu-Chun; Lee, Kuei Chi

2018-05-09

The triacetin and nitroglycerin barrier properties of layered-silicate reinforced ethylenepropylenediene monomer/chloroprene rubber (EPDM/CR) nanorubbers were investigated as rocket-propellant inhibitors. EPDM/CR nanorubbers with intercalated structures were formulated and prepared by the melt-compounding method. The triacetin permeability and nitroglycerin absorption were observed to decrease with increasing layered-silicate content. The layered silicates also improved the flame retardancies of the nanorubbers by forming silicate reinforced carbonaceous chars. Layered-silicate reinforced EPDM/CR nanorubbers are potentially effective rocket propellant-inhibiting materials.

Topical Nitroglycerine for Neonatal Arterial Associated Peripheral Ischemia following Cannulation: A Case Report and Comprehensive Literature Review

PubMed Central

Mosalli, Rafat; Elbaz, Mohamed; Paes, Bosco

2013-01-01

Arterial cannulation in neonates is usually performed for frequent blood pressure monitoring and blood sampling. The procedure, while easily executed by skilled neonatal staff, can be associated with serious complications such as vasospasm, thrombosis, embolism, hematoma, infection, peripheral nerve damage, ischemia, and tissue necrosis. Several treatment options are available to reverse vascular induced ischemia and tissue damage. Applied interventions depend on the extent of tissue involvement and whether the condition is progressive and deemed life threatening. Standard, noninvasive measures include immediate catheter removal, limb elevation, and warming the contralateral extremity. Topical vasodilators, anticoagulation, thrombolysis, and surgery are considered secondary therapeutic strategies. A comprehensive literature search indicates that topical nitroglycerin has been utilized for the treatment of tissue ischemia in three preterms with umbilical arterial catheters and four with peripheral arterial lines. We report the first successful use of nitroglycerine ointment in a critically ill preterm infant with ischemic hand changes after brachial artery cannulation. PMID:24251058

Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

PubMed Central

Bossaller, C; Habib, G B; Yamamoto, H; Williams, C; Wells, S; Henry, P D

1987-01-01

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it. PMID:2432088

A Summary and Evaluation of Aquatic Environmental Data in Relation to Establishing Water Quality Criteria for Munitions-Unique Compounds. Part 2. Nitroglycerin.

DTIC Science & Technology

1979-04-01

AD-A082 437 WATER AND AIR RESEARCH INC GAINESVILLE FLA F/6 6/20 SUMMARY AND EVALUATION OF AQUATIC ENVIRONMENTAL DATA IN RELAT--ETC(U) APR 79 . H...ASummnary and Evaluation of Aquatic Environ- Final pt mental Data in Relation to Establishin Water 1 Ap 77 m.31 AugdW~I" j .H. Sullivan, Jr H. 0...effects of nitroglycerin (TNG) on the aquatic environment and to reconmmend water quality criteria for the protection of aquatic organisms. Chemical

Barrier Properties of Layered-Silicate Reinforced Ethylenepropylenediene Monomer/Chloroprene Rubber Nanorubbers

PubMed Central

Hsieh, Wen Yen; Cheng, Kuo Bin; Lai, Chiu-Chun; Lee, Kuei Chi

2018-01-01

The triacetin and nitroglycerin barrier properties of layered-silicate reinforced ethylenepropylenediene monomer/chloroprene rubber (EPDM/CR) nanorubbers were investigated as rocket-propellant inhibitors. EPDM/CR nanorubbers with intercalated structures were formulated and prepared by the melt-compounding method. The triacetin permeability and nitroglycerin absorption were observed to decrease with increasing layered-silicate content. The layered silicates also improved the flame retardancies of the nanorubbers by forming silicate reinforced carbonaceous chars. Layered-silicate reinforced EPDM/CR nanorubbers are potentially effective rocket propellant-inhibiting materials. PMID:29747427

Effects of intravenous bolus injection of nicorandil on renal artery flow velocity assessed by color Doppler ultrasound.

PubMed

Shimamoto, Yukiko; Kubo, Takashi; Tanabe, Kazumi; Emori, Hiroki; Katayama, Yosuke; Nishiguchi, Tsuyoshi; Taruya, Akira; Kameyama, Takeyoshi; Orii, Makoto; Yamano, Takashi; Kuroi, Akio; Yamaguchi, Tomoyuki; Takemoto, Kazushi; Matsuo, Yoshiki; Ino, Yasushi; Tanaka, Atsushi; Hozumi, Takeshi; Terada, Masaki; Akasaka, Takashi

2017-01-01

Previous animal studies have shown that a potassium channel opener, nicorandil, provokes vasodilation in renal microvasculature and increases renal blood flow. We conducted a clinical study that aimed to evaluate the effect of nicorandil on renal artery blood flow in comparison with nitroglycerin by using color Doppler ultrasound. The present study enrolled 40 patients with stable coronary artery disease who had no renal arterial stenosis and renal parenchymal disease. The patients received intravenous administration of nicorandil (n=20) or nitroglycerin (n=20). Before and after the administration, renal artery blood flow velocity was measured by color-guided pulsed-wave Doppler. The peak-systolic, end-diastolic, and mean renal artery blood flow velocities before the administration were not different between the nicorandil group and the nitroglycerin group. The peak-systolic (79±15cm/s to 99±21cm/s, p<0.001; and 78±19cm/s to 85±19cm/s, p=0.004), end-diastolic (22±5cm/s to 28±8cm/s, p<0.001; and 24±6cm/s to 26±6cm/s, p=0.005) and mean (41±6cm/s to 49±9cm/s, p<0.001; and 43±9cm/s to 45±9cm/s, p=0.009) renal artery flow velocities increased significantly in either group. The nominal changes in the peak-systolic (20±10cm/s vs. 7±8cm/s, p<0.001), end-diastolic (5±4cm/s vs. 2±3cm/s, p=0.001), and mean (8±5cm/s vs. 2±2cm/s, p<0.001) renal artery blood flow velocities were significantly greater in the nicorandil group compared with the nitroglycerin group. Intravenous nicorandil increased renal artery blood flow velocity in comparison with nitroglycerin. Nicorandil has a significant effect on renal hemodynamics. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Role of short-acting nitroglycerin in the management of ischemic heart disease.

PubMed

Boden, William E; Padala, Santosh K; Cabral, Katherine P; Buschmann, Ivo R; Sidhu, Mandeep S

2015-01-01

Nitroglycerin is the oldest and most commonly prescribed short-acting anti-anginal agent; however, despite its long history of therapeutic usage, patient and health care provider education regarding the clinical benefits of the short-acting formulations in patients with angina remains under-appreciated. Nitrates predominantly induce vasodilation in large capacitance blood vessels, increase epicardial coronary arterial diameter and coronary collateral blood flow, and impair platelet aggregation. The potential for the prophylactic effect of short-acting nitrates remains an under-appreciated part of optimal medical therapy to reduce angina and decrease myocardial ischemia, thereby enhancing the quality of life. Short-acting nitroglycerin, administered either as a sublingual tablet or spray, can complement anti-anginal therapy as part of optimal medical therapy in patients with refractory and recurrent angina either with or without myocardial revascularization, and is most commonly used to provide rapid therapeutic relief of acute recurrent angina attacks. When administered prophylactically, both formulations increase angina-free walking time on treadmill testing, abolish or delay ST segment depression, and increase exercise tolerance. The sublingual spray formulation provides several clinical advantages compared to tablet formulations, including a lower incidence of headache and superiority to the sublingual tablet in terms of therapeutic action and time to onset, while the magnitude and duration of vasodilatory action appears to be comparable. Furthermore, the sublingual spray formulation may be advantageous to tablet preparations in patients with dry mouth. This review discusses the efficacy and utility of short-acting nitroglycerin (sublingual spray and tablet) therapy for both preventing and aborting an acute angina attack, thereby leading to an improved quality of life.

Role of short-acting nitroglycerin in the management of ischemic heart disease

PubMed Central

Boden, William E; Padala, Santosh K; Cabral, Katherine P; Buschmann, Ivo R; Sidhu, Mandeep S

2015-01-01

Nitroglycerin is the oldest and most commonly prescribed short-acting anti-anginal agent; however, despite its long history of therapeutic usage, patient and health care provider education regarding the clinical benefits of the short-acting formulations in patients with angina remains under-appreciated. Nitrates predominantly induce vasodilation in large capacitance blood vessels, increase epicardial coronary arterial diameter and coronary collateral blood flow, and impair platelet aggregation. The potential for the prophylactic effect of short-acting nitrates remains an under-appreciated part of optimal medical therapy to reduce angina and decrease myocardial ischemia, thereby enhancing the quality of life. Short-acting nitroglycerin, administered either as a sublingual tablet or spray, can complement anti-anginal therapy as part of optimal medical therapy in patients with refractory and recurrent angina either with or without myocardial revascularization, and is most commonly used to provide rapid therapeutic relief of acute recurrent angina attacks. When administered prophylactically, both formulations increase angina-free walking time on treadmill testing, abolish or delay ST segment depression, and increase exercise tolerance. The sublingual spray formulation provides several clinical advantages compared to tablet formulations, including a lower incidence of headache and superiority to the sublingual tablet in terms of therapeutic action and time to onset, while the magnitude and duration of vasodilatory action appears to be comparable. Furthermore, the sublingual spray formulation may be advantageous to tablet preparations in patients with dry mouth. This review discusses the efficacy and utility of short-acting nitroglycerin (sublingual spray and tablet) therapy for both preventing and aborting an acute angina attack, thereby leading to an improved quality of life. PMID:26316714

Baicalin Alleviates Nitroglycerin-induced Migraine in Rats via the Trigeminovascular System.

PubMed

Sun, Yu-Yao; Zhang, Wen-Jun; Dong, Cui-Lan; Zhang, Xiao-Fan; Ji, Jun; Wang, Xue; Wang, Ling; Hu, Wan-Li; Du, Wen-Juan; Cui, Cheng-Long; Zhang, Chun-Feng; Li, Fei; Wang, Chong-Zhi; Yuan, Chun-Su

2017-06-01

Migraine is a common neurological disorder with a serious impact on quality of life. The aim of this study was to explore the effect of baicalin on nitroglycerin-induced migraine rats. We carried out a behavioral research within 2 h post-nitroglycerin injection, and blood samples were drawn for measurements of nitric oxide (NO), calcitonin gene-related peptide, and endothelin (ET) levels. Immunohistochemistry was adopted to detect the activation of C-fos immunoreactive neurons in periaqueductal gray. The number, area size, and integrated optical density of C-fos positive cells were measured using Image-Pro Plus. As a result, baicalin administration (0.22 mm/kg) alleviated pain responses of migraine rats. It profoundly decreased NO and calcitonin gene-related peptide levels, increased ET levels, and rebuilt the NO/ET balance in migraine rats. Besides, baicalin pretreatment significantly reduced the number, the stained area size, and integrated optical density value of C-fos positive cells. In brief, this paper supports the possibility of baicalin as a potential migraine pharmacotherapy. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Key Enzymes Enabling the Growth of Arthrobacter sp. Strain JBH1 with Nitroglycerin as the Sole Source of Carbon and Nitrogen

PubMed Central

Husserl, Johana; Hughes, Joseph B.

2012-01-01

Flavoprotein reductases that catalyze the transformation of nitroglycerin (NG) to dinitro- or mononitroglycerols enable bacteria containing such enzymes to use NG as the nitrogen source. The inability to use the resulting mononitroglycerols limits most strains to incomplete denitration of NG. Recently, Arthrobacter strain JBH1 was isolated for the ability to grow on NG as the sole source of carbon and nitrogen, but the enzymes and mechanisms involved were not established. Here, the enzymes that enable the Arthrobacter strain to incorporate NG into a productive pathway were identified. Enzyme assays indicated that the transformation of nitroglycerin to mononitroglycerol is NADPH dependent and that the subsequent transformation of mononitroglycerol is ATP dependent. Cloning and heterologous expression revealed that a flavoprotein catalyzes selective denitration of NG to 1-mononitroglycerol (1-MNG) and that 1-MNG is transformed to 1-nitro-3-phosphoglycerol by a glycerol kinase homolog. Phosphorylation of the nitroester intermediate enables the subsequent denitration of 1-MNG in a productive pathway that supports the growth of the isolate and mineralization of NG. PMID:22427495

Key enzymes enabling the growth of Arthrobacter sp. strain JBH1 with nitroglycerin as the sole source of carbon and nitrogen.

PubMed

Husserl, Johana; Hughes, Joseph B; Spain, Jim C

2012-05-01

Flavoprotein reductases that catalyze the transformation of nitroglycerin (NG) to dinitro- or mononitroglycerols enable bacteria containing such enzymes to use NG as the nitrogen source. The inability to use the resulting mononitroglycerols limits most strains to incomplete denitration of NG. Recently, Arthrobacter strain JBH1 was isolated for the ability to grow on NG as the sole source of carbon and nitrogen, but the enzymes and mechanisms involved were not established. Here, the enzymes that enable the Arthrobacter strain to incorporate NG into a productive pathway were identified. Enzyme assays indicated that the transformation of nitroglycerin to mononitroglycerol is NADPH dependent and that the subsequent transformation of mononitroglycerol is ATP dependent. Cloning and heterologous expression revealed that a flavoprotein catalyzes selective denitration of NG to 1-mononitroglycerol (1-MNG) and that 1-MNG is transformed to 1-nitro-3-phosphoglycerol by a glycerol kinase homolog. Phosphorylation of the nitroester intermediate enables the subsequent denitration of 1-MNG in a productive pathway that supports the growth of the isolate and mineralization of NG.

Cardiovascular effects of vasopressin following V(1) receptor blockade compared to effects of nitroglycerin.

PubMed

Cooke, C R; Wall, B M; Huch, K M; Mangold, T

2001-09-01

Studies to more clearly determine the mechanisms associated with arginine vasopressin (AVP)-induced vasodilation were performed in normal subjects and in quadriplegic subjects with impaired efferent sympathetic responses. Studies to compare the effects of AVP with the hemodynamic effects of nitroglycerin, an agent that primarily affects venous capacitance vessels, were also performed in normal subjects. Incremental infusions of AVP following V(1)-receptor blockade resulted in equivalent reductions in systemic vascular resistance (SVRI) in normal and in quadriplegic subjects. However, there were major differences in the effect on mean arterial pressure (MAP), which was reduced in quadriplegic subjects but did not change in normal subjects. This difference in MAP can be attributed to a difference in the magnitude of increase in cardiac output (CI), which was twofold greater in normal than in quadriplegic subjects. These observations are consistent with AVP-induced vasodilation of arterial resistance vessels with reflex sympathetic enhancement of CI and are clearly different from the hemodynamic effects of nitroglycerin, i.e., reductions in MAP, CI, and indexes of cardiac preload, with only minor changes in SVRI.

Comparison of sublingual tablets with nitroglycerin complexed with beta-cyclodextrin or titrated with crosspovidone--technological approach.

PubMed

Centkowska, Katarzyna; Sznitowska, Małgorzata

2008-01-01

Fast disintegrating sublingual tablets containing nitroglycerin either complexed with beta-cyclodextrin (NTG-CD) or titrated with crosspovidone (NTG-CP) were prepared using Starch 1500 or StarLac as disintegrants. Regarding disintegration time and stability of the active substance Starch 1500 was more appropriate for NTG-CD while for NTG-CP StarLac was suitable. Stability of NTG was better in NTG-CD tablets than in NTG-CP tablets, however, within 12 months of storage at 25 degrees C the loss of NTG in all formulations was still greater than 10%.

A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients.

PubMed

Chaftari, Anne-Marie; Hachem, Ray; Szvalb, Ariel; Taremi, Mahnaz; Granwehr, Bruno; Viola, George Michael; Sapna, Amin; Assaf, Andrew; Numan, Yazan; Shah, Pankil; Gasitashvili, Ketevan; Natividad, Elizabeth; Jiang, Ying; Slack, Rebecca; Reitzel, Ruth; Rosenblatt, Joel; Mouhayar, Elie; Raad, Issam

2017-07-01

For long-term central lines (CL), the lumen is the major source of central line-associated bloodstream infections (CLABSI). The current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore, heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel nonantibiotic catheter lock solution for the prevention of CLABSI. Between November 2015 and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheters (PICC) to receive the study lock solution. The study lock consisted of 15 or 30 μg/ml of nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen was locked for at least 2 h once daily prior to being flushed. After enrollment of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the dose was escalated to the higher dose (30 μg/ml). There were no serious related adverse events or episodes of hypotension with lock administration. Two patients experienced mild transient adverse events (one headache and one rash) possibly related to the lock and that resolved without residual effect. The CLABSI rate was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis, compared with a rate of 1.9/1,000 CD at the institution in the same patient population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and well tolerated. It may prevent CLABSI when given daily to cancer patients. Large, prospective, randomized clinical trials are needed to validate these findings. (This study has been registered at ClinicalTrials.gov under identifier NCT02577718.). Copyright © 2017 American Society for Microbiology.

A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients

PubMed Central

Hachem, Ray; Szvalb, Ariel; Taremi, Mahnaz; Granwehr, Bruno; Viola, George Michael; Sapna, Amin; Assaf, Andrew; Numan, Yazan; Shah, Pankil; Gasitashvili, Ketevan; Natividad, Elizabeth; Jiang, Ying; Slack, Rebecca; Reitzel, Ruth; Rosenblatt, Joel; Mouhayar, Elie; Raad, Issam

2017-01-01

ABSTRACT For long-term central lines (CL), the lumen is the major source of central line-associated bloodstream infections (CLABSI). The current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore, heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel nonantibiotic catheter lock solution for the prevention of CLABSI. Between November 2015 and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheters (PICC) to receive the study lock solution. The study lock consisted of 15 or 30 μg/ml of nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen was locked for at least 2 h once daily prior to being flushed. After enrollment of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the dose was escalated to the higher dose (30 μg/ml). There were no serious related adverse events or episodes of hypotension with lock administration. Two patients experienced mild transient adverse events (one headache and one rash) possibly related to the lock and that resolved without residual effect. The CLABSI rate was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis, compared with a rate of 1.9/1,000 CD at the institution in the same patient population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and well tolerated. It may prevent CLABSI when given daily to cancer patients. Large, prospective, randomized clinical trials are needed to validate these findings. (This study has been registered at ClinicalTrials.gov under identifier NCT02577718.) PMID:28416559

Clonidine versus nitroglycerin infusion in laparoscopic cholecystectomy.

PubMed

Mishra, Manjaree; Mishra, Shashi Prakash; Mathur, Sharad Kumar

2014-01-01

Laparoscopic surgery offers the advantages of minimally invasive surgery; however, pneumoperitoneum and the patient's position induce pathophysiological changes that may complicate anesthetic management. We studied the effect of clonidine and nitroglycerin on heart rate and blood pressure, if any, in association with these drugs or the procedure, as well as the effect of these drugs, if any, on end-tidal carbon dioxide pressure and intraocular pressure. Sixty patients (minimum age of 20 years and maximum age of 65 years, American Society of Anesthesiologists class I or II) undergoing laparoscopic cholecystectomy were randomized into 3 groups and given an infusion of clonidine (group I), nitroglycerin (group II), or normal saline solution (group III) after induction and before creation of pneumoperitoneum. We observed and recorded the following parameters: heart rate, mean arterial blood pressure, end-tidal carbon dioxide pressure, and intraocular pressure. The mean and standard deviation of the parameters studied during the observation period were calculated for the 3 treatment groups and compared by use of analysis of variance tests. Intragroup comparison was performed with the paired t test. The critical value of P, indicating the probability of a significant difference, was taken as < .05 for comparisons. Statistically significant differences in heart rate were observed among the various groups, whereas comparisons of mean arterial pressure, intraocular pressure, and end-tidal carbon dioxide pressure showed statistically significant differences only between groups I and III and between groups II and III. We found clonidine to be more effective than nitroglycerin at preventing changes in hemodynamic parameters and intraocular pressure induced by carbon dioxide insufflation during laparoscopic cholecystectomy. It was also found not to cause hypotension severe enough to stop the infusion and warrant treatment.

Clonidine Versus Nitroglycerin Infusion in Laparoscopic Cholecystectomy

PubMed Central

Mishra, Manjaree; Mishra, Shashi Prakash

2014-01-01

Background and Objectives: Laparoscopic surgery offers the advantages of minimally invasive surgery; however, pneumoperitoneum and the patient's position induce pathophysiological changes that may complicate anesthetic management. We studied the effect of clonidine and nitroglycerin on heart rate and blood pressure, if any, in association with these drugs or the procedure, as well as the effect of these drugs, if any, on end-tidal carbon dioxide pressure and intraocular pressure. Methods: Sixty patients (minimum age of 20 years and maximum age of 65 years, American Society of Anesthesiologists class I or II) undergoing laparoscopic cholecystectomy were randomized into 3 groups and given an infusion of clonidine (group I), nitroglycerin (group II), or normal saline solution (group III) after induction and before creation of pneumoperitoneum. We observed and recorded the following parameters: heart rate, mean arterial blood pressure, end-tidal carbon dioxide pressure, and intraocular pressure. The mean and standard deviation of the parameters studied during the observation period were calculated for the 3 treatment groups and compared by use of analysis of variance tests. Intragroup comparison was performed with the paired t test. The critical value of P, indicating the probability of a significant difference, was taken as < .05 for comparisons. Results: Statistically significant differences in heart rate were observed among the various groups, whereas comparisons of mean arterial pressure, intraocular pressure, and end-tidal carbon dioxide pressure showed statistically significant differences only between groups I and III and between groups II and III. Conclusion: We found clonidine to be more effective than nitroglycerin at preventing changes in hemodynamic parameters and intraocular pressure induced by carbon dioxide insufflation during laparoscopic cholecystectomy. It was also found not to cause hypotension severe enough to stop the infusion and warrant treatment. PMID:25392635

Effect of the addition of vasopressin or vasopressin plus nitroglycerin to epinephrine on arterial blood pressure during cardiopulmonary resuscitation in humans.

PubMed

Ducros, Laurent; Vicaut, Eric; Soleil, Christian; Le Guen, Morgan; Gueye, Papa; Poussant, Thomas; Mebazaa, Alexandre; Payen, Didier; Plaisance, Patrick

2011-11-01

Infusion of a vasopressor during cardiopulmonary resuscitation (CPR) in humans increases end decompression (diastolic) arterial blood pressure, and consequently increases vital organ perfusion pressure and survival. Several vasoactive drugs have been tested alone or in combination, but their hemodynamic effects have not been investigated clinically in humans. We tested the hypothesis that epinephrine (1 mg) co-administered with vasopressin (40 IU) ± nitroglycerin (300 μg) results in higher diastolic blood pressure than epinephrine alone. A prospective, randomized, double-blinded controlled trial in the prehospital setting. The study included 48 patients with witnessed cardiac arrest. Patients received either epinephrine alone (E alone) or epinephrine plus vasopressin (E+V) or epinephrine plus vasopressin plus nitroglycerin (E+V+N). A femoral arterial catheter was inserted for arterial pressure measurement. The primary end point was diastolic blood pressure during CPR, 15 min after the first drug administration (T = 15 min). After exclusions, a total of 44 patients were enrolled. Diastolic blood pressures (mm Hg) at T = 15 min were not statistically different between groups (median [interquartile range]: 20 [10], 15 [6], and 15 [13] for E alone, E+V, and E+V+N, respectively. The rate of return of spontaneous circulation was 63% (n = 10) in the epinephrine group, 43% (n = 6) in the epinephrine plus vasopressin group, and 36% (n = 5) in the triple therapy group (NS). Addition of vasopressin or vasopressin plus nitroglycerin to epinephrine did not increase perfusion blood pressure compared to epinephrine alone in humans in cardiac arrest, suggesting the absence of benefit in using these drug combination(s). Copyright © 2011 Elsevier Inc. All rights reserved.

Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans.

PubMed

Diaz, K M; Veerabhadrappa, P; Kashem, M A; Thakkar, S R; Feairheller, D L; Sturgeon, K M; Ling, C; Williamson, S T; Kretzschmar, J; Lee, H; Grimm, H; Babbitt, D M; Vin, C; Fan, X; Crabbe, D L; Brown, M D

2013-11-01

The purpose of this study was to investigate the association of visit-to-visit and 24-h blood pressure (BP) variability with markers of endothelial injury and vascular function. We recruited 72 African Americans who were non-diabetic, non-smoking and free of cardiovascular (CV) and renal disease. Office BP was measured at three visits and 24-h ambulatory BP monitoring was conducted to measure visit-to-visit and 24-h BP variability, respectively. The 5-min time-course of brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were assessed as measures of endothelial and smooth muscle function. Fasted blood samples were analyzed for circulating endothelial microparticles (EMPs). Significantly lower CD31+CD42- EMPs were found in participants with high visit-to-visit systolic blood pressure (SBP) variability or high 24-h diastolic blood pressure (DBP) variability. Participants with high visit-to-visit DBP variability had significantly lower flow-mediated dilation and higher nitroglycerin-mediated dilation at multiple time-points. When analyzed as continuous variables, 24-h mean arterial pressure variability was inversely associated with CD62+ EMPs; visit-to-visit DBP variability was inversely associated with flow-mediated dilation normalized by smooth muscle function and was positively associated with nitroglycerin-mediated dilation; and 24-h DBP variability was positively associated with nitroglycerin-mediated dilation. All associations were independent of age, gender, body mass index and mean BP. In conclusion, in this cohort of African Americans visit-to-visit and 24-h BP variability were associated with measures of endothelial injury, endothelial function and smooth muscle function. These results suggest that BP variability may influence the pathogenesis of CV disease, in part, through influences on vascular health.

Effects of nitroglycerin and ethylene glycol dinitrate mixture (blasting oil) on rat brain, liver and kidney.

PubMed

Zitting, A; Savolainen, H

1982-07-01

Rats were injected intraperitoneally (150 mg/kg) with a mixture of nitroglycerin and ethylene glycol dinitrate (1:3). Treatment caused a transient small increase in methemoglobin contents in blood and diminished contents of reduced glutathione in liver and brain. Hepatic cytochrome P-450 concentration and ethoxycoumarin deethylase activity decreased shortly after exposure but later the effect disappeared. Succinate dehydrogenase activity decreased in liver, kidney and brain. In brain, activity of creatine kinase increased significantly and slight increase in hepatic UDPglucuronosyltransferase and epoxide hydrolase activity was observed. Renal ethoxycoumarin activity increased transiently. The results point to interaction of hydrolytically released nitrite with hemoproteins.

The effects of nitroglycerin, norepinephrine and aminophylline on intrapulmonary arteriovenous anastomoses in healthy humans at rest.

PubMed

Lozo, Mislav; Lojpur, Mihajlo; Madden, Dennis; Lozo, Petar; Banic, Ivana; Dujic, Zeljko

2014-08-01

We have investigated the effects of the intravenous infusion of nitroglycerin (NTG), norepinephrine (NE) and aminophylline (AMP) on the opening and recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) in healthy humans at rest. In ten volunteers saline contrast echocardiography was performed during administration of two doses of the NTG (3μgkg(-1)min(-1) and 6μgkg(-1)min(-1)) and NE (0.1μgkg(-1)min(-1) and 0.25μgkg(-1)min(-1)) as well as 30min following the administration of AMP at rate of 6mgkg(-1). Echocardiography was used to assign bubble scores (0-5) based on the number and spatial distribution of bubbles in the left ventricle. Doppler ultrasound was used to estimate pulmonary artery systolic pressure. Using a Finometer the following hemodynamic parameters were assessed: heart rate, stroke volume, cardiac output, total peripheral resistance as well as systolic, diastolic and mean arterial pressure. The most important finding from the current study was that nitroglycerin, norepinephrine and aminophylline in the applied doses were not found to promote IPAVA opening in healthy humans at rest. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of nitroglycerin and glucagon administration on selective common bile duct cannulation and prevention of post-ERCP pancreatitis.

PubMed

Katsinelos, Panagiotis; Lazaraki, Georgia; Chatzimavroudis, Grigoris; Katsinelos, Taxiarchis; Georgakis, Nikos; Anastasiadou, Kyriaki; Gatopoulou, Anthi; Zeglinas, Christos; Psarras, Kyriakos; Kountouras, Jannis

2017-01-01

Easy common bile duct (CBD) cannulation is associated with low complication rate. This study aimed to investigate the potential impact of nitroglycerin and glucagon administration on selective CBD cannulation and prevention of post-ERCP pancreatitis. A prospective single center, double-blind randomized study in which a total of 455 patients were randomly assigned to CBD cannulation by receiving 6 puffs (2.4 mg) sublingual nitroglycerin and glucagon 1 mg intravenously (n = 227, group A) or 6 puffs sterile water and 20 mg hyoscine-n-butyl bromide intravenously (n = 228, group B). After ERCP, patients were followed for the development of drugs' side-effects and post-ERCP complications. There were no statistically significant differences between the two groups regarding demographic data and ERCP findings. Success rate of selective CΒD cannulation was 95.15% in group A versus 82.29% in group B (p < .001). Time required for CBD cannulation was 2.82 ± 2.31 min in group A versus 4.27 ± 3.84 min in group B (p = .021). Needle-knife papillotomy was used in 11 (4.85%) patients of group A and 39 (17.11%) patients of group B (p = .001). The frequency of post-ERCP pancreatitis was significantly lower in group A than in group B (3.08% versus 7.46%, p = .037). No difference was observed between the two groups with regard to the occurrence of post-procedure hemorrhage. There was no procedure-related mortality; no adverse event related to the combination regimen was observed. Combined nitroglycerin and glucagon administration achieves a high selective CBC cannulation rates with concomitant reduction of post-ERCP pancreatitis incidence. However, further relative large-scale studies are needed to confirm our findings before definite conclusions can be drawn (Clinical trial registration number: NT: 4321).

Effect of placental tissue on inhibition of uterine contraction by nitric oxide donors.

PubMed

Syal, A; Okawa, T; Vedernikov, Y; Chwalisz, K; Saade, G R; Garfield, R E

1999-08-01

Our purpose was to test the hypothesis that placental tissue modulates the effect of nitric oxide on spontaneous uterine contractility in pregnant rats. Rings (approximately 4 mm) of uterus taken from rats on day 14 (midpregnancy, n = 6), day 18 (late pregnancy, n = 4), and day 22 (term, n = 4) of gestation were placed in organ chambers filled with Krebs-bicarbonate buffer bubbled with 5% carbon dioxide in air (37 degrees C, pH approximately 7.4) for isometric tension recording. In some rings a piece of placenta was left attached to the uterine wall. In the other rings the fetuses, placentas, and membranes were removed completely. Change of spontaneous contractions of the rings (percentage change of basal integral activity for 10 minutes) in response to cumulative concentrations of the nitric oxide donors diethylamine-nitric oxide and nitroglycerin (10(-6) mol/L to 10(-4) mol/L) were compared between rings with and without placenta. Diethylamine-nitric oxide and nitroglycerin inhibited spontaneous uterine contractions in rings from midpregnancy, in both the absence and the presence of placenta. In rings from midpregnancy, the maximal inhibition of contractions by diethylamine-nitric oxide but not by nitroglycerin was significantly (P <.05) higher in the presence (26.7% +/- 3.5% of basal activity) than in the absence (39. 6% +/- 3.3%) of placenta. Inhibition of contraction by nitric oxide donors in rings from late and term pregnancy was less than in midpregnancy, and the presence of placental tissue did not influence the responses. The presence of placental tissue enhances inhibition of uterine contractility by agents that spontaneously release nitric oxide, such as diethylamine-nitric oxide, but not by nitroglycerin, which requires metabolic transformation for nitric oxide to be released. Refractoriness to nitric oxide near or at term does not depend on the presence or absence of placental tissue.

Internal sphincterotomy versus topical nitroglycerin ointment for chronic anal fissure.

PubMed

Aslam, Muhammad I; Pervaiz, Arif; Figueiredo, Rodrigo

2014-01-01

Anal fissure is a common benign condition. An anorectal problem is defined as a split in the anal canal mucosa that extends from the dentate line to the anal verge. Chronic anal fissure is defined by a history of symptoms present for more than 2 months' duration and with a triad of external skin tags, namely, a hypertrophied anal papilla, an ulcer with rolled edges, and a base exposing the internal sphincter. Because complications such as incontinence are associated with surgical treatment, chemical sphincterotomy is currently favored. The objective of this study is to compare the difference in outcome between open partial lateral anal sphincterotomy and application of topical 0.2% nitroglycerin ointment for the treatment of chronic anal fissure. This was a quasi-experimental study carried out between January 16, 2007 and January 15, 2008 in the Surgical Department of Jinnah Hospital, Lahore, Pakistan. Sixty consecutive cases with a clinical diagnosis of chronic anal fissure were recruited in the study. All recruited patients met the study inclusion criteria and were randomly assigned to one of the two groups. Group A was managed conservatively using topical 0.2% nitroglycerin ointment, whereas Group B underwent open partial lateral anal sphincterotomy. Both groups were followed up at 1 week, 2 weeks, 4 weeks, and 6 weeks after the treatment. All the patients complained of pain. A total of 43 (71.7%) patients had pain with constipation, whereas 31 (51.7%) patients had bleeding per rectum. Upon clinically examining the anal area, tenderness was elicited in all 60 (100%) patients. Group A included 30 (11 females and 19 males) cases treated with topical 0.2% nitroglycerin ointment and Group B included 30 (11 females and 19 males) cases who underwent open partial lateral anal sphincterotomy. In Group A, only 15 patients with fissures were successfully treated (50%). By contrast, 28 (93%) patients with fissures in Group B were successfully treated, and only two (7%) remained uncured. These two patients (6.6%) in Group B suffered from incontinence due to flatus and feces as a complication of the procedure. This quasi-experimental study demonstrates that open partial lateral internal sphincterotomy is superior to topical 0.2% nitroglycerin application in the treatment of chronic anal fissure, with good symptomatic relief, high rate of healing, fewer side effects, and a very low rate of early continence disturbances. Copyright © 2013. Published by Elsevier B.V.

High-sensitivity detection of TNT

PubMed Central

Pushkarsky, Michael B.; Dunayevskiy, Ilya G.; Prasanna, Manu; Tsekoun, Alexei G.; Go, Rowel; Patel, C. Kumar N.

2006-01-01

We report high-sensitivity detection of 2,4,6-trinitrotoluene (TNT) by using laser photoacoustic spectroscopy where the laser radiation is obtained from a continuous-wave room temperature high-power quantum cascade laser in an external grating cavity geometry. The external grating cavity quantum cascade laser is continuously tunable over ≈400 nm around 7.3 μm and produces a maximum continuous-wave power of ≈200 mW. The IR spectroscopic signature of TNT is sufficiently different from that of nitroglycerine so that unambiguous detection of TNT without false positives from traces of nitroglycerine is possible. We also report the results of spectroscopy of acetylene in the 7.3-μm region to demonstrate continuous tunability of the IR source. PMID:17164325

Avanafil

MedlinePlus

... taking or have recently taken riociguat (Adempas) or nitrates such as isosorbide dinitrate (Dilatrate-SR, Isordil, in ... and nitroglycerin (Minitran, Nitro-Dur, Nitromist, Nitrostat, others). Nitrates come as tablets, sublingual (under the tongue) tablets, ...

Nitroglycerin Topical

MedlinePlus

... place and cover it with a piece of plastic kitchen wrap to prevent the ointment from staining ... to apply the medication. Cover your finger with plastic wrap, a disposable surgical glove, or a finger ...

30 CFR 77.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... black powder, dynamite, nitroglycerin, fulminate, ammonium nitrate when mixed with a hydrocarbon, and...; (d) Berm means a pile or mound of material capable of restraining a vehicle; (e) Blasting agent means...

Nitroglycerin Transdermal Patch

MedlinePlus

... vasodilators. It works by relaxing the blood vessels so that the heart does not need to work ... patches may be applied in slightly different ways, so be sure to follow the directions included with ...

Which hemodynamic parameter predicts nitroglycerin-potentiated head-up tilt test response?

PubMed

Russo, Vincenzo; Papa, Andrea Antonio; Ciardiello, Carmine; Rago, Anna; Proietti, Riccardo; Calabrò, Paolo; Russo, Maria Giovanna; Nigro, Gerardo

2015-04-01

The aim of our study was to identify the early hemodynamic predictors of head-up tilt test (HUTT) outcome in healthy patients with recurrent unexplained syncope. The study involved 95 patients (mean age 38 ± 15; 42 male) who were referred for the evaluation of the syncopal episodes from October 2012 to May 2013. According to the nitroglycerin-potentiated diagnostic tilt test response, the study population was divided into two groups: HUTT+ Group (61 patients, mean age 37 ± 10; 27 male) and HUTT- Group (34 patients, mean age 38 ± 11; 15 male) with no tilt-induced syncope. Finger arterial blood pressure (BP) was recorded during tilt testing. Left ventricular stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were computed from the pressure pulsations. After nitroglycerin administration, the HUTT+ Group showed a significant increase in heart rate (92.0 ± 7.3 beats/min vs 68.9 ± 8.7 beats/min, P < 0.0001), with well-maintained systolic BP (111.6 ± 14.1 mm Hg vs 108.8 ± 11.5 mm Hg; P = 0.332) and diastolic BP (66.1 ± 8.5 mm Hg vs 63.1 ± 6.9 mm Hg; P = 0.0913); a significant decrease in SV (53.9 ± 8.0 mL vs 78.6 ± 8.2 mL; P < 0.0001) and CO (4.0 ± 0.5 L/min vs 5.8 ± 1.0 L/min; P < 0.001), and a significant increase in TPR (1.3 ± 0.3 U vs 0.9 ± 0.2 U, P < 0.0011). We tested three hemodynamic parameters (SV, CO, and TPR) as predictors of positive tilt test response with receiver-operating characteristic curve analysis. Our results show that, 2 minutes after nitroglycerin administration, a statistically significant decrease of SV values (<67 mL) strongly predicts (area under the curve, 0.985; P < 0.0001) the HUTT-positive response in healthy patients with recurrent unexplained syncope. © 2015 Wiley Periodicals, Inc.

Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]).

PubMed

Pasupathy, Sivabaskari; Tavella, Rosanna; Grover, Suchi; Raman, Betty; Procter, Nathan E K; Du, Yang Timothy; Mahadavan, Gnanadevan; Stafford, Irene; Heresztyn, Tamila; Holmes, Andrew; Zeitz, Christopher; Arstall, Margaret; Selvanayagam, Joseph; Horowitz, John D; Beltrame, John F

2017-09-05

Contemporary ST-segment-elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging-assessed infarct size. Secondary end points included cardiac magnetic resonance-determined myocardial salvage and creatine kinase kinetics. Of 112 randomized patients with ST-segment-elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance-assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; P =0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37-79) compared with placebo (27%; interquartile range, 14-42; P <0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively ( P =0.08). High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes. Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000. © 2017 American Heart Association, Inc.

Impact of reference-based pricing of nitrates on the use and costs of anti-anginal drugs.

PubMed

Grootendorst, P V; Dolovich, L R; O'Brien, B J; Holbrook, A M; Levy, A R

2001-10-16

Reference-based pricing limits reimbursement for a group of drugs that are deemed therapeutically equivalent to the cost of the lowest-priced product within that group. We estimated the effect of reference-based pricing of nitrate drugs used for long-term prophylaxis on prescribing of and expenditures on nitrates and other anti-anginal drugs dispensed to senior citizens in British Columbia. We assessed trends in the monthly volume of prescriptions of anti-anginal drugs and the associated drug ingredient cost paid by the province's publicly funded drug subsidy program, Pharmacare, and by the patients themselves for the period April 1994 to May 1999. Trends in monthly rates of nitrate expenditures per 100,000 senior citizens before the introduction of reference-based pricing were extrapolated to infer what expenditures would have been without the policy. During the 3 1/2 years after reference-based pricing was introduced, Pharmacare expenditures on nitrates prescribed to senior citizens declined by $14.9 million (95% confidence interval $10.7 to $19.1 million). Most of these savings were due to the lower prices that Pharmacare paid for sustained-release nitroglycerin tablets and the nitroglycerin patch, which were the 2 most frequently prescribed nitrates before the introduction of reference-based pricing; $1.2 million (8%) of the savings represented expenditures by senior citizens who purchased drugs that were only partially reimbursed. There were no compensatory increases in expenditures for other anti-anginal drugs. Use of sublingual nitroglycerin--a marker for deteriorating health in patients with angina--did not increase after the introduction of reference-based pricing. The nitroglycerin patch is now the most frequently prescribed nitrate, owing to the fact that Pharmacare resumed the provision of full subsidies for the drug after its manufacturers voluntarily reduced retail prices. Evidence to date suggests that reference-based pricing of nitrates has achieved its primary goal of reducing drug expenditures. The effects of this policy on patient health, associated health care costs and administrative costs remain to be investigated.

Effects of organic and inorganic nitrate on aortic and carotid haemodynamics in heart failure with preserved ejection fraction.

PubMed

Chirinos, Julio A; Londono-Hoyos, Francisco; Zamani, Payman; Beraun, Melissa; Haines, Philip; Vasim, Izzah; Varakantam, Swapna; Phan, Timothy S; Cappola, Thomas P; Margulies, Kenneth B; Townsend, Raymond R; Segers, Patrick

2017-11-01

To assess the haemodynamic effects of organic vs. inorganic nitrate administration among patients with heart failure with preserved ejection fraction (HFpEF). We assessed carotid and aortic pressure-flow relations non-invasively before and after the administration of 0.4 mg of sublingual nitroglycerin (n = 26), and in a separate sub-study, in response to 12.9 mmoL of inorganic nitrate (n = 16). Nitroglycerin did not consistently reduce wave reflections arriving at the proximal aorta (change in real part of reflection coefficient, 1st harmonic: -0.09; P = 0.01; 2nd harmonic: -0.045, P = 0.16; 3rd harmonic: +0.087; P = 0.05), but produced profound vasodilatation in the carotid territory, with a significant reduction in systolic blood pressure (133.6 vs. 120.5 mmHg; P = 0.011) and a marked reduction in carotid bed vascular resistance (19 580 vs. 13 078 dynes · s/cm 5 ; P = 0.001) and carotid characteristic impedance (3440 vs. 1923 dynes · s/cm 5 ; P = 0.002). Inorganic nitrate, in contrast, consistently reduced wave reflections across the first three harmonics (change in real part of reflection coefficient, 1st harmonic: -0.12; P = 0.03; 2nd harmonic: -0.11, P = 0.01; 3rd harmonic: -0.087; P = 0.09) and did not reduce blood pressure, carotid bed vascular resistance, or carotid characteristic impedance (P = NS). Nitroglycerin produces marked vasodilatation in the carotid circulation, with a pronounced reduction in blood pressure and inconsistent effects on central wave reflections. Inorganic nitrate, in contrast, produces consistent reductions in wave reflections, and unlike nitroglycerin, it does so without significant hypotension or cerebrovascular dilatation. These haemodynamic differences may underlie the different effects on exercise capacity and side effect profile of inorganic vs. organic nitrate in HFpEF. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo.

PubMed

Buscema, Marzia; Matviykiv, Sofiya; Mészáros, Tamás; Gerganova, Gabriela; Weinberger, Andreas; Mettal, Ute; Mueller, Dennis; Neuhaus, Frederik; Stalder, Etienne; Ishikawa, Takashi; Urbanics, Rudolf; Saxer, Till; Pfohl, Thomas; Szebeni, János; Zumbuehl, Andreas; Müller, Bert

2017-10-28

Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear-responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC-Pad formulations in human and porcine sera, along with the nanopharmaceutical-mediated cardiopulmonary responses in pigs. The evaluated formulations comprised of Pad-PC-Pad liposomes, with and without polyethylene glycol on the surface of the liposomes, and nitroglycerin as a model vasodilator. The nitroglycerin incorporation efficiency ranged from 25% to 50%. In human sera, liposome formulations with 20mg/mL phospholipid gave rise to complement activation, mainly via the alternative pathway, as reflected by the rises in SC5b-9 and Bb protein complex concentrations. Formulations having a factor of ten lower phospholipid content did not result in measurable complement activation. The weak complement activation induced by Pad-PC-Pad liposomal formulations was confirmed by the results obtained by performing an in vivo study in a porcine model, where hemodynamic parameters were monitored continuously. Our study suggests that, compared to FDA-approved liposomal drugs, Pad-PC-Pad exhibits less or similar risks of CARPA. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Differential sensitivities of pulmonary and coronary arteries to hemoglobin-based oxygen carriers and nitrovasodilators: study in a bovine ex vivo model of vascular strips.

PubMed

Fonseca, Vera; Avizinis, Jessica; Moon-Massat, Paula; Freilich, Daniel; Kim, Hae Won; Hai, Chi-Ming

2010-01-01

Vasoconstriction is a major adverse effect of first and second generation hemoglobin-based oxygen carriers (HBOCs) that hinders their development as blood substitute. However, intravenous infusion of HBOC-201 (second generation) to patients induces significant pulmonary hypertension without significant coronary vasoconstriction. We compared contractile responses of isolated bovine pulmonary and coronary arterial strips to HBOC-201 and HBOC-205LL.LT.MW600 (third generation), polymerized bovine hemoglobins of different molecular weight, and their attenuation by nitroglycerin, sodium nitroprusside (SNP), and sodium nitrite. Pulmonary arteries developed negligible basal tone, but exhibited HBOC-dependent amplification of phenylephrine-induced contractions. In contrast, coronary arteries developed significant basal tone, and exhibited HBOC-dependent constant force increment to serotonin-induced contractions. Therefore, relative to basal tone, HBOC-induced contractions were greater in pulmonary than coronary arteries. Furthermore, HBOC-205LL.LT.MW600 appeared to be less vasoactive than HBOC-201. Unexpectedly, pulmonary and coronary arteries exhibited differential sensitivities to nitrovasodilators in parallel with their differential sensitivities to HBOC. However, SNP and sodium nitrite induced significant methemoglobin formation from HBOC, whereas nitroglycerin did not. These results suggest that phenotypic differences between pulmonary and coronary vascular smooth muscle cells could explain the differential hypertensive effects of HBOC on pulmonary and coronary circulation in patients. Among the three nitrovasodilators investigated, nitroglycerin appears to be the most promising candidate for attenuating HBOC-induced pulmonary hypertension in older HBOCs.

Adsorption/Desorption Measurements of Nitroglycerin and Dinitrotoluene in Camp Edwards, Massachusetts Soil

DTIC Science & Technology

2010-02-01

87 8 References...without biocide to K7 soil. ................................................ 31 Figure 8 . The 2,4-DNT concentration in the measured aqueous phase (C...28 Table 8 . Adsorption and desorption partitioning

Alternative Pharmacological Management of Vasopressor Extravasation in the Absence of Phentolamine

PubMed Central

Plum, Michelle; Moukhachen, Oussayma

2017-01-01

Vasopressor extravasation is a rare adverse drug reaction that can lead to tissue damage, ischemia, and necrosis of the affected area when vasopressors are administered peripherally. Phentolamine, a nonselective, reversible alpha antagonist, is the current standard treatment for this adverse reaction, but it is often unavailable for use. This review seeks to synthesize the available data in order to recommend alternative pharmacological options for use when phentolamine is not available. After an extensive literature search, 16 publications were reviewed. A treatment algorithm was created that recommends a combination of subcutaneous terbutaline, a selective beta2 agonist, and topical nitroglycerin, an organic nitrate, for adults; and topical nitroglycerin monotherapy for children younger than 2 years of age. However, further research and case reports are required in order to establish a new standard of care for the treatment of vasopressor extravasation. PMID:28890646

Historical perspective and contemporary management of acute coronary syndromes: from MONA to THROMBINS2.

PubMed

Kline, Kristopher P; Conti, C Richard; Winchester, David E

2015-01-01

Acute coronary syndrome (ACS) remains a major burden on morbidity and mortality in the United States. Medical professionals and students often use the mnemonic 'MONA' (morphine, oxygen, nitroglycerin and aspirin) to recall treatments for ACS; however, this list of therapies is outdated. We provide a historical perspective on 'MONA,' attempt to uncover its origin in the medical literature, and demonstrate the myriad changes that have occurred over the last 50 years of ACS management. We have developed a novel mnemonic, 'THROMBINS2' (thienopyridines, heparin/enoxaparin, renin-angiotensin system blockers, oxygen, morphine, beta blocker, intervention, nitroglycerin, statin/salicylate) to help bedside clinicians recall all the elements of contemporary ACS management. We demonstrate the mortality benefit for each component of contemporary ACS management, correlating the continued improvement with historical data on mortality after myocardial infarction. We encourage providers to utilize this mnemonic to explore options and guide treatments in ACS patients.

A systematic tandem mass spectrometric study of anion attachment for improved detection and acidity evaluation of nitrogen-rich energetic compounds.

PubMed

Gaiffe, Gabriel; Bridoux, Maxime C; Costanza, Christine; Cole, Richard B

2018-01-01

The development of rapid, efficient, and reliable detection methods for the characterization of energetic compounds is of high importance to security forces concerned with terrorist threats. With a mass spectrometric approach, characteristic ions can be produced by attaching anions to analyte molecules in the negative ion mode of electrospray ionization mass spectrometry (ESI-MS). Under optimized conditions, formed anionic adducts can be detected with higher sensitivities as compared with the deprotonated molecules. Fundamental aspects pertaining to the formation of anionic adducts of 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX), 1,3,5-trinitro-1,3,5-triazinane (RDX), pentaerythritol tetranitrate (PETN), nitroglycerin (NG), and 1,3,5-trinitroso-1,3,5-triazinane energetic (R-salt) compounds using various anions have been systematically studied by ESI-MS and ESI tandem mass spectrometry (collision-induced dissociation) experiments. Bracketing method results show that the gas-phase acidities of PETN, RDX, and HMX fall between those of HF and acetic acid. Moreover, PETN and RDX are each less acidic than HMX in the gas phase. Nitroglycerin was found to be the most acidic among the nitrogen-rich explosives studied. The ensemble of bracketing results allows the construction of the following ranking of gas-phase acidities: PETN (1530-1458 kJ/mol) > RDX (approximately 1458 kJ/mol) > HMX (approximately 1433 kJ/mol) > nitroglycerin (1427-1327.8 kJ/mol). Copyright © 2017 John Wiley & Sons, Ltd.

Synthesis of a new energetic nitrate ester

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chavez, David E

2008-01-01

Nitrate esters have been known as useful energetic materials since the discovery of nitroglycerin by Ascanio Sobrero in 1846. The development of methods to increase the safety and utility of nitroglycerin by Alfred Nobel led to the revolutionary improvement in the utility of nitroglycerin in explosive applications in the form of dynamite. Since then, many nitrate esters have been prepared and incorporated into military applications such as double-based propellants, detonators and as energetic plasticizers. Nitrate esters have also been shown to have vasodilatory effects in humans and thus have been studied and used for treatments of ailments such as angina.more » The mechanism of the biological response towards nitrate esters has been elucidated recently. Interestingly, many of the nitrate esters used for military purposes are liquids (ethylene glycol dinitrate, propylene glycol dinitrate, etc). Pentaerythritol tetranitrate (PETN) is one of the only solid nitrate esters, besides nitrocellulose, that is used in any application. Unfortunately, PETN melting point is above 100 {sup o}C, and thus must be pressed as a solid for detonator applications. A more practical material would be a melt-castable explosive, for potential simplification of manufacturing processes. Herein we describe the synthesis of a new energetic nitrate ester (1) that is a solid at ambient temperatures, has a melting point of 85-86 {sup o}C and has the highest density of any known nitrate ester composed only of carbon, hydrogen, nitrogen and oxygen. We also describe the chemical, thermal and sensitivity properties of 1 as well as some preliminary explosive performance data.« less

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

PubMed

Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

2013-09-08

Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple comparisons with the best' approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.

49 CFR 173.54 - Forbidden explosives.

Code of Federal Regulations, 2013 CFR

2013-10-01

... subpart. (b) An explosive mixture or device containing a chlorate and also containing: (1) An ammonium... explosive. (d) Propellants that are unstable, condemned or deteriorated. (e) Nitroglycerin, diethylene... detonator. (h) Fireworks containing yellow or white phosphorus. (i) A toy torpedo, the maximum outside...

49 CFR 173.54 - Forbidden explosives.

Code of Federal Regulations, 2014 CFR

2014-10-01

... subpart. (b) An explosive mixture or device containing a chlorate and also containing: (1) An ammonium... explosive. (d) Propellants that are unstable, condemned or deteriorated. (e) Nitroglycerin, diethylene... detonator. (h) Fireworks containing yellow or white phosphorus. (i) A toy torpedo, the maximum outside...

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics.

PubMed

Divakaran, Sanjay; Loscalzo, Joseph

2017-11-07

The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and nonhemodynamic effects of organic nitrate therapy, via both nitric oxide-dependent and -independent mechanisms. Nitrates are rapidly absorbed from mucous membranes, the gastrointestinal tract, and the skin; thus, nitroglycerin is available in a number of preparations for delivery via several routes: oral tablets, sublingual tablets, buccal tablets, sublingual spray, transdermal ointment, and transdermal patch, as well as intravenous formulations. Organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina. They are also used in the treatment of subsets of patients with heart failure and pulmonary hypertension. One major limitation of the use of nitrates is the development of tolerance. Although several agents have been studied for use in the prevention of nitrate tolerance, none are currently recommended owing to a paucity of supportive clinical data. Only 1 method of preventing nitrate tolerance remains widely accepted: the use of a dosing strategy that provides an interval of no or low nitrate exposure during each 24-h period. Nitric oxide's important role in several cardiovascular disease mechanisms continues to drive research toward finding novel ways to affect both endogenous and exogenous sources of this key molecular mediator. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The efficacy of Labetalol versus Nitroglycerin for induction of controlled hypotension during sinus endoscopic surgery. A prospective, double-blind and randomized study.

PubMed

El-Shmaa, Nagat S; Ezz, Hoda Alsaid Ahmed; Younes, Ahmed

2017-06-01

To assess the efficacy of labetalol versus nitroglycerin for induction of controlled hypotension during sinus endoscopic surgery. A prospective, double-blind and randomized study. Carried out in operating room in university hospital. 60 patients of both sexes, American Society of Anesthesiologists (ASA) physical status I and II, age range from 20 to 60years; scheduled for elective sinus endoscopic surgery under general anesthesia (GA). Patients were divided into two groups (30 each). NTG group received nitroglycerin infusion at a dose of 2-5μg/kg/min, LAB group received labetalol infusion at a dose of 0.5-2mg/min. Surgical condition was assessed by surgeon using average category scale (ACS) of 0-5, a value of 2-3 being ideal. In both groups mean arterial blood pressure (MAP) was gradually reduced till the ideal ACS for assessment of surgical condition, the target of ACS was 2-3 or lower. Both studied drugs achieved desired hypotension and improved visualization of surgical field by decreasing bleeding in the surgical site, but ideal surgical conditions were created at mild hypotension (MAP 70-75) in LAB group while same conditions were created at MAP of 65-69mmHg in NTG group. Mean heart rate (HR) was significantly higher in NTG group as compared to LAB group. Blood loss decreased significantly in LAB group. Both labetalol and NTG are effective and safe drugs for induction of controlled hypotension during sinus endoscopic surgery. While, labetalol was better as it offered optimum operative condition with mild decrease in blood pressure, decreased surgical bleeding and less tachycardia during the surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function.

PubMed

O'Neill, Marie S; Veves, Aristidis; Zanobetti, Antonella; Sarnat, Jeremy A; Gold, Diane R; Economides, Panayiotis A; Horton, Edward S; Schwartz, Joel

2005-06-07

Epidemiological studies suggest that people with diabetes are vulnerable to cardiovascular health effects associated with exposure to particle air pollution. Endothelial and vascular function is impaired in diabetes and may be related to increased cardiovascular risk. We examined whether endothelium-dependent and -independent vascular reactivity was associated with particle exposure in individuals with and without diabetes. Study subjects were 270 greater-Boston residents. We measured 24-hour average ambient levels of air pollution (fine particles [PM2.5], particle number, black carbon, and sulfates [SO4(2-)]) approximately 500 m from the patient examination site. Pollutant concentrations were evaluated for associations with vascular reactivity. Linear regressions were fit to the percent change in brachial artery diameter (flow mediated and nitroglycerin mediated), with the particulate pollutant index, apparent temperature, season, age, race, sex, smoking history, and body mass index as predictors. Models were fit to all subjects and then stratified by diagnosed diabetes versus at risk for diabetes. Six-day moving averages of all 4 particle metrics were associated with decreased vascular reactivity among patients with diabetes but not those at risk. Interquartile range increases in SO4(2-) were associated with decreased flow-mediated (-10.7%; 95% CI, -17.3 to -3.5) and nitroglycerin-mediated (-5.4%; 95% CI, -10.5 to -0.1) vascular reactivity among those with diabetes. Black carbon increases were associated with decreased flow-mediated vascular reactivity (-12.6%; 95% CI, -21.7 to -2.4), and PM2.5 was associated with nitroglycerin-mediated reactivity (-7.6%; 95% CI, -12.8 to -2.1). Effects were stronger in type II than type I diabetes. Diabetes confers vulnerability to particles associated with coal-burning power plants and traffic.

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Discussion Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. Trial registration ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742. PMID:24010992

Mechanism of vasodilation induced by alpha-human atrial natriuretic polypeptide in rabbit and guinea-pig renal arteries.

PubMed Central

Fujii, K; Ishimatsu, T; Kuriyama, H

1986-01-01

Effects of alpha-human atrial natriuretic polypeptide (alpha-HANP) on electrical and mechanical properties of smooth muscle cells of the guinea-pig and rabbit renal arteries and of the guinea-pig mesenteric artery were investigated. alpha-HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea-pig and rabbit renal arteries. In the guinea-pig mesenteric and renal arteries, alpha-HANP (up to 10 nM) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) of excitatory junction potentials nor on action potentials. In the guinea-pig renal artery, alpha-HANP (up to 10 nM) had no effect on the depolarization induced by noradrenaline (NA) (up to 10 microM) but markedly inhibited NA-induced contraction. alpha-HANP (10 nM) slightly inhibited the K-induced contraction. In the rabbit renal artery, alpha-HANP (10 nM) inhibited the NA-induced contraction and to a lesser extent the K-induced contraction. In the rabbit renal artery, the effects of alpha-HANP on the release of Ca from the cellular storage by two applications of NA, and its re-storage, were investigated in Ca-free solution containing 2 mM-EGTA. When 5 nM-alpha-HANP was applied before and during the first application of 0.5 microM-NA, the contraction was markedly inhibited but the contraction to a second application of 10 microM-NA was potentiated. If the first dose of NA was 10 microM the effect was very small. Under the same experimental procedures, nitroglycerine (10 microM) showed almost the same effects as alpha-HANP on the NA-induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca-free solution, alpha-HANP (5 nM) and nitroglycerine (10 microM) inhibited both contractions to the same extent. In the rabbit renal artery, applications of alpha-HANP or nitroglycerine increased the amount of guanosine 3',5'-phosphate (cyclic GMP) in a dose-dependent manner. However, a much higher concentration of nitroglycerine was required (2 X 10(3) times). In the rabbit renal artery, hydrolysis of phosphatidyl inositol 4,5-bisphosphate (PI-P2) activated by 0.5 microM-NA was inhibited by alpha-HANP, in a dose-dependent manner, but activation by 10 microM-NA was not inhibited by alpha-HANP (up to 100 nM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3025429

List of Error-Prone Abbreviations, Symbols, and Dose Designations

MedlinePlus

... unit dose (e.g., diltiazem 125 mg IV infusion “UD” misin- terpreted as meaning to give the entire infusion as a unit [bolus] dose) Use “as directed” ... Names Intended Meaning Misinterpretation Correction “Nitro” drip nitroglycerin infusion Mistaken as sodium nitroprusside infusion Use complete drug ...

77 FR 7586 - Draft Guidance for Industry on Bioequivalence Recommendation for Nitroglycerin Metered Spray...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... though we have not requested comparative in vitro studies, in vitro studies outlined in the 2002 guidance.... The recommendations provide specific guidance on the design of bioequivalence (BE) studies to support... draft guidance for industry on the Agency's recommendations for BE studies to support ANDAs for...

Intraoperative "Kounis syndrome" that improved electrocardiography changes and hemodynamic situation after administering nitroglycerine.

PubMed

Sánchez, Victoria O; Roca, Luisa C; Moreno, Angel Del P

2014-01-01

A 58-year-old female without cardiovascular risk factors, was going to be operated to repair the rotator cuff. Induction and interscalene brachial plexus block were uneventful, but after her placement for surgery the patient started with severe bronchospasm, hypotension, cutaneous allergic reaction and ST elevation on the electrocardiogram. An anaphylactic shock was suspected and treated but until the perfusion of nitroglycerina was started no electrocardiographic changes resolved. After necessary diagnostic test the final diagnosis was variant I of Kounis syndrome due to cefazolin and rocuronium. Ephinephrine is the cornerstone of treatment for anaphylaxis but should we use it if the anaphylactic reaction is also accompanied by myocardial ischemia? The answer is that we should not use it because myocardial ischemia in this syndrome is caused by vasospasm, so it would be more useful drugs such as nitroglycerin. But what if we do not know if it is a Kounis syndrome or not? In this article we report our experience that maybe could help you in a similar situation. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Optimization of focused ultrasonic extraction of propellant components determined by gas chromatography/mass spectrometry.

PubMed

Fryš, Ondřej; Česla, Petr; Bajerová, Petra; Adam, Martin; Ventura, Karel

2012-09-15

A method for focused ultrasonic extraction of nitroglycerin, triphenyl amine and acetyl tributyl citrate presented in double-base propellant samples following by the gas chromatography/mass spectrometry analysis was developed. A face-centered central composite design of the experiments and response surface modeling was used for optimization of the time, amplitude and sample amount. The dichloromethane was used as the extractant solvent. The optimal extraction conditions with respect to the maximum yield of the lowest abundant compound triphenyl amine were found at the 20 min extraction time, 35% amplitude of ultrasonic waves and 2.5 g of the propellant sample. The results obtained under optimal conditions were compared with the results achieved with validated Soxhlet extraction method, which is typically used for isolation and pre-concentration of compounds from the samples of explosives. The extraction yields for acetyl tributyl citrate using both extraction methods were comparable; however, the yield of ultrasonic extraction of nitroglycerin and triphenyl amine was lower than using Soxhlet extraction. The possible sources of different extraction yields are estimated and discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Enzymatic remediated biodegradation of propylene glycol 1,2-dinitrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meng, M.; Geelhaar, L.; Speedie, M.K.

1995-12-31

Two bacterial species, Enterobacter agglomerans and Bacillus thuringiensis/cereus, which were selected from nitroglycerin (GTN) contaminated soil, have previously been shown to have denitrating ability on nitroglycerin. This abstract presents the investigation of the cell free extracts from both microorganisms for the degradation of another nitrate ester contaminant; propylene glycol 1,2-dinitrate (PGDN). This compound has been previously considered resistant to the biodegradation. In order to probe the pathway, the whole process was monitored by using [1-{sup 14}C]-PGDN as substrate and the intermediates were identified by HPLC and TLC chromatography. Long term biodegradation experiments have shown that the enzymes in the cytoplasmmore » fraction of Bacillus thuringiensis/cereus and the membrane fraction of Enterobacter agglomerans convert PGDN successively into propylene glycol 1-mononitrate (1-PGMN) and propylene glycol 2-mononitrate (2-PGMN), and finally, propylene glycol. The capacity to achieve sequential and complete degradation of PGDN implies that it follows a similar mechanism to that observed in the GTN degradation. Cofactor requirements for PGDN breakdown have been studied, it was found that no dissociable, dialyzable cofactors are required.« less

Effects of nitrates on mortality in acute myocardial infarction and in heart failure

PubMed Central

Held, P.

1992-01-01

1 Seven randomized controlled trials of intravenous nitroglycerin in a total of about 850 patients have been reported. Overall, there were 51 deaths (12.5%) in the nitroglycerin group and 87 (20%) in the control group. This indicates a 48% reduction in the odds of death (P < 0.001, 95% confidence limits (25% to 64%)). 2 There are five randomized trials of oral nitrates after acute myocardial infarction. In these trials, 11.8% of the patients in the nitrate group compared with 13.3% in the control group died. This indicates a nonsignificant 12% reduction in the odds of death but the 95% confidence interval overlaps widely with the i.v. trials. If all trials of i.v. or oral nitrates are considered the reduction in the odds of death is 32% (P < 0.01). 3 Nitrates have a beneficial effect on haemodynamics in heart failure but the data on mortality effects are sparse. In combination with hydralazine, however, long-term mortality was reduced in the V-HEFT trial of chronic heart failure. PMID:1633075

Prehospital Nitroglycerin Safety in Inferior ST Elevation Myocardial Infarction.

PubMed

Robichaud, Laurie; Ross, Dave; Proulx, Marie-Hélène; Légaré, Sébastien; Vacon, Charlene; Xue, Xiaoqing; Segal, Eli

2016-01-01

Patients with inferior ST elevation myocardial infarction (STEMI), associated with right ventricular infarction, are thought to be at higher risk of developing hypotension when administered nitroglycerin (NTG). However, current basic life support (BLS) protocols do not differentiate location of STEMI prior to NTG administration. We sought to determine if NTG administration is more likely to be associated with hypotension (systolic blood pressure < 90 mmHg) in inferior STEMI compared to non-inferior STEMI. We conducted a retrospective chart review of prehospital patients with chest pain of suspected cardiac origin and computer-interpreted prehospital ECGs indicating "ACUTE MI." We included all local STEMI cases identified as part of our STEMI registry. Univariate analysis was used to compare differences in proportions of hypotension and drop in systolic blood pressure ≥ 30 mmHg after nitroglycerin administration between patients with inferior wall STEMI and those with STEMI in another region (non-inferior). Multiple variable logistic regression analysis was also used to assess the study outcomes while controlling for various factors. Over a 29-month period, we identified 1,466 STEMI cases. Of those, 821 (56.0%) received NTG. We excluded 16 cases because of missing data. Hypotension occurred post NTG in 38/466 inferior STEMIs and 30/339 non-inferior STEMIs, 8.2% vs. 8.9%, p = 0.73. A drop in systolic blood pressure ≥ 30 mmHg post NTG occurred in 23.4% of inferior STEMIs and 23.9% of non-inferior STEMIs, p = 0.87. Interrater agreement for chart review of the primary outcome was excellent (κ = 0.94). NTG administration to patients with chest pain and inferior STEMI on their computer-interpreted electrocardiogram is not associated with a higher rate of hypotension compared to patients with STEMI in other territories. Computer interpretation of inferior STEMI cannot be used as the sole predictor for patients who may be at higher risk for hypotension following NTG administration.

Activation of the nuclear factor E2-related factor 2/anitioxidant response element alleviates the nitroglycerin-induced hyperalgesia in rats.

PubMed

Di, Wei; Shi, Xiaolei; Lv, Hua; Liu, Jun; Zhang, Hong; Li, Zhiwei; Fang, Yannan

2016-12-01

Antioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats. The expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot. Immunofluorescence was used to demonstrate the cell-specific localization of Nrf2 in TNC. Sulforaphane, a Nrf2 activator, was administered to NTG-induced rats. Then, the number of c-Fos- and nNOS-immunoreactive neurons in TNC was evaluated using immunofluorescence, and c-Fos and nNOS protein levels were quantified using western blot. Von Frey hair testing was used to evaluate the tactile thresholds of rats at different time points in different groups. Total cellular and nuclear levels of the proteins Nrf2, HO1, and NQO1 were elevated in TNC after NTG injection, and Nrf2 was found to be located in the nucleus and cytoplasm of the neurons. Sulforaphane pretreatment significantly increased the nuclear Nrf2, HO1, and NQO1 levels in TNC. In addition, sulforaphane exposure effectively inhibited the expression of nNOS and c-Fos, reduced the number of nNOS and c-Fos immunoreactive neurons in TNC, and attenuated the tactile thresholds induced by NTG injection. Oxidative stress was involved in nitroglycerin-induced hyperalgesia. Activation of the Nrf2/ARE pathway inhibited the activation of TGVS and prevented the induction of hyperalgesia. Sulforaphane might therefore be an effective agent for hyperalgesia. Further studies are needed to discover the underlying mechanisms of the process.

Cardiovascular effects of sildenafil citrate and recommendations for its use.

PubMed

Kloner, R A; Zusman, R M

1999-09-09

Sildenafil citrate is the first orally active therapy proved to be effective and safe treatment for erectile dysfunction (ED). Because men with cardiovascular disease are at increased risk of developing ED, and because ED and cardiovascular disease share important risk factors, attention has focused recently on the use of sildenafil in these men. When used in combination with nitroglycerin and other nitric oxide (NO) donors, sildenafil may potentiate major drops in blood pressure. Use of nitrate antianginal agents are an absolute contraindication to sildenafil use. In normotensive men and in men receiving antihypertensive medications evaluated in Phase II/III clinical trials, sildenafil use at the recommended doses (25-100 mg 1 hour before sexual intercourse and no more than once daily) was associated with modest, transient reductions in blood pressure and negligible effects on heart rate. In a more recent study, sildenafil was well tolerated in patients receiving antihypertensive medications and was not associated with major decreases in blood pressure. From the time of its approval in the United States in March 1998 through mid-November 1998, with approximately 6 million prescriptions written, 130 deaths were reported by the US Food and Drug Administration (FDA). Seventy-seven of the men who died had documented cardiovascular events. Sixteen men took or were administered nitroglycerin or an organic nitrate; 3 others had nitroglycerin in their possession. Physician prescribing guidelines issued by the American College of Cardiology/American Heart Association (ACC/AHA) recommend caution when prescribing sildenafil to men with certain cardiovascular conditions, liver or kidney disease, and to those taking medications that may prolong sildenafil's half-life (e.g., erythromycin or cimetidine). Those with known or suspected coronary artery disease may benefit from an exercise test to determine whether resumption of sexual activity with use of sildenafil is likely to be associated with an increased risk of myocardial ischemia.

Treating angina pectoris by acupuncture therapy.

PubMed

Xu, Lixian; Xu, Hao; Gao, Wei; Wang, Wei; Zhang, Hui; Lu, Dominic P

2013-01-01

Acupuncture therapy on PC 6 (Neiguan) has a therapeutic effect on cardiac and chest ailments including angina pectoris. Additional beneficial acupuncture points are PC 4 (Ximen), HT 7 (Shenmen point), PC 7 (Daling point), PC 5 (Jianshi point), PC 3 (Quze point), CV 17 (Danzhong point), CV 6 (Qihai point), BL 15 (Xinshu point), L 20 (Pishu point), BL 17 (Geshu point), BL23 (Shenshu point), BL18 (Ganshu point), HT 5 (Tongli point), and ST36 (Zusanli point). Acupuncture not only quickly relieve the symptoms of acute angina pectoris, but also improve nitroglycerine's therapeutic effects. Therefore, it is an efficient simple therapeutic method used for emergency and for regular angina treatment. Review of studies on acupuncture therapy has shown effectiveness were between 80% to 96.2% that are almost as effective as conventional drug regimen. When compared with conventional medical treatment, the acupuncture therapy shows the obvious advantage of lacking, adverse side effects commonly associated with the Western anti-anginal drugs such as 1) Nitroglycerine (headache--63% with nitroglycerine patch and 50% with spray; syncope--4%; and dizziness--8% with patch; hypotension--4% with patch; and increased angina 2% with patch). 2) Isosorbide mononitrate (dizziness--3 to 5%; nausea/vomiting--2 to 4% and other reactions including hypotension, and syncope even with small doses). 3) Propranolol (bradycardia, chest pain, hypotension, worsening of AV conduction disturbance, Raynaud's syndrome, mental depression, hyperglycemia, etc.). Many conventional anti-anginal medications cause inter-drug reactions with other medications the patients taking for other diseases. Whereas, acupuncture therapy does not pose such an interference with patient's medications. Nevertheless, surgery is still the treatment of choice when acupuncture or conventional drug therapy fails. Combination of conventional drug therapy and acupuncture would considerably decrease the frequency and the required dosage of drug taking, thereby decreasing the unpleasant side effects of the drug therapy.

Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.

PubMed

Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H; English, Mark; Talcott, Susanne; Jaffe, Iris Z; Christou, Demetra D

2016-01-01

Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 years; mean±SE, 53-79 years) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4 mg) following eplerenone (100 mg/dose, 2 doses, 24h between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6%, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOS(Ser1177) to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5%, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77±4/2 mmHg, P≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure. Copyright © 2015 Elsevier Inc. All rights reserved.

Field Demonstration Report Applied Innovative Technologies for Characterization of Nitrocellulose- and Nitroglycerine Contaminated Buildings and Soils, Rev 1

DTIC Science & Technology

2007-01-05

positive / false negatives. The quantitative on-site methods were evaluated using linear regression analysis and relative percent difference (RPD) comparison...Conclusion ...............................................................................................3-9 3.2 Quantitative Analysis Using CRREL...3-37 3.3 Quantitative Analysis for NG by GC/TID.........................................................3-38 3.3.1 Introduction

14 CFR Appendix A to Part 121 - First Aid Kits and Emergency Medical Kits

Code of Federal Regulations, 2013 CFR

2013-01-01

..., 50cc 1 Epinephrine 1:1000, single dose ampule or equivalent) 2 Diphenhydramine HC1 injection, single dose ampule or equivalent 2 Nitroglycerin tablets 10 Basic instructions for use of the drugs in the kit 1 protective nonpermeable gloves or equivalent 1 pair 2. As of April 12, 2004, at least one approved...

14 CFR Appendix A to Part 121 - First Aid Kits and Emergency Medical Kits

Code of Federal Regulations, 2010 CFR

2010-01-01

..., 50cc 1 Epinephrine 1:1000, single dose ampule or equivalent) 2 Diphenhydramine HC1 injection, single dose ampule or equivalent 2 Nitroglycerin tablets 10 Basic instructions for use of the drugs in the kit 1 protective nonpermeable gloves or equivalent 1 pair 2. As of April 12, 2004, at least one approved...

14 CFR Appendix A to Part 121 - First Aid Kits and Emergency Medical Kits

Code of Federal Regulations, 2014 CFR

2014-01-01

..., 50cc 1 Epinephrine 1:1000, single dose ampule or equivalent) 2 Diphenhydramine HC1 injection, single dose ampule or equivalent 2 Nitroglycerin tablets 10 Basic instructions for use of the drugs in the kit 1 protective nonpermeable gloves or equivalent 1 pair 2. As of April 12, 2004, at least one approved...

14 CFR Appendix A to Part 121 - First Aid Kits and Emergency Medical Kits

Code of Federal Regulations, 2011 CFR

2011-01-01

..., 50cc 1 Epinephrine 1:1000, single dose ampule or equivalent) 2 Diphenhydramine HC1 injection, single dose ampule or equivalent 2 Nitroglycerin tablets 10 Basic instructions for use of the drugs in the kit 1 protective nonpermeable gloves or equivalent 1 pair 2. As of April 12, 2004, at least one approved...

14 CFR Appendix A to Part 121 - First Aid Kits and Emergency Medical Kits

Code of Federal Regulations, 2012 CFR

2012-01-01

..., 50cc 1 Epinephrine 1:1000, single dose ampule or equivalent) 2 Diphenhydramine HC1 injection, single dose ampule or equivalent 2 Nitroglycerin tablets 10 Basic instructions for use of the drugs in the kit 1 protective nonpermeable gloves or equivalent 1 pair 2. As of April 12, 2004, at least one approved...

Uptake and Transformation of the Propellants 2,4-DNT, Perchlorate and Nitroglycerin by Grasses

DTIC Science & Technology

2006-07-31

were detected in the leachate , an average removal of 66%. These results indicate no apparent benefit to phytoremediation of soil contaminated with GTN...degradation was nearly 100% in Indian grass. Degradation in perchlorate and GTN was by bacteria. 15. SUBJECT TERMS phytoremediation , explosives, propellants...9 1. 1. Phytoremediation ........................................................................... 10 1.2. 2,4-DNT

Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects.

PubMed

Ardekani, Soroush; Scott, Harry A; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R; Wilson, Sean M; Mohideen, Umar; Ghosh, Kaustabh

2015-11-20

Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies.

Transdermal nitroglycerin as an adjuvant to patient-controlled morphine analgesia after total knee arthroplasty

PubMed Central

Orbach-Zinger, Sharon; Lenchinsky, Artium; Paul-Kesslin, Lesley; Velks, Steven; Salai, Moses; Eidelman, Leonid A

2009-01-01

BACKGROUND: Nitroglycerin (NTG) has been shown to be a useful adjunct for pain treatment without increasing adverse side effects. The effects of NTG on postoperative morphine consumption after knee replacement were evaluated. METHODS: After undergoing total knee replacement, patients receiving patient-controlled morphine analgesia were randomly assigned to receive either an NTG or a placebo patch. The blinded investigator assessed each patient using a visual analogue scale at rest and while moving, as well as the patient’s morphine requirements, sedation score, sleep quality, nausea and vomiting, vital signs and postoperative bleeding. RESULTS: Two of the patients in the NTG group suffered postoperative myocardial infarctions after removal of the patch. Because of these two serious adverse effects, the study was stopped prematurely. In the subset of patients studied, NTG conferred no advantage over placebo in pain control (visual analogue scale at rest or during movement) and in satisfaction scores. CONCLUSIONS: The use of NTG patches conferred no advantage over the use of placebo in patients receiving patient-controlled morphine analgesia after total knee replacement. Two myocardial infarcts occurred in this group. Therefore, the safety of postoperative NTG patch use for pain control must be questioned. PMID:19532851

Catalysis of nitrite generation from nitroglycerin by glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

PubMed

Seabra, Amedea B; Ouellet, Marc; Antonic, Marija; Chrétien, Michelle N; English, Ann M

2013-11-30

Vascular relaxation to nitroglycerin (glyceryl trinitrate; GTN) requires its bioactivation by mechanisms that remain controversial. We report here that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the release of nitrite from GTN. In assays containing dithiothreitol (DTT) and NAD(+), the GTN reductase activity of purified GAPDH produces nitrite and 1,2-GDN as the major products. A vmax of 2.6nmolmin(-)(1)mg(-)(1) was measured for nitrite production by GAPDH from rabbit muscle and a GTN KM of 1.2mM. Reductive denitration of GTN in the absence of DTT results in dose- and time-dependent inhibition of GAPDH dehydrogenase activity. Disulfiram, a thiol-modifying drug, inhibits both the dehydrogenase and GTN reductase activity of GAPDH, while DTT or tris(2-carboxyethyl)phosphine reverse the GTN-induced inhibition. Incubation of intact human erythrocytes or hemolysates with 2mM GTN for 60min results in 50% inhibition of GAPDH's dehydrogenase activity, indicating that GTN is taken up by these cells and that the dehydrogenase is a target of GTN. Thus, erythrocyte GAPDH may contribute to GTN bioactivation. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice

PubMed Central

Bates, EA; Nikai, T; Brennan, KC; Fu, Y-H; Charles, AC; Basbaum, AI; Ptáček, LJ; Ahn, AH

2016-01-01

The association between the clinical use of nitroglycerin (NTG) and headache has led to the examination of NTG as a model trigger for migraine and related headache disorders, both in humans and laboratory animals. In this study in mice, we hypothesized that NTG could trigger behavioural and physiological responses that resemble a common manifestation of migraine in humans. We report that animals exhibit a dose-dependent and prolonged NTG-induced thermal and mechanical allodynia, starting 30–60 min after intraperitoneal injection of NTG at 5–10 mg/kg. NTG administration also induced Fos expression, an anatomical marker of neuronal activity in neurons of the trigeminal nucleus caudalis and cervical spinal cord dorsal horn, suggesting that enhanced nociceptive processing within the spinal cord contributes to the increased nociceptive behaviour. Moreover, sumatriptan, a drug with relative specificity for migraine, alleviated the NTG-induced allodynia. We also tested whether NTG reduces the threshold for cortical spreading depression (CSD), an event considered to be the physiological substrate of the migraine aura. We found that the threshold of CSD was unaffected by NTG, suggesting that NTG stimulates migraine mechanisms that are independent of the regulation of cortical excitability. PMID:19489890

Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats.

PubMed

Sufka, Kenneth J; Staszko, Stephanie M; Johnson, Ainslee P; Davis, Morgan E; Davis, Rachel E; Smitherman, Todd A

2016-01-01

This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan. Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, pain facial ratings, and cool (5 °C) and warm (46 °C) tail dip. The first two experiments demonstrated that repeated (n = 5) but not single NTG injections produced photophobia, decreased activity, and yielded less weight gain than saline injections. Experiment 3 showed that sumatriptan attenuated hypoactivity, reduced facial expressions of pain, and reversed weight alterations in a dose-dependent manner. These findings identify numerous clinical homologies of a recurrent NTG rat migraine model that may be useful for screening novel pharmacotherapies.

Effects of nitroglycerin and nitroprusside on vascular capacitance of anesthetized ganglion-blocked dogs.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1991-10-01

To determine whether changes in vascular capacitance induced by nitroglycerin (NTG) and nitroprusside were due to changes in compliance or unstressed vascular volume, doses producing similar reductions in arterial pressure (Psa) were studied on separate days in six dogs anesthetized and ventilated with pentobarbital after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline blood volumes and after increases of 5 and 10 ml/kg. Central blood volumes (CBVs, pulmonary artery to aortic root) were determined from transit times, and separately measured cardiac output (CO) was estimated by thermodilution (right atrium to pulmonary artery). NTG and nitroprusside produced similar reductions in Psa and Pmcf without significantly altering right atrial pressure (Pra), pressure gradient for venous return, or CO. Total vascular compliance was not altered, but total vascular capacitance was increased on an average of 4.0 +/- 1.4 ml/kg after NTG and 3.0 +/- 1.3 ml/kg after nitroprusside by increases in unstressed volume. Both drugs caused a variable reduction in CBV, averaging 2 ml/kg. Thus, both drugs produced a large increase in peripheral venous capacitance by increasing unstressed vascular volume without altering total vascular compliance.

Stable isotopes of nitrate reflect natural attenuation of propellant residues on military training ranges.

PubMed

Bordeleau, Geneviève; Savard, Martine M; Martel, Richard; Smirnoff, Anna; Ampleman, Guy; Thiboutot, Sonia

2013-08-06

Nitroglycerin (NG) and nitrocellulose (NC) are constituents of double-base propellants used notably for firing antitank ammunitions. Nitroglycerin was detected in soil and water samples from the unsaturated zone (pore water) at an active antitank firing position, where the presence of high nitrate (NO3(-)) concentrations suggests that natural attenuation of NG is occurring. However, concentrations alone cannot assess if NG is the source of NO3(-), nor can they determine which degradation processes are involved. To address this issue, isotopic ratios (δ(15)N, δ(18)O) were measured for NO3(-) produced from NG and NC through various controlled degradation processes and compared with ratios measured in field pore water samples. Results indicate that propellant combustion and degradation mediated by soil organic carbon produced the observed NO3(-) in pore water at this site. Moreover, isotopic results are presented for NO3(-) produced through photolysis of propellant constituents, which could be a dominant process at other sites. The isotopic data presented here constitute novel information regarding a source of NO3(-) that was practically not documented before and a basis to study the contamination by energetic materials in different contexts.

Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction.

PubMed

Pieper, G M; Siebeneich, W

1998-07-01

Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. In this study, we examined the efficacy of long-term treatment with the antioxidant, N-acetylcysteine, in preventing the development of defective endothelium-dependent relaxation in streptozotocin-induced, Sprague-Dawley diabetic rats. At 48 h after injection of streptozotocin, a portion of diabetic rats received 250 mg/L N-acetylcysteine in drinking water for a total duration of 8 weeks. Oral administration did not alter the increase in blood glucose or the reduction in serum insulin but did modestly reduce total glycosylated hemoglobin. In precontracted thoracic aortic rings suspended in isolated tissue baths, endothelium-dependent relaxation to acetylcholine was impaired in diabetic rings compared with control rings. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term oral administration of N-acetylcysteine did not alter responses to nitroglycerin but completely prevented the defective relaxation to acetylcholine. These studies indicate a dissociation between glycemic control and correction of endothelial dysfunction and suggest that long-term exposure to reactive oxygen subsequent to diabetes rather than hyperglycemia per se is responsible for the development of endothelial dysfunction in diabetes mellitus.

Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

NASA Astrophysics Data System (ADS)

Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

2015-11-01

Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies.

Poor oral health, that is, decreased frequency of tooth brushing, is associated with endothelial dysfunction.

PubMed

Kajikawa, Masato; Nakashima, Ayumu; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Matsumoto, Takeshi; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Taguchi, Akira; Noma, Kensuke; Higashi, Yukihito

2014-01-01

 Poor oral health is an independent predictor of cardiovascular outcome. Endothelial dysfunction is the initial step of atherosclerosis, resulting in cardiovascular outcomes; but there is no information on the association between oral health and endothelial function. The purpose of this study was to determine the relationships between oral health and endothelial function.  A total of 190 subjects who underwent health examinations (mean age, 57±18 years), including patients with cardiovascular disease, completed a questionnaire on oral health and frequency of tooth brushing, and underwent measurement of vascular function, flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation. The subjects were divided into 2 groups according to frequency of tooth brushing (≥twice/day and

Elimination of Toxic Materials and Solvents from Solid Propellant Compositions

DTIC Science & Technology

2001-01-01

ratio of nitrogen, hydrogen , and oxygen atoms which yield exhaust products that are environmentally benign. Through leveraging with three subsequent...qualification costs make transition to new formulations prohibitive. Therefore, more likely candidates for these new formulations are weapon systems of...facility in place a technology was sought out to treat the nitroglycerin vapors that are emitted. One such technology was photocatalysis of the

Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

PubMed Central

Daiber, Andreas; Oelze, Matthias; Wenzel, Philip; Bollmann, Franziska; Pautz, Andrea; Kleinert, Hartmut

2012-01-01

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/– mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy. PMID:22506100

Enhancement of Tumor-Targeted Delivery of Bacteria with Nitroglycerin Involving Augmentation of the EPR Effect.

PubMed

Fang, Jun; Long, Liao; Maeda, Hiroshi

2016-01-01

The use of bacteria, about 1 μm in size, is now becoming an attractive strategy for cancer treatment. Solid tumors exhibit the enhanced permeability and retention (EPR) effect for biocompatible macromolecules such as polymer-conjugated anticancer agents, liposomes, and micelles. This phenomenon permits tumor-selective delivery of such macromolecules. We report here that bacteria injected intravenously evidenced a property similar to that can of these macromolecules. Bacteria that can accumulate selectively in tumors may therefore be used in cancer treatment.Facultative or anaerobic bacteria will grow even under the hypoxic conditions present in solid tumors. We found earlier that nitric oxide (NO) was among the most important factors that facilitated the EPR effect via vasodilatation, opening of endothelial cell junction gaps, and increasing the blood flow of hypovascular tumors. Here, we describe the augmentation of the EPR effect by means of nitroglycerin (NG), a commonly used NO donor, using various macromolecular agents in different tumor models. More importantly, we report that NG significantly enhanced the delivery of Lactobacillus casei to tumors after intravenous injection of the bacteria, more than a tenfold increase in bacterial accumulation in tumors after NG treatment. This finding suggests that NG has a potential advantage to enhance bacterial therapy of cancer, and further investigations of this possibility are warranted.

49 CFR 173.304a - Additional requirements for shipment of liquefied compressed gases in specification cylinders.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., carbon bisulfide (disulfide), ethyl chloride, ethylene oxide, nickel carbonyl, spirits of nitroglycerin...; DOT-3B400; DOT-4AA480; DOT-4B400; DOT-4BA400; DOT-4BW400; DOT-3E1800; DOT-39; DOT-3AL400. Carbon...; DOT-3T1800; DOT-3HT2000; DOT-39; DOT-3AL1800. Carbon dioxide, refrigerated liquid (see paragraph (e...

49 CFR 173.304a - Additional requirements for shipment of liquefied compressed gases in specification cylinders.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., carbon bisulfide (disulfide), ethyl chloride, ethylene oxide, nickel carbonyl, spirits of nitroglycerin...; DOT-3B400; DOT-4AA480; DOT-4B400; DOT-4BA400; DOT-4BW400; DOT-3E1800; DOT-39; DOT-3AL400. Carbon...; DOT-3T1800; DOT-3HT2000; DOT-39; DOT-3AL1800. Carbon dioxide, refrigerated liquid (see paragraph (e...

Phase I/II Trial of Epothilone Analog BMS-247550, Mitoxantrone, and Prednisone in HRPC Patients Previously Treated with Chemotherapy

DTIC Science & Technology

2006-07-01

McGaw AccuPro Pump Nitroglycerine IV Set (Catalog #V8333) • Clintec IV Fat Emulsion Set (Catalog #2C1105) Filter extension set (to be used with IV sets...menses; libido; vaginitis Vascular – thrombosis/ embolism ; vascular access complication Note: BMS-247550 in combination with other agents could cause...osteoporosis, vertebral compression fractures , pancreatitis, esophagitis, peptic ulcer, dermatologic disturbances, convulsions, vertigo, headache

Tocolysis for management of retained placenta.

PubMed

Abdel-Aleem, Hany; Abdel-Aleem, Mahmoud A; Shaaban, Omar M

2011-01-19

Retained placenta affects 0.5% to 3% of women following delivery, with considerable morbidity if left untreated. Use of tocolytics, either alone or in combination with uterotonics, may be of value to minimise the need for manual removal of the placenta in theatre under anaesthesia. Evaluate the benefits and harms of tocolytics alone or in addition to uterotonics in the management of retained placenta in order to reduce the need for manual removal of placenta. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2010) and contacted experts in the field. Any adequately randomised controlled trial (RCT) comparing the use of tocolytics, either alone or in combination with uterotonics, with no intervention or with other interventions in the management of retained placenta. All women having a vaginal delivery with a retained placenta, regardless of the management of the third stage of labour (expectant or active). We included all trials with haemodynamically stable women in whom the placenta was not delivered at least within 15 minutes after delivery of the baby. Two review authors independently assessed trial quality and extracted data. Consultation of the third author was done if needed. We included one RCT (involving 24 women). It compared the use of nitroglycerin tablets versus placebo after the treatment with oxytocin failed. There was a statistically significant reduction in the need for manual removal of placenta (risk ratio (RR) 0.04, 95% confidence interval (CI) 0.00 to 0.66). There was also a statistically significant reduction in mean blood loss during the third stage of labour (mean difference (MD) -262.50 ml, 95% CI -364.95 to -160.05). Sublingual nitroglycerin caused some haemodynamic changes as it lowers the systolic blood pressure and diastolic blood pressure by a means of 6 and 5 mmHg respectively. Pulse rate increased by a mean of two beats per minute. Sublingual nitroglycerin, given when oxytocin fails, seems to reduce both the need for manual removal of placenta and blood loss during the third stage of labour when compared to placebo. Further trials are needed to confirm its clinical role and safety. Its routine use cannot be recommended based on a single small study. There is no evidence available for other types of tocolytics.

N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo.

PubMed

Creager, M A; Roddy, M A; Boles, K; Stamler, J S

1997-02-01

Nitric oxide forms complexes with an array of biomolecular carriers that retain biological activity. This reactivity of nitric oxide in physiological systems has led to some dispute as to whether endothelium-derived relaxing factors nitric oxide or a closely related adduct thereof, such as a nitrosothiol. In vitro bioassays used to address this question are limited by the exclusion of biological thiols that are requisite for nitrosothiol formation. Thus, the purpose of this study was to obtain insight into the identity of endothelium-derived relaxing factor in vivo. We reasoned that if endothelium-derived relaxing factor in nitric oxide, infusion of physiological concentrations of thiol would potentiate its bioactivity by analogy with effects seen in vitro, whereas nitrosothiol would be resistant to such modulation. We used venous-occlusion plethysmography to study forearm blood flow in normal subjects. Methacholine (0.3 to 10 micrograms/min) and nitroglycerin (1 to 30 micrograms/min) were infused via the brachial artery to elicit endothelium-dependent and endothelium-independent vasodilation, respectively. Dose-response determinations were made for each drug before and after an intra-arterial infusion of the reduced thiol, N-acetylcysteine, at rates estimated to achieve a physiological concentration of 1 mmol/L. Methacholine increased forearm blood flow in a dose-dependent manner. Infusion of N-acetylcysteine did not change the sensitivity (ED50, 1.7 versus 1.7 micrograms/min, P = NS) or maximal response to methacholine. In contrast, thiol increased the sensitivity to nitroglycerin (ED50, 4.7 versus 2.8 micrograms/min, P < .01). Thus, conflicting with reports in vitro, thiol does not modulate endothelium-derived relaxing factor responses in vivo. These data indicate that sulfhydryl groups are not a limiting factor for endothelium-derived relaxing factor responses in forearm resistance vessels in normal humans and are in keeping with reports that nitrosothiol contributes to endothelium-derived relaxing factor bioactivity in plasma and vascular smooth muscle. Potentiation of the effects of nitroglycerin by N-acetylcysteine can be attributed to its enhanced biotransformation to an endothelium-derived relaxing factor equivalent, such as nitrosothiol. These observations support the notion of an equilibrium between nitric oxide and nitrosothiol in biological systems that may be influenced by redox state.

Degradation of TATP, TNT, and RDX using mechanically alloyed metals

NASA Technical Reports Server (NTRS)

Geiger, Cherie (Inventor); Sigman, Michael (Inventor); Fidler, Rebecca (Inventor); Clausen, Christian (Inventor)

2012-01-01

Bimetallic alloys prepared in a ball milling process, such as iron nickel (FeNi), iron palladium (FePd), and magnesium palladium (MgPd) provide in situ catalyst system for remediating and degrading nitro explosive compounds. Specifically, munitions, such as, 2,4,6-trinitrotoluene (TNT), cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), nitrocellulose and nitroglycerine that have become contaminants in groundwater, soil, and other structures are treated on site to remediate explosive contamination.

Modified-release ointment with nitroglycerin β-cyclodextrin inclusion complex for treatment of anal fissures.

PubMed

Centkowska, Katarzyna; Sznitowska, Malgorzata

2013-10-01

The aim was to evaluate ointments for local treatment of anal fissures. Nitroglycerin (NTG) was complexed with β-cyclodextrin (β-CD) to provide prolonged NTG release, with the intention of decreasing systemic drug absorption and thus reducing side effects. Gels, creams and anhydrous water-emulsifying (AWE) ointment with NTG-CD were compared with preparations containing uncomplexed NTG (diluted with crospovidone, NTG-cP). The in-vitro NTG release and ex-vivo skin absorption were studied. The prolonged-release ointment with the NTG-CD complex was formulated using AWE base or w/o cream (20% water); release of NTG from a hydrogel was very fast with both the complexed and uncomplexed forms. From the AWE ointment base, 16.4% or 4.5% of the total NTG dose was released after 6 h when NTG-cP or NTG-CD was incorporated, respectively. With the complexed form, NTG absorption to the skin after a 5-h application was 18.1 or 11.1 μg/g from AWE ointment or cream, respectively; absorption of the uncomplexed NTG was higher: 52.3 or 21.9 μg/g from AWE ointment and cream, respectively. Complexation with β-CD results in prolonged release of NTG from AWE ointment and w/o cream, which was confirmed by the ex-vivo skin absorption results. © 2013 Royal Pharmaceutical Society.

Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes-induced foot ulcer.

PubMed

Hotkar, Mukesh S; Avachat, Amelia M; Bhosale, Sagar S; Oswal, Yogesh M

2015-04-01

Nitroglycerin (NTG) is an organic nitrate rapidly denitrated by enzymes to release free radical nitric oxide and shows improved wound healing and tissue protection from oxidative damage. The purpose of this study was to evaluate whether topical application of NTG in the form of gel/ointment along with a natural wound healing agent, aloe vera, would bring about wound healing by using diabetes-induced foot ulcer model and rat excision wound model. All these formulations were evaluated for pH, viscosity, drug content and ex vivo diffusion studies using rat skin. Based on ex vivo permeation studies, the formulation consisting of carbopol 974p as a gelling agent and aloe vera was found to be suitable. The in vivo study used streptozotocin-induced diabetic foot ulcer and rat excision wound models to analyse wound healing activity. The wound size in animals of all treated groups was significantly reduced compared with that of the diabetic control and marketed treated animals. This study showed that the gel formed with carbopol 974p (1%) and aloe vera promotes significant wound healing and closure in diabetic rats compared with the commercial product and provides a promising product to be used in diabetes-induced foot ulcer. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Phospholemman does not participate in forskolin-induced swine carotid artery relaxation.

PubMed

Meeks, M K; Han, S; Tucker, A L; Rembold, C M

2008-01-01

Phosphorylation of phospholemman (PLM) on ser68 has been proposed to at least partially mediate cyclic AMP (cAMP) mediated relaxation of arterial smooth muscle. We evaluated the time course of the phosphorylation of phospholemman (PLM) on ser68, myosin regulatory light chains (MRLC) on ser19, and heat shock protein 20 (HSP20) on ser16 during a transient forskolin-induced relaxation of histamine-stimulated swine carotid artery. We also evaluated the dose response for forskolin- and nitroglycerin-induced relaxation in phenylephrine-stimulated PLM-/- and PLM+/+ mice. The time course for changes in ser19 MRLC dephosphorylation and ser16 HSP20 phosphorylation was appropriate to explain the forskolin-induced relaxation and the recontraction observed upon washout of forskolin. However, the time course for changes in ser68 PLM phosphorylation was too slow to explain forskolin-induced changes in force. There was no difference in the phenylephrine contractile dose response or in forskolin-induced relaxation dose response observed in PLM-/- and PLM+/+ aortae. In aortae precontracted with phenylephrine, nitroglycerin induced a slightly, but significantly greater relaxation in PLM-/- compared to PLM+/+ aortae. These data are consistent with the hypothesis that ser19 MRLC dephosphorylation and ser16 HSP20 phosphorylation are involved in forskolin-induced relaxation. Our data suggest that PLM phosphorylation is not significantly involved in forskolin-induced arterial relaxation.

Effect of different dosages of nitroglycerin infusion on arterial blood gas tensions in patients undergoing on- pump coronary artery bypass graft surgery.

PubMed

Masoumi, Gholamreza; Pour, Evaz Hidar; Sadeghpour, Ali; Ziayeefard, Mohsen; Alavi, Mostapha; Anbardan, Sanam Javid; Shirani, Shahin

2012-02-01

On-pump coronary artery bypass graft (CABG) surgery impairs gas exchange in the early postoperative period. The main object on this study was evaluation of changes in arterial blood gas values in patients underwent on pump CABG surgery receiving different dose of intravenous nitroglycerin (NTG). sixty-seven consecutive patients undergoing elective on-pump CABG randomly enrolled into three groups receiving NTG 50 μg/min (Group N1, n =67), 100 μg/min (Group N2, n = 67), and 150 μg/min (Group N3, n = 67). Arterial blood gas (ABG) tensions were evaluated just before induction of anesthesia, during anesthesia, at the end of warming up period, and 6 h after admission to the intensive care unit. Pao2 and PH had the highest value during surgery in Group N1, Group N2, and Group N3. No significant difference was noted in mean values of Pao2 and PH during surgery between three groups (P > 0.05). There was no significant difference in HCO3 values in different time intervals among three groups (P > 0.05). our results showed that infusing three different dosage of NTG (50, 100, and 150 μg/min) had no significant effect on ABG tensions in patients underwent on-pump CABG surgery.

Evaluation of nitroglycerin effect on remote photoplethysmogram waveform acquired at green and near infra-red illumination

NASA Astrophysics Data System (ADS)

Marcinkevics, Z.; Rubins, U.; Caica, A.; Grabovskis, A.

2017-12-01

Assessment of skin microcirculation provides diagnostically valuable information during the early stages of pathologies. The simple, cost-effective and intrusive alternative to existing circulation assessment methods is remote photoplethysmography (rPPG). The objective of the present pilot study was to reveal an effect on sublingual administration of 1 mg nitroglycerin on systemic hemodynamic parameters and rPPG waveforms, at 810 nm and 530nm illumination. The protocol comprised 3 minutes of baseline recording, 15 minutes recording of NTG effect, 2 minutes of arterial occlusion and the following 3 min reactive hyperemia. Two PPG signals were acquired from glabrous skin of the middle finger distal phalange, consecutively at 530 nm and 810nm, 125 fps per channel, and systemic cardiovascular parameters were continuously registered in a beat-to-beat manner with a Finameter-midi system. The NTG effect was observed 0.7- 1.2 minutes post administration, reaching its maximum after 3 minutes. Systemic cardiovascular parameters significantly changed: mean arterial pressure decreased by 7.7+/-3.6%, total peripheral resistance by 10.5+/-9.0%, whereas the heart rate increased by 27.2+/-11.8%. Substantial alterations were observed for rPPG waveforms during NTG effect, decreasing reflection and stiffness indices. It has been concluded that rPPG waveform may provide information related to arterial stiffness, and could be potentially utilized in the clinics.

Aerobic Growth on Nitroglycerin as the Sole Carbon, Nitrogen, and Energy Source by a Mixed Bacterial Culture

PubMed Central

Accashian, John V.; Vinopal, Robert T.; Kim, Byung-Joon; Smets, Barth F.

1998-01-01

Nitroglycerin (glycerol trinitrate [GTN]), an explosive and vasodilatory compound, was metabolized by mixed microbial cultures from aeration tank sludge previously exposed to GTN. Aerobic enrichment cultures removed GTN rapidly in the absence of a supplemental carbon source. Complete denitration of GTN, provided as the sole C and N source, was observed in aerobic batch cultures and proceeded stepwise via the dinitrate and mononitrate isomers, with successive steps occurring at lower rates. The denitration of all glycerol nitrate esters was found to be concomitant, and 1,2-glycerol dinitrate (1,2-GDN) and 2-glycerol mononitrate (2-GMN) were the primary GDN and GMN isomers observed. Denitration of GTN resulted in release of primarily nitrite-N, indicating a reductive denitration mechanism. Biomass growth at the expense of GTN was verified by optical density and plate count measurements. The kinetics of GTN biotransformation were 10-fold faster than reported for complete GTN denitration under anaerobic conditions. A maximum specific growth rate of 0.048 ± 0.005 h−1 (mean ± standard deviation) was estimated for the mixed culture at 25°C. Evidence of GTN toxicity was observed at GTN concentrations above 0.3 mM. To our knowledge, this is the first report of complete denitration of GTN used as a primary growth substrate by a bacterial culture under aerobic conditions. PMID:9726874

Non-hemodynamic effects of organic nitrates and the distinctive characteristics of pentaerithrityl tetranitrate.

PubMed

Gori, Tommaso; Daiber, Andreas

2009-01-01

Organic nitrates are among the oldest and yet most commonly employed drugs in the long-term therapy of coronary artery disease and congestive heart failure. While they have long been used in clinical practice, our understanding of their mechanism of action and side effects remains incomplete. For instance, recent findings provide evidence of previously unanticipated, non-hemodynamic properties that include potentially beneficial mechanisms (such as the induction of a protective phenotype that mimics ischemic preconditioning), but also toxic effects (such as endothelial and autonomic dysfunction, rebound angina, tolerance). To date, the most commonly employed organic nitrates are isosorbide mononitrate, isosorbide dinitrate, and nitroglycerin (glyceryl trinitrate). Another organic nitrate, pentaerithrityl tetranitrate (PETN), has long been employed in eastern European countries and is currently being reintroduced in Western countries. In light of their wide use, and of the (re)introduction of PETN in Western markets, the present review focuses on the novel effects of organic nitrates, describing their potential clinical implications and discussing differences among different compounds. We believe that these recent findings have important clinical implications. Since the side effects of organic nitrates such as nitroglycerin and isosorbides appear to be mediated by reactive oxygen species, care should be taken that drugs with antioxidant properties are co-administered. On the other hand, efforts should be made to clinically exploit the preconditioning effects of these drugs.

Development of an On-animal Separation-based Sensor for Monitoring Drug Metabolism in Freely Roaming Sheep

PubMed Central

Scott, David E.; Willis, Sean D.; Gabbert, Seth; Johnson, Dave A.; Naylor, Erik; Janle, Elsa M.; Krichevsky, Janice E.; Lunte, Craig E.; Lunte, Susan M.

2015-01-01

The development of an on-animal separation-based sensor that can be employed for monitoring drug metabolism in a freely roaming sheep is described. The system consists of microdialysis sampling coupled directly to microchip electrophoresis with electrochemical detection (MD-ME-EC). Separations were accomplished using an all-glass chip with integrated platinum working and reference electrodes. Discrete samples from the microdialysis flow were introduced into the electrophoresis chip using a flow-gated injection approach. Electrochemical detection was accomplished in-channel using a two-electrode isolated potentiostat. Nitrite was separated by microchip electrophoresis using reverse polarity and a run buffer consisting of 50 mM phosphate at pH 7.4. The entire system was under telemetry control. The system was first tested with rats to monitor the production of nitrite following introduction of nitroglycerin into the subdermal tissue using a linear probe. The data acquired using the on-line MD-ME-EC system was compared to that obtained off-line analysis by liquid chromatography with electrochemical detection (LC-EC), using a second microdialysis probe implanted parallel to the first probe in the same animal. The MD-ME-EC device was then used on-animal to monitor the subdermal metabolism of nitroglycerin in sheep. The ultimate goal is to use this device to simultaneously monitor drug metabolism and behavior in a freely roaming animal. PMID:25697221

Nitroglycerin for management of retained placenta.

PubMed

Abdel-Aleem, Hany; Abdel-Aleem, Mahmoud A; Shaaban, Omar M

2015-11-12

Retained placenta affects 0.5% to 3% of women following delivery, with considerable morbidity if left untreated. Use of nitroglycerin (NTG), either alone or in combination with uterotonics, may be of value to minimise the need for manual removal of the placenta in theatre under anaesthesia. To evaluate the benefits and harms of NTG as a tocolytic, either alone or in addition to uterotonics, in the management of retained placenta. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2015), reference lists of retrieved studies and contacted experts in the field. Any adequately randomised controlled trial (RCT) comparing the use of NTG, either alone or in combination with uterotonics, with no intervention or with other interventions in the management of retained placenta. All women having a vaginal delivery with a retained placenta, regardless of the management of the third stage of labour (expectant or active). We included all trials with haemodynamically stable women in whom the placenta was not delivered at least within 15 minutes after delivery of the baby. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We included three randomised controlled trials (RCTs) with 175 women. The three published RCTs compared NTG alone versus placebo. The detachment status of retained placenta was unknown in all three RCTs. Collectively, among the three included trials, two were judged to be at low risk of bias and the third trial was judged to be at high risk of bias for two domains: incomplete outcome data and selective reporting. The three trials reported seven out of 23 of the review's pre-specified outcomes.The primary outcome "manual removal of the placenta" was reported in all three studies. No differences were seen between NTG and placebo for manual removal of the placenta (average risk ratio (RR) 0.83, 95% confidence interval (CI) 0.47 to 1.46; women = 175; I² = 81%). A random-effects model was used because of evidence of substantial heterogeneity in the analysis. There were also no differences between groups for risk of severe postpartum haemorrhage (RR 0.93, 95% CI 0.62 to 1.39; women = 150; studies = two; I² = 0%). Blood transfusion was only reported in one study (40 women) and again there was no difference between groups (RR 1.00, 95% CI 0.07 to 14.90; women = 40; I² = 0%). Mean blood loss (mL) was reported in the three studies and no differences were observed (mean difference (MD) -115.31, 95% CI -306.25 to 75.63; women = 169; I² = 83%). Nitroglycerin administration was not associated with an increase in headaches (RR 1.09, 95% CI 0.80 to 1.47; women = 174; studies = three; I² = 0%). However, nitroglycerin administration was associated with a significant, though mild, decrease in systolic and diastolic blood pressure and a significant increase in pulse rate (MD -3.75, 95% CI -7.47 to -0.03) for systolic blood pressure, and (MD 6.00, 95% CI 3.07 to 8.93) for pulse rate (beats per minute) respectively (reported by only one study including 24 participants). Maternal mortality and addition of therapeutic uterotonics were not reported in any study. In cases of retained placenta, currently available data showed that the use of NTG alone did not reduce the need for manual removal of placenta. This intervention did not increase the incidence of severe postpartum haemorrhage nor the need for blood transfusion. Haemodynamically, NTG had a significant though mild effect on both pulse rate and blood pressure.

O-Raffinose Crosslinking Substantially Ameliorates the Vasoconstrictive and Nitric-Oxide-Inactivating Effects of Unmodified Human Hemoglobin in the Rat

DTIC Science & Technology

1997-07-11

severity of the increase in MAP and SVR is accounted for by the profound depressant effect of Ao SFH on cardie output (Table III). We have not examined...1985. N- acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin. / Clin Invest 76:703-708. 34. Mendelsohn, M., S. O’Neill...D. George, and J. Loscalzo. 1990. Inhibition of fibrinogen binding to human platelets by S-nitroso-N- acetylcysteine . / Biol Chem 265:19028-19034. 27

Pharmacological interventions to treat phlebitis: systematic review.

PubMed

dos Reis, Paula Elaine Diniz; Silveira, Renata Cristina de Campos Pereira; Vasques, Christiane Inocêncio; de Carvalho, Emilia Campos

2009-01-01

This study presents a systematic review for evaluating effective pharmacological actions for the treatment of phlebitis stemming from infusion therapy. The studies reviewed were categorized according to the type of therapeutic approach proposed by the author and by the level of evidence presented. The review found that topical nitroglycerin and notoginseny were more effective in the reduction of the inflammatory process when compared with other proposed alternatives. Nevertheless, the development of research related to possible alternatives for the treatment of phlebitis is important.

Applied Innovative Technologies for Characterization of Nitrocellulose and Nitroglycerin Contaminated Buildings and Soils

DTIC Science & Technology

2008-07-01

analyses of the NG test group samples are summarized in Table 4- 8 along with results for the lab reference method, STL (SW- 846 ) Method 8330. The results for...Drive, Suite 17D08,Alexandria,VA,22350-3605 8 . PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10...Standard Form 298 (Rev. 8 -98) Prescribed by ANSI Std Z39-18 i COST & PERFORMANCE REPORT Project: ER-0130 TABLE OF CONTENTS Page 1.0 EXECUTIVE

History of the Shaped Charge Effect: The First 100 Years

DTIC Science & Technology

1990-03-22

patent, wave shapers, follow-through, U.S. 1949 39 6.5-in. ATAR HEAT rocket, U.S. NOTS, 1950 (schematic) 40 Test of 15-in. long standoff shaped charge...Swiss chemist Frederick Schoenbein in 1845, and nitroglycerin, derived by Ascanio Sobrero, professor of Chemistry at the University of Turin, Italy, in...totally new warhead and fuze system and delivery of the first 1000 rounds to Korea in less than 20 days! The 6.5-Inch ATAR (Code Name "RAM") The 6.5

Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance.

PubMed

Thadani, Udho

2014-08-01

Nitrate therapy has been an effective treatment for ischemic heart disease for over 100 years. The anti-ischemic and exercise-promoting benefits of sublingually administered nitrates are well established. Nitroglycerin is indicated for the relief of an established attack of angina and for prophylactic use, but its effects are short lived. In an effort to increase the duration of beneficial effects, long-acting orally administered and topical applications of nitrates have been developed; however, following their continued or frequent daily use, patients soon develop tolerance to these long-acting nitrate preparations. Once tolerance develops, patients begin losing the protective effects of the long-acting nitrate therapy. By providing a nitrate-free interval, or declining nitrate levels at night, one can overcome or reduce the development of tolerance, but cannot provide 24-h anti-anginal and anti-ischemic protection. In addition, patients may be vulnerable to occurrence of rebound angina and myocardial ischemia during periods of absent nitrate levels at night and early hours of the morning, and worsening of exercise capacity prior to the morning dose of the medication. This has been a concern with nitroglycerin patches but not with oral formulations of isosorbide-5 mononitrates, and has not been adequately studied with isosorbide dinitrate. This paper describes problems associated with nitrate tolerance, reviews mechanisms by which nitrate tolerance and loss of efficacy develop, and presents strategies to avoid nitrate tolerance and maintain efficacy when using long-acting nitrate formulations.

Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues.

PubMed

Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József

2017-01-01

The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening.

Changes of the Carotid Artery Doppler Flow Velocity Pattern after Sublingual Nitroglycerin in Patients with Hypertension

PubMed Central

Jeong, Jin-Won; Park, Ock-Kyu; Park, Yang-Kyu; Tei, Chuwa; Tanaka, Nobuyuki

1998-01-01

Objective To evaluate the applicability of carotid Doppler echography for the assessment of changes of peripheral hemodynamics in the hypertensives. Subjects 28 hypertensives (17 males, 11 females), mean age of 64 yrs and 40 normal controls (24 males, 16 females) mean age of 49 yrs. Methods We recorded the right common carotid arterial Doppler flow velocity (BFV) pattern and measured the peak velocities of the percussion wave (P) and late rising tidal wave (T), the ratio of the two (P/T), the time interval between the two peaks corrected by heart rate (P-Tc), systolic flow velocity integral (FVI) and carotid artery diameter (CAD) before and after 0.4 mg dose of subligual nitroglycerin (NTG). Results 1) In hypertensives, the P wave velocity showed lower and P-Tc interval shorter than those of the normal controls at baseline. 2) After NTG, the P-Tc and P/T increased, but the T and FVI decreased significantly in both groups of subjects. 3) The P/T ratio was less significantly increased after NTG in the hypertensives than in the controls. These results suggest that NTG might have been involved in concomitant reduction and delay of the wave reflection from the peripheral vessels, preferentially in the normal subjects than in hypertensives. Concluson The carotid Doppler echography can be useful for the evaluation of the changes of hemodynamics in the peripheral vessel such as carotid artery in hypertensive subjects. PMID:9538627

Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues

PubMed Central

Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József

2017-01-01

Background The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. Materials and methods In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. Results The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. Discussion The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening. PMID:28053504

Effect of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin in patients with heart failure

PubMed Central

Zhang, Sijie; Wang, Zhiqian

2016-01-01

Abstract Background: This study was the first to evaluate the therapeutic outcomes of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin (NIT) in patients with heart failure (HF). Methods: The electronic databases were systematically searched to identify available studies. The pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs) were analyzed to assess the mortality, readmission, hypotension, and renal dysfunction in the comparison of rhBNP and NIT therapies. Results: Final 5 randomized controlled trials (RCTs) involving 782 patients with HF were carried out in our study. The pooled OR of mortality, readmission, and hypotension showed that no significant difference was found in both drugs (P > 0.05), with the absence of heterogeneity. The incidence of renal dysfunction was not significant difference in both groups (P = 0.85). The pooled OR from 2 studies of Asian population using multivariate analysis demonstrated that the use of rhBNP was correlated with a significantly decreased risk of renal dysfunction (I2 = 0.0%, OR = 0.19, P = 0.001). Possible publication bias was not detected using Egger's test (P > 0.05). Conclusions: The results suggested that rhBNP and NIT therapies were not significant difference in mortality, readmission, and hypotension. The use of rhBNP may become a useful predictor of renal dysfunction in Asian patients with HF. Additional studies are needed for Caucasian population with HF. PMID:27858837

Nitroglycerin degradation mediated by soil organic carbon under aerobic conditions.

PubMed

Bordeleau, Geneviève; Martel, Richard; Bamba, Abraham N'Valoua; Blais, Jean-François; Ampleman, Guy; Thiboutot, Sonia

2014-10-01

The presence of nitroglycerin (NG) has been reported in shallow soils and pore water of several military training ranges. In this context, NG concentrations can be reduced through various natural attenuation processes, but these have not been thoroughly documented. This study aimed at investigating the role of soil organic matter (SOM) in the natural attenuation of NG, under aerobic conditions typical of shallow soils. The role of SOM in NG degradation has already been documented under anoxic conditions, and was attributed to SOM-mediated electron transfer involving different reducing agents. However, unsaturated soils are usually well-oxygenated, and it was not clear whether SOM could participate in NG degradation under these conditions. Our results from batch- and column-type experiments clearly demonstrate that in presence of dissolved organic matter (DOM) leached from a natural soil, partial NG degradation can be achieved. In presence of particulate organic matter (POM) from the same soil, complete NG degradation was achieved. Furthermore, POM caused rapid sorption of NG, which should result in NG retention in the organic matter-rich shallow horizons of the soil profile, thus promoting degradation. Based on degradation products, the reaction pathway appears to be reductive, in spite of the aerobic conditions. The relatively rapid reaction rates suggest that this process could significantly participate in the natural attenuation of NG, both on military training ranges and in contaminated soil at production facilities. Copyright © 2014 Elsevier B.V. All rights reserved.

The association between nitroglycerin use and adverse outcomes in women undergoing cesarean delivery in the second stage of labor.

PubMed

Isquick, Sarah; Henry, Dana; Nakagawa, Sanae; Moghadassi, Michelle; Thiet, Mari-Paule; Norton, Mary; Lucero, Jennifer

2017-06-01

To identify predictors of hysterotomy extension in women undergoing cesarean delivery (CD) in the second stage of labor, and whether use of nitroglycerin (NTG) during CD has a protective effect. We conducted a retrospective cohort study of women undergoing CD in the second stage of labor from 2012 to 2015. Some women received NTG at the obstetrician's request. Logistic regression was used to examine the relationship between second stage duration and NTG administration on maternal and neonatal outcomes. Of the 391 women in the sample, 27% had an extension and 12% received NTG. Second stage ≥4 h was associated with a 2.14-fold higher risk of extension (95% CI 1.22-3.75), a 2.00-fold higher risk of hemorrhage (95% CI: 1.20-3.33) and 2.42-fold higher risk of blood transfusion during delivery hospitalization (95% CI: 0.99-5.91). Intravenous (IV) and sublingual-spray (SL-spray) NTG administration were not associated with an increased risk of hemorrhage or extension. SL-NTG was associated with 4.68-fold increased odds of 5-min Apgar <7 (95% CI 1.42-15.41) and 3.36-fold greater odds of NICU admission (95% CI 1.20-9.41). We found no evidence that NTG protects against extension, and SL-NTG use was associated with adverse neonatal outcomes. Clinical trials should be conducted to evaluate risk and benefits of NTG use.

Comparison of the relaxation effect in vitro of nitroglycerin vs. fenoterol on human myometrial strips.

PubMed

David, M; Hamann, C; Chen, F C; Bruch, L; Lichtenegger, W

2000-01-01

Substance dose-related comparison of relaxation effect of nitroglycerin (GTN) and the beta 2-mimetic substance fenoterol in human myometrial tissue. Test criterion is the isometric force development of isolated human myometrial strips. These muscle strips were removed from the lower uterine segment at cesarean section. Fenoterol in concentrations of 3 x 10(-8)-10(-5) mol/l or GTN in concentrations of 1.7 x 10(-8)-5.8 x 10(-4) mol/l were applied to the 2 x 2 x 10-mm strips, which were fixed and maintained in tissue baths. The curves were plotted on line. The integral or the "area under the curve" (AUC) served as the parameter for muscle strip activity. A total of 100 strips from 20 patients were used. GTN demonstrated a significant relaxation effect in the in vitro model on human myometrial strips from pregnant women already treated with oxytocin. The effect was able to be enhanced to a point where oxytocin-induced contractions were completely absent. A relatively clear connection was demonstrated between dose and effect whereby increased muscle relaxation resulted at increased concentrations. Compared to GTN application, muscle strip relaxation was less pronounced under fenoterol; a complete inhibition of myometrial activity was not achieved under fenoterol. With respect to relaxation of the myometrial tissue samples the NO donor GTN is at least as potent as the standard tocolytic agent fenoterol in the in vitro model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moroz, B.B.; Grozdou, S.P.

Electrocardiographic data are presented on the reaction of the myocardium to adrenaline, carbocholine, ephedrin, and nitroglycerin in rabbits at different stages of acute radiation sickness induced by polonium. There were divulged changes in the excitability and conductivity of the myocardium in which two developmental stages could be distinguished. In the first stage the sensitivity of the heart was elevated. After the introduction of adrenaline, bradycardia intensified, exrasystoles were observed more often and ventricular flutter and heterotopic ventricular rhythm. was observed. The administration of carbocholine produced a sharper retardation of atrioventricular conductivity, even an incomplete block of the II to IIImore » degree, etc. In the second stage, as compared with the early periods of radiation sickness, a drop of cardiac sensitivity was observed. The reactivity of the heart to adrenaline, carbocholine, and nitroglycerin, especially at late stages, was considerably reduced or the myocardial reaction was absent completely. At the peak of radiation sickness marked changes of the electrocardiogram were seen which were indicative of dystrophic processes in the myocardium (a drop of the wave P amplitude and QRS complex, a rise and a sharpening of T wave a lengthening of the QRST complex, and displacement of the isoelectric axis to the right). An elevated sensitivity of the heart during the first stage was apparently associated with disturbances of extracardiac innervation, especially with the increase of parasympathetic influences. A diminution of the cardiac reaction in the second stage was possibly due to a weakening of extracardiac reflexes and affection of the cardiac muscle as well. (auth)« less

Nitroglycerin-mediated, but not flow-mediated vasodilation, is associated with blunted nocturnal blood pressure fall in patients with resistant hypertension.

PubMed

Fontes-Guerra, Priscila C A; Cardoso, Claudia R L; Muxfeldt, Elizabeth S; Salles, Gil F

2015-08-01

Endothelial function by flow-mediated (FMD) and nitroglycerin-mediated vasodilations (NMD) was scarcely investigated in resistant hypertension. We aimed to assess the independent correlates of FMD and NMD in resistant hypertensive patients, particularly their associations with ambulatory blood pressures (BP) and nocturnal BP fall patterns. In a cross-sectional study, 280 resistant hypertensive patients performed 24-h ambulatory BP monitoring, carotid-femoral pulse wave velocity, polysomnography, and brachial artery FMD and NMD by high-resolution ultrasonography. Independent correlates of FMD, NMD, and brachial artery diameter (BAD) were assessed by multiple linear and logistic regressions. Median (interquartile range) FMD was 0.75% (-0.6 to +4.4%) and NMD was 11.8% (7.1-18.4%). Baseline BAD and diabetes were independently associated with both FMD and NMD. Older age and prior cardiovascular diseases were associated with altered FMD, whereas higher night-time SBP and lower nocturnal SBP fall were associated with impaired NMD. Moreover, there was a significant gradient of impaired NMD according to blunted nocturnal BP decline patterns. BAD was independently associated with age, sex, BMI, albuminuria, and nocturnal SBP fall. Further adjustments to blood flow velocity, aortic stiffness, plasma aldosterone concentration, and sleep apnea did not change these relationships. NMD, but not FMD, is independently associated with unfavorable night-time BP levels and nondipping patterns, and may be a better cardiovascular risk marker in patients with resistant hypertension. BAD also may provide additional prognostic information.

Effect of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin in patients with heart failure: A systematic review and meta-analysis.

PubMed

Zhang, Sijie; Wang, Zhiqian

2016-11-01

This study was the first to evaluate the therapeutic outcomes of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin (NIT) in patients with heart failure (HF). The electronic databases were systematically searched to identify available studies. The pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs) were analyzed to assess the mortality, readmission, hypotension, and renal dysfunction in the comparison of rhBNP and NIT therapies. Final 5 randomized controlled trials (RCTs) involving 782 patients with HF were carried out in our study. The pooled OR of mortality, readmission, and hypotension showed that no significant difference was found in both drugs (P > 0.05), with the absence of heterogeneity. The incidence of renal dysfunction was not significant difference in both groups (P = 0.85). The pooled OR from 2 studies of Asian population using multivariate analysis demonstrated that the use of rhBNP was correlated with a significantly decreased risk of renal dysfunction (I = 0.0%, OR = 0.19, P = 0.001). Possible publication bias was not detected using Egger's test (P > 0.05). The results suggested that rhBNP and NIT therapies were not significant difference in mortality, readmission, and hypotension. The use of rhBNP may become a useful predictor of renal dysfunction in Asian patients with HF. Additional studies are needed for Caucasian population with HF.

Peripheral Sensory Neurons Expressing Melanopsin Respond to Light

PubMed Central

Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping; Blixt, Frank W.; Parikh, Sachin; Kessler, Jason; Pérez de Sevilla Müller, Luis; Habib, Samer; Kim, Paul; Wang, Zhe Z.; Rodriguez, Allen; Charles, Andrew; Nusinowitz, Steven; Edvinsson, Lars; Barnes, Steven; Brecha, Nicholas C.; Gorin, Michael B.

2016-01-01

The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior. PMID:27559310

New approaches to prevention and treatment of radial artery graft vasospasm.

PubMed

Cable, D G; Caccitolo, J A; Pearson, P J; O'Brien, T; Mullany, C J; Daly, R C; Orszulak, T A; Schaff, H V

1998-11-10

There has been renewed interest in radial artery (RA) conduits for coronary artery bypass because of the relative resistance of arterial grafts to atherosclerosis compared with autogenous vein grafts. Although improved drug therapy for arterial spasm is now available, vasospasm still occurs in at least 5% to 10% of RA grafts. We systematically evaluated the effectiveness of calcium channel blockers and organic nitrates for inhibition or reversal of RA contraction in vitro. Additionally, we investigated the efficacy of novel gene therapy with endothelial nitric oxide synthase (eNOS) to inhibit RA contractions. Segments of RA from 28 patients undergoing coronary artery bypass grafting were mounted in organ chambers. In control experiments, KCl (5 to 50 mmol/L) produced dose-dependent increases in tension (maximum tension, 14.3 +/- 3.0 g, n = 7). Addition of diltiazem or verapamil had no significant effect on KCl contraction (128 +/- 36% and 88 +/- 24% control, respectively); however, nifedipine markedly inhibited KCl contraction (27 +/- 4% control, P = 0.005). Norepinephrine (NE, 10(-9) to 10(-4) M) produced dose-dependent increases in tension (maximum tension, 15.7 +/- 2.7 g in control rings, n = 8). Diltiazem and verapamil pretreatment had no significant effect on NE contraction (103 +/- 14% and 90 +/- 14% control, respectively); nifedipine significantly inhibited NE contraction (70 +/- 11% control, P = 0.02). Isosorbide dinitrate and nitroglycerin markedly inhibited KCl contractions (47 +/- 9% and 30 +/- 8% of controls, n = 6) and NE contractions (42 +/- 10% and 31 +/- 9% of controls, n = 6). Nifedipine, isosorbide, and nitroglycerin were further evaluated for the ability to reverse an established contraction (KCl 40 mmol/L); nitroglycerin was most effective in reversing RA contraction. In separate experiments, RA underwent adenoviral-mediated gene transfer with vehicle, Escherichia coli beta-galactosidase, or eNOS (eNOS, 10(10) PFU/mL x 1 hour). Transgene expression was confirmed by beta-galactosidase activity and eNOS immunohistochemistry after 40 hours of ex vivo incubation. Immunohistochemistry demonstrated recombinant NOS in adenovirus encoding bovine eNOS (Ad.CMVeNOS) RA only. Ad.CMVeNOS arteries contracted only 46.6 +/- 13.7% of controls to KCl (n = 5) and 48.2 +/- 11.4% of controls to prostaglandin F2 alpha a (10(-9) to 10(-6) M, n = 5). Diltiazem, which is used empirically to prevent RA vasospasm, had little effect on human RA contractions (receptor-independent and receptor-dependent). Organic nitrates inhibited and reversed RA contractions. Adenoviral transfer of NOS suggests that future clinical application of gene therapy may play an important role in prevention of RA vasospasm.

Symptoms, adverse effects, and complications associated with dobutamine stress echocardiography. Experience in 1118 patients.

PubMed

Mertes, H; Sawada, S G; Ryan, T; Segar, D S; Kovacs, R; Foltz, J; Feigenbaum, H

1993-07-01

The use of dobutamine stress echocardiography for the evaluation of coronary artery disease is rapidly expanding. New applications of the technique are being investigated in a wide variety of patients including those with advanced coronary artery disease. Despite its widespread use, the safety of dobutamine stress echocardiography has not been sufficiently documented. A consecutive series of 1118 patients undergoing dobutamine stress echocardiography for evaluation of known or suspected coronary artery disease form the basis of this report. Dobutamine stress testing was performed for evaluation of chest pain, risk assessment before noncardiac surgery, after recent myocardial infarction, or as a part of ongoing research protocols. Over the study period, the maximal dose of dobutamine used was increased from 30 to 50 micrograms/kg per minute, and atropine was used in 420 (37%) patients. There were no occurrences of death, myocardial infarction, or episodes of sustained ventricular tachycardia as a result of dobutamine stress testing. The major reasons for test termination were achievement of target heart rate in 583 patients (52.1%), maximum dose in 255 (22.8%), and angina pectoris in 142 (13%). The test was terminated in 36 (3%) patients because of noncardiac side effects including nausea, anxiety, headache, tremor, and urgency. Angina pectoris occurred in 216 (19.3%) patients. Sublingual nitroglycerin, a short-acting beta-blocker, or both types of medication were administered in 80 of these patients for relief of angina pectoris. None required intravenous nitroglycerin. A total of 736 (65%) patients had stable sinus rhythm throughout the test. The most common arrhythmias were frequent premature ventricular complexes (six or more per minute) in 172 patients (15%), and frequent premature atrial complexes in 86 (8%). There were 40 patients with nonsustained ventricular tachycardia. None had symptoms associated with the tachycardia, and only one received specific pharmacological treatment to prevent recurrence of the arrhythmia after the test was terminated. The patients who were evaluated after recent myocardial infarction and those who received atropine did not have a higher frequency of ventricular tachycardia compared with those without recent infarction and those not receiving atropine. Dobutamine stress echocardiography was safely performed using supplemental atropine and an aggressive dosing protocol. Noncardiac side effects were usually minor. Arrhythmias were well tolerated and rarely required treatment. In this study, serious complications from myocardial ischemia did not occur. Symptomatic ischemia was effectively treated with test termination, sublingual nitroglycerin, or short-acting beta-blockers.

Nitroglycerin Attenuates Vasoconstriction of HBOC-201 during Hemorrhagic Shock Resuscitation

DTIC Science & Technology

2010-01-01

A 00 w 484 LM. Katz ec al. / Resuscicacion 81 (2010) 481-487 45 40 35 ~ 30 E 25 E ll . 20 ct ll . 15 :::= 10 5 0 5!o 0 0...criticised for either being too slow or too fast. EMBO Rep 2002;3:14-6. 35. Knudson MM. Lee s. Erickson V, Morabito D, Derugin N, Manley GT. Tissue oxy...vasodilation with nitrocompounds-is there a maximum? Z Kardiol1989;78:38-40. 40. Noonan PK. Williams Rl.. Benet lL Dose dependent pharmacokinetics of

[Usefullness of transesophageal echocardiography in early detection of coronary spasm].

PubMed

Sagara, M; Haraguchi, M; Hamu, Y; Isowaki, S; Yoshimura, N

1996-04-01

Intraoperative transesophageal echocardiography (TEE) was performed on a 62-year-old man who underwent abdominal aortic replacement for abdominal aortic aneurysm under general anesthesia combined with epidural anesthesia. Coronary artery spasm occurred after unexpected massive hemorrhage, and TEE showed hypokinesis in the posterior-inferior left ventricular wall. The changes in TEE preceded the ST elevation in the ECG. Bolus infusion of isosorbide dinitrate and continuous infusion of nitroglycerin alleviated these changes. TEE enabled us to detect and evaluate coronary spasm before the appearance of ST changes in ECG.

Aldehyde dehydrogenase 2 protects human umbilical vein endothelial cells against oxidative damage and increases endothelial nitric oxide production to reverse nitroglycerin tolerance.

PubMed

Hu, X Y; Fang, Q; Ma, D; Jiang, L; Yang, Y; Sun, J; Yang, C; Wang, J S

2016-06-10

Medical nitroglycerin (glyceryl trinitrate, GTN) use is limited principally by tolerance typified by a decrease in nitric oxide (NO) produced by biotransformation. Such tolerance may lead to endothelial dysfunction by inducing oxidative stress. In vivo studies have demonstrated that aldehyde dehydrogenase 2 (ALDH2) plays important roles in GTN biotransformation and tolerance. Thus, modification of ALDH2 expression represents a potentially effective strategy to prevent and reverse GTN tolerance and endothelial dysfunction. In this study, a eukaryotic expression vector containing the ALDH2 gene was introduced into human umbilical vein endothelial cells (HUVECs) by liposome-mediated transfection. An indirect immunofluorescence assay showed that ALDH2 expression increased 24 h after transfection. Moreover, real-time polymerase chain reaction and western blotting revealed significantly higher ALDH2 mRNA and protein expression in the gene-transfected group than in the two control groups. GTN tolerance was induced by treating HUVECs with 10 mM GTN for 16 h + 10 min, which significantly decreased NO levels in control cells, but not in those transfected with ALDH2. Overexpression of ALDH2 increased cell survival against GTN-induced cytotoxicity and conferred protection from oxidative damage resulting from nitrate tolerance, accompanied by decreased production of intracellular reactive oxygen species and reduced expression of heme oxygenase 1. Furthermore, ALDH2 overexpression promoted Akt phosphorylation under GTN tolerance conditions. ALDH2 gene transfection can reverse and prevent tolerance to GTN through its bioactivation and protect against oxidative damage, preventing the development of endothelial dysfunction.

Mechanisms mediating Nitroglycerin-induced Delayed Onset Hyperalgesia in the Rat

PubMed Central

Ferrari, Luiz F.; Levine, Jon D.; Green, Paul G.

2016-01-01

Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN’s very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ~30 min in male and ~45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggest potential novel risk factors and targets for the treatment of migraine. PMID:26779834

Concomitant Intravenous Nitroglycerin With Intracoronary Delivery of AAV1.SERCA2a Enhances Gene Transfer in Porcine Hearts

PubMed Central

Karakikes, Ioannis; Hadri, Lahouaria; Rapti, Kleopatra; Ladage, Dennis; Ishikawa, Kiyotake; Tilemann, Lisa; Yi, Geng-Hua; Morel, Charlotte; Gwathmey, Judith K; Zsebo, Krisztina; Weber, Thomas; Kawase, Yoshiaki; Hajjar, Roger J

2012-01-01

SERCA2a gene therapy improves contractile and energetic function of failing hearts and has been shown to be associated with benefits in clinical outcomes, symptoms, functional status, biomarkers, and cardiac structure in a phase 2 clinical trial. In an effort to enhance the efficiency and homogeneity of gene uptake in cardiac tissue, we examined the effects of nitroglycerin (NTG) in a porcine model following AAV1.SERCA2a gene delivery. Three groups of Göttingen minipigs were assessed: (i) group A: control intracoronary (IC) AAV1.SERCA2a (n = 6); (ii) group B: a single bolus IC injection of NTG (50 µg) immediately before administration of intravenous (IV) AAV1.SERCA2a (n = 6); and (iii) group C: continuous IV NTG (1 µg/kg/minute) during the 10 minutes of AAV1.SERCA2a infusion (n = 6). We found that simultaneous IV infusion of NTG and AAV1.SERCA2a resulted in increased viral transduction efficiency, both in terms of messenger RNA (mRNA) as well as SERCA2a protein levels in the whole left ventricle (LV) compared to control animals. On the other hand, IC NTG pretreatment did not result in enhanced gene transfer efficiency, mRNA or protein levels when compared to control animals. Importantly, the transgene expression was restricted to the heart tissue. In conclusion, we have demonstrated that IV infusion of NTG significantly improves cardiac gene transfer efficiency in porcine hearts. PMID:22215018

Gender Differences in Bed Rest: Preliminary Analysis of Vascular Function

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Stenger, Michael B.; Martin, David S.; Freeman-Perez, Sondra A.; Phillips, Tiffany; Ribeiro, L. Christine

2008-01-01

Orthostatic intolerance is a recognized consequence of spaceflight. Numerous studies have shown that women are more susceptible to orthostatic intolerance following spaceflight as well as bed rest, the most commonly used ground-based analog for spaceflight. One of the possible mechanisms proposed to account for this is a difference in vascular responsiveness between genders. We hypothesized that women and men would have differing vascular responses to 90 days of 6-degree head down tilt bed rest. Additionally, we hypothesized that vessels in the upper and lower body would respond differently, as has been shown in the animal literature. Thirteen subjects were placed in bedrest for 90 days (8 men, 5 women) at the Flight Analogs Unit, UTMB. Direct arterial and venous measurements were made with ultrasound to evaluate changes in vascular structure and function. Arterial function was assessed, in the arm and leg, during a reactive hyperemia protocol and during sublingual nitroglycerin administration to gauge the contributions of endothelial dependent and independent dilator function respectively. Venous function was assessed in dorsal hand and foot veins during the administration of pharmaceuticals to assess constrictor and dilator function. Both gender and day effects are seen in arterial dilator function to reactive hyperemia, but none are seen with nitroglycerin. There are also differences in the wall thickness in the arm vs the leg during bed rest, which return toward pre-bed rest levels by day 90. More subjects are required, especially females as there is not sufficient power to properly analyze venous function. Day 90 data are most underpowered.

A newly developed solution enhances thirty-hour preservation in a canine lung transplantation model.

PubMed

Liu, C J; Ueda, M; Kosaka, S; Hirata, T; Yokomise, H; Inui, K; Hitomi, S; Wada, H

1996-09-01

Ischemia and reperfusion cause the production of oxygen free radicals. These damage grafts or disrupt normal vascular homeostatic mechanisms, with a parallel reduction in endothelial nitric oxide and adenosine 3',5'-cyclic monophosphate levels. We hypothesized that lung preservation failure may be related to these events. To improve lung preservation, we prepared a new ET-Kyoto solution, which contains N-acetylcysteine (a radical scavenger), nitroglycerin (to elevate the nitric oxide level), and dibutyryl adenosine 3',5'-cyclic monophosphate (to elevate the adenosine 3',5'-cyclic monophosphate level) and examined its efficacy in a canine single-lung transplantation model. Lungs were flushed with new ET-Kyoto solution (group I, n = 9), basal ET-Kyoto solution (group II, n = 6), basal ET-Kyoto solution plus ethanol and propylene glycol (solvents of nitroglycerin; group III, n = 6), or low-potassium dextran glucose solution (group IV, n = 6), and stored at 4 degrees C for 30 hours. After left single-lung transplantation, the right main bronchus and right pulmonary artery were ligated and the functions of the transplanted lung were assessed for 6 hours. Arterial oxygen tension was significantly higher in group I than in groups II, III, and IV (p < 0.05). Peak inspiratory pressure and wet-to-dry lung weight ratio were significantly lower in group I than in groups II and IV (p < 0.01). Histologic and ultrastructural studies showed better preservation in group I than in groups II, III, and IV. We conclude that the new ET-Kyoto solution provides enhanced 30-hour lung preservation.

Safety of peripheral intravenous administration of vasoactive medication.

PubMed

Cardenas-Garcia, Jose; Schaub, Karen F; Belchikov, Yuly G; Narasimhan, Mangala; Koenig, Seth J; Mayo, Paul H

2015-09-01

Central venous access is commonly performed to administer vasoactive medication. The administration of vasoactive medication via peripheral intravenous access is a potential method of reducing the need for central venous access. The aim of this study was to evaluate the safety of vasoactive medication administered through peripheral intravenous access. Over a 20-month period starting in September 2012, we monitored the use of vasoactive medication via peripheral intravenous access in an 18-bed medical intensive care unit. Norepinephrine, dopamine, and phenylephrine were all approved for use through peripheral intravenous access. A total of 734 patients (age 72 ± 15 years, male/female 398/336, SAPS II score 75 ± 15) received vasoactive medication via peripheral intravenous access 783 times. Vasoactive medication used was norepinephrine (n = 506), dopamine (n = 101), and phenylephrine (n = 176). The duration of vasoactive medication via peripheral intravenous access was 49 ± 22 hours. Extravasation of the peripheral intravenous access during administration of vasoactive medication occurred in 19 patients (2%) without any tissue injury following treatment, with local phentolamine injection and application of local nitroglycerin paste. There were 95 patients (13%) receiving vasoactive medication through peripheral intravenous access who eventually required central intravenous access. Administration of norepinephrine, dopamine, or phenylephrine by peripheral intravenous access was feasible and safe in this single-center medical intensive care unit. Extravasation from the peripheral intravenous line was uncommon, and phentolamine with nitroglycerin paste were effective in preventing local ischemic injury. Clinicians should not regard the use of vasoactive medication is an automatic indication for central venous access. © 2015 Society of Hospital Medicine.

Quality of medication information available on retail pharmacy Web sites.

PubMed

Ghoshal, Malini; Walji, Muhammad F

2006-12-01

The Internet is becoming an important source for medication information. Although the quality of consumer medication information (CMI) in brick and mortar pharmacies has been reported to be suboptimal, little is known about the quality of CMI offered by pharmacy Web sites. To evaluate the quality, readability, and provision of Web functionality of 4 popular medications (atenolol, nitroglycerin, atorvastatin, and glyburide) available on the websites of 3 of the largest retail pharmacies: Walgreens, CVS Pharmacy, and Rite Aid. The quality of online medication information was evaluated by 2 reviewers using a preexisting evaluation instrument created by a national panel of experts. Readability level was assessed using the Gunning Fog Test. We also assessed the presence of 4 Web-specific functional criteria: (1) capability for font enlargement, (2) availability of a glossary of terms, (3) presence of an "Ask a pharmacist" feature, and (4) access to detailed medication information or full prescribing information. Overall, medication information was 77% adherent to the criteria evaluated. When broken down by drug, CMI was most adherent for atorvastatin (83%), followed by glyburide (77%), atenolol (76%), and nitroglycerin (75%). The average readability level was found to be 10th grade. No pharmacy Web site provided the ability for font enlargement, a glossary of terms, or access to detailed medication information; however, all pharmacy Web sites provided an "Ask a pharmacist" service. Although pharmacy Web sites were found to have an overall good content quality, the high readability level of text, areas of incomplete information, and limited use of desirable Web functionality suggest room for improvement.

The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat

PubMed Central

Nagy-Grócz, Gábor; Laborc, Klaudia F.; Veres, Gábor; Bajtai, Attila; Bohár, Zsuzsanna; Zádori, Dénes; Fejes-Szabó, Annamária; Spekker, Eleonóra; Vécsei, László; Párdutz, Árpád

2017-01-01

The primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its receptors. Kynurenic acid is an endogenous glutamate receptor antagonist produced by the kynurenine pathway (KP). Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) convert l-tryptophan to N-formyl-l-kynurenine, to be further transformed to l-kynurenine. Kynurenine aminotransferase-II (KAT-II), l-kynurenine hydrolase (KYNU), and l-kynurenine 3-monooxygenase (KMO) are key enzymes in the later steps of the KP. Nitroglycerin (NTG) administration serves as both human and animal model of migraine, causing the activation and sensitization in the trigeminal system. A previous study demonstrated a reduction of KAT-II expression following NTG administration in animals. The goal of current tests was to identify the potential modulatory effect of NTG on other metabolizing enzymes of the KP in the caudal trigeminal nucleus (TNC) of rats. Four hours following the intraperitoneal injection of NTG (10 mg/kg), the rats were perfused transcardially and the TNC was extracted for Western blotting. Western blot studies revealed that the expression of TDO2, IDO1, KYNU, and KMO decreased in the TNC. The results demonstrated that NTG is able to downregulate the KP, with a potential influence on the glutamatergic system as well, contributing to the development of trigeminal activation and sensitization in animals. PMID:28659861

The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat.

PubMed

Nagy-Grócz, Gábor; Laborc, Klaudia F; Veres, Gábor; Bajtai, Attila; Bohár, Zsuzsanna; Zádori, Dénes; Fejes-Szabó, Annamária; Spekker, Eleonóra; Vécsei, László; Párdutz, Árpád

2017-01-01

The primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its receptors. Kynurenic acid is an endogenous glutamate receptor antagonist produced by the kynurenine pathway (KP). Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) convert l-tryptophan to N -formyl-l-kynurenine, to be further transformed to l-kynurenine. Kynurenine aminotransferase-II (KAT-II), l-kynurenine hydrolase (KYNU), and l-kynurenine 3-monooxygenase (KMO) are key enzymes in the later steps of the KP. Nitroglycerin (NTG) administration serves as both human and animal model of migraine, causing the activation and sensitization in the trigeminal system. A previous study demonstrated a reduction of KAT-II expression following NTG administration in animals. The goal of current tests was to identify the potential modulatory effect of NTG on other metabolizing enzymes of the KP in the caudal trigeminal nucleus (TNC) of rats. Four hours following the intraperitoneal injection of NTG (10 mg/kg), the rats were perfused transcardially and the TNC was extracted for Western blotting. Western blot studies revealed that the expression of TDO2, IDO1, KYNU, and KMO decreased in the TNC. The results demonstrated that NTG is able to downregulate the KP, with a potential influence on the glutamatergic system as well, contributing to the development of trigeminal activation and sensitization in animals.

Photolysis of RDX and nitroglycerin in the context of military training ranges.

PubMed

Bordeleau, Geneviève; Martel, Richard; Ampleman, Guy; Thiboutot, Sonia

2013-09-01

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and nitroglycerin (NG) are two energetic materials commonly found in the environment on military training ranges. They are deposited on the ground in the form of solid particles, which can then dissolve in infiltration water or in surface water bodies. The objective of this study was to evaluate whether photolysis by sunlight can significantly contribute to the natural attenuation of RDX and NG (as solid particles or dissolved in surface water) at mid-northern latitudes, where training ranges of Canada and many European countries are located. Experiments conducted at 46.9°N show that both compounds are degraded by sunlight when dissolved in water, with half-lives between 1 and 120d, depending on the compound and time of year. Numerical models may be useful in predicting such photolysis rates, but the models should take into account current ozone levels, as older radiation datasets, collected before the ozone depletion observed since the late 1970s, underestimate the RDX/NG photolysis rate. For solid RDX or NG-bearing particles, photolysis is slower (half-lives of 2-4months), but the degradation rate is still rapid enough to make this process significant in a natural attenuation context. However, photolysis of NG embedded within solid propellant particles cannot proceed to completion, due to the stable nitrocellulose matrix of the propellant. Nonetheless, photolysis clearly constitutes an important attenuation mechanism that should be considered in conceptual models and included in numerical modeling efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of 4 classes of cardiovascular drugs on ventricular function in dogs with mitral regurgitation.

PubMed

Nakayama, Tomohiro; Nishijima, Yoshinori; Miyamoto, Mutsumi; Hamlin, Robert L

2007-01-01

There have been few trials in which dogs with mitral regurgitation (MR) have been treated with various cardioactive drugs to determine effects on left ventricular (LV) function. Four classes of cardiovascular drugs may improve LV function in dogs with MR without increasing MR. Nine mature dogs were included in the study. MR was produced in 9 dogs. Five months later under butorphanol narcosis, parameters of LV function and left atrial dimension (LAD) were monitored by LV micromanometry and echocardiography/Doppler. Dogs were given (in random order) enalaprilat, nitroglycerine, ouabain, milrinone, and placebo. Nitroglycerin produced no significant change; milrinone and ouabain increased contractility; ouabain decreased heart rate; and there was evidence that enalaprilat and milrinone decreased LAD. Milrinone and ouabain decreased isovolumetric contraction time and therefore the time available for MR. There was no evidence that a positive inotrope increased MR despite increasing LV contractility and stroke volume. This study contradicts the hypotheses that (1) strengthening the left ventricle may increase MR and (2) treatment of MR (even before symptoms of heart failure develop) may decrease LAD. It is reasonable that strengthening the force of LV contraction should increase the driving pressure for MR; however, this effect did not appear to increase MR. Although some investigators believe that treating dogs with MR with afterload reducers and decreasing hindrance to ejection of blood from the LV to aorta may lengthen life by decreasing MR, there did not appear to be a reduction in MR, at least in response to the angiotensin-converting enzyme (ACE) inhibitor.

N-acetylcysteine improves coronary and peripheral vascular function.

PubMed

Andrews, N P; Prasad, A; Quyyumi, A A

2001-01-01

We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. Coronary atherosclerosis is associated with endothelial dysfunction and reduced NO activity. In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAC. In 14 patients femoral vascular responses to ACH, NTG and SNP were measured before and after NAC. Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated ACH-mediated coronary vasodilation; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diameter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05). Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis.

Storage of nitroglycerin (NTG) admixed with HBOC-201 for 30 days in polyolefin plastic bags: a pilot study.

PubMed

Nigam, Savita; McCarron, Richard; Arnaud, Francoise

2017-10-01

Hemorrhaged animals have benefited from resuscitation with the hemoglobin-based oxygen carrier (HBOC-201). Co-infusion of nitric oxide (NO) via separate intravascular lines is effective in attenuating HBOC-induced elevation of blood pressure. We tested whether nitroglycerin (NTG) and HBOC-201 can be packaged together as a single drug for resuscitation. Since NTG binds easily to plastics such as polyvinylchloride, we assessed the stability of this combination in oxygen barrier double-layer ethylene-vinyl alcohol/polyolefin bags over a 30-day period. Outcome measures indicative of the stability of HBOC/NTG were reported as changes in levels of hemoglobin (Hb), methemoglobin (MetHb), NTG, and nitrite over time. Individual tightly sealed small aliquots of HBOC/NTG were prepared under nitrogen and analyzed in a timely fashion from 0 to 30 days using hematology instruments, HPLC, FPLC, and chemiluminescence. The level of NTG in the HBOC/NTG mixture was reduced significantly over time whereas it was stable in control mixtures of NTG/saline. The level of total Hb in the HBOC/NTG and HBOC/saline mixtures remained stable over time. MetHb formed and increased to 6% up to day 1 and then slowly decreased in the HBOC/NTG mixture whereas it remained unchanged in the HBOC/saline mixture. Nitrite was produced in the HBOC/NTG group upon mixing, was increased at day 1, and then became undetectable. The reaction between HBOC-201 and NTG occurring upon mixing and developing over time in polyolefin bags makes the long-term storage of this mixed combination inappropriate.

Forward and Backward Pressure Waveform Morphology in Hypertension

PubMed Central

Li, Ye; Gu, Haotian; Fok, Henry; Alastruey, Jordi

2017-01-01

We tested the hypothesis that increased pulse wave reflection and altered backward waveform morphology contribute to increased pulse pressure in subjects with higher pulse pressure compared with lower pulse pressure and to actions of vasoactive drugs to increase pulse pressure. We examined the relationship of backward to forward wave morphology in 158 subjects who were evaluated for hypertension (including some normotensive subjects) divided into 3 groups by central pulse pressure: group 1, 33±6.5 mm Hg; group 2, 45±4.1 mm Hg; and group 3, 64±12.9 mm Hg (means±SD) and in healthy normotensive subjects during administration of inotropic and vasomotor drugs. Aortic pressure and flow in the aortic root were estimated by carotid tonometry and Doppler sonography, respectively. Morphology of the backward wave relative to the forward wave was similar in subjects in the lowest and highest tertiles of pulse pressure. Similar results were seen with the inotropic, vasopressor and vasodilator drugs, dobutamine, norepinephrine, and phentolamine, with the backward wave maintaining a constant ratio to the forward wave. However, nitroglycerin, a drug with a specific action to dilate muscular conduit arteries, reduced the amplitude of the backward wave relative to the forward wave from 0.26±0.018 at baseline to 0.19±0.019 during nitroglycerin 30 μg/min IV (P<0.01). These results are best explained by an approximately constant amount of reflection of the forward wave from the peripheral vasculature. The amount of reflection can be modified by dilation of peripheral muscular conduit arteries but contributes little to increased pulse pressure in hypertension. PMID:27920128

A retrospective review of safety using a nursing driven protocol for autonomic dysreflexia in patients with spinal cord injuries.

PubMed

Solinsky, Ryan; Svircev, Jelena N; James, Jennifer J; Burns, Stephen P; Bunnell, Aaron E

2016-11-01

Autonomic dysreflexia is a potentially life-threatening condition which afflicts a significant proportion of individuals with spinal cord injuries (SCI). To date, the safety and efficacy of several commonly used interventions for this condition have not been studied. A retrospective chart review of the safety of a previously implemented nursing driven inpatient autonomic dysreflexia protocol. Seventy-eight male patients with SCI who experienced autonomic dysreflexia while inpatient at our Veterans Affairs SCI unit over a 3-1/2-year period were included. The safety of a nursing driven protocol utilizing conservative measures, nitroglycerin paste, and oral hydralazine was evaluated. Occurrence of adverse events and relative hypotensive events during all episodes treated with the protocol, and efficacy of attaining target blood pressure for all episodes with protocol adherence and for initial episode experienced by each patient. Four hundred forty-five episodes of autonomic dysreflexia were recorded in the study period, with 92% adherence to the protocol. When the protocol was followed, target blood pressure was achieved for 97.6% of all episodes. Twenty-three total adverse events occurred (5.2% of all episodes). All adverse events were due to hypotension and only 0.9% required interventions beyond clinical monitoring. Of each patient's initial autonomic dysreflexia episode, 97.3% resolved using the protocol without need for further escalation of care. This inpatient nursing driven-protocol for treating autonomic dysreflexia utilizing conservative measures, nitroglycerin paste and oral hydralazine achieved target blood pressure with a high success rate and a low incidence of adverse events.

Bioactivation of organic nitrates and the mechanism of nitrate tolerance.

PubMed

Klemenska, Emila; Beresewicz, Andrzej

2009-01-01

Organic nitrates, such as nitroglycerin, are commonly used in the therapy of cardiovascular disease. Long-term therapy with these drugs, however, results in the rapid development of nitrate tolerance, limiting their hemodynamic and anti-ischemic efficacy. In addition, nitrate tolerance is associated with the expression of potentially deleterious modifications such as increased oxidative stress, endothelial dysfunction, and sympathetic activation. In this review we discuss current concepts regarding the mechanisms of organic nitrate bioactivation, nitrate tolerance, and nitrate-mediated oxidative stress and endothelial dysfunction. We also examine how hydralazine may prevent nitrate tolerance and related endothelial dysfunction.

ALERT: Revatio is another brand name for sildenafil.

PubMed

Koczmara, Christine; Hyland, Sylvia; Greenall, Julie

2009-01-01

In this column, the authors highlight a medication incident that occurred with Revatio (sildenafil), along with the learnings and recommendations from a previously published ISMP Canada Safety Bulletin. It is well-known to health care practitioners that use of nitroglycerin therapy is contraindicated in patients taking sildenafil (commonly known as Viagra). Many health care practitioners may be unaware that sildenafil is also marketed under the brand name Revatio for treatment of primary pulmonary hypertension or pulmonary hypertension secondary to connective tissue disease. The following incident signals the need to heighten the awareness that Revatio is a brand name for sildenafil.

Low vulnerability explosives (LOVEX) for mass-use warheads

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pruneda, C.; Jessop, E.; McGuire, R.

1990-03-13

There is an ongoing effort at Lawrence Livermore National Laboratory to develop explosives with a significantly lower vulnerability to battlefield environments (bullets, fragments, sympathetic detonation) than current explosives (TNT and Comp B) without sacrificing performance or increasing costs. The approach taken is to develop a composite explosive which is comprised of inexpensive fillers such as RDX, NaNO{sub 3}, Al and a low modulus binder system. The binder system uses nitroglycerin/triacetin as an energetic plasticizer. This paper discusses the experimental results to date in vulnerability, performance and processing. 7 refs., 8 figs., 6 tabs.

Protein kinase G regulates the basal tension and plays a major role in nitrovasodilator-induced relaxation of porcine coronary veins.

PubMed

Qi, H; Zheng, X; Qin, X; Dou, D; Xu, H; Raj, J U; Gao, Y

2007-12-01

Coronary venous activity is modulated by endogenous and exogenous nitrovasodilators. The present study was to determine the role of protein kinase G (PKG) in the regulation of the basal tension and nitrovasodilator-induced relaxation of coronary veins. Effects of a PKG inhibitor on the basal tension and responses induced by nitroglycerin, DETA NONOate, and 8-Br-cGMP in isolated porcine coronary veins were determined. Cyclic cGMP was measured with radioimmunoassay. PKG activity was determined by measuring the incorporation of 32P from gamma-32P-ATP into the specific substrate BPDEtide. Rp-8-Br-PET-cGMPS, a specific PKG inhibitor, increased the basal tension of porcine coronary veins and decreased PKG activity. The increase in tension was 38% of that caused by nitro-L-arginine. Relaxation of the veins induced by nitroglycerin and DETA NONOate was accompanied with increases in cGMP content and PKG activity. These effects were largely eliminated by inhibiting soluble guanylyl cyclase with ODQ. The increase in PKG activity induced by the nitrovasodilators was abolished by Rp-8-Br-PET-cGMPS. The relaxation caused by these dilators and by 8-Br-cGMP at their EC50 was attenuated by the PKG inhibitor by 51-66%. These results suggest that PKG is critically involved in nitric oxide-mediated regulation of the basal tension in porcine coronary veins and that it plays a primary role in relaxation induced by nitrovasodilators. Since nitric oxide plays a key role in modulating coronary venous activity, augmentation of PKG may be a therapeutic target for improving coronary blood flow.

Antianginal Efficacy of Ivabradine/Metoprolol Combination in Patients With Stable Angina.

PubMed

Zarifis, John; Kallistratos, Manolis; Katsivas, Apostolos

2016-12-01

Medical treatment is the main clinical strategy for controlling patients with chronic stable angina and improving their quality of life (QoL). Ivabradine treatment on top of metoprolol decreases angina symptoms and improves QoL in patients with stable angina and coronary artery disease (CAD). This is a post hoc analysis (636 CAD patients given ivabradine/metoprolol free combination) of a prospective, noninterventional study that included 2403 patients with CAD and stable angina. Data were recorded at baseline at 1 and 4 months after inclusion. Patient QoL was assessed using the EQ-5D questionnaire. From baseline to study completion; ivabradine administration on top of metoprolol decreased heart rate (HR) from 80.8 ± 9.6 to 64.2 ± 6.2 bpm (P < 0.001). Mean number of angina attacks decreased from 2.0 ± 2.0/wk to 0.2 ± 0.6/wk (P < 0.001), whereas nitroglycerin consumption decreased from 1.4 ± 1.9 times/wk to 0.1 ± 0.4 times/wk (P < 0.001). The percentage of patients in Canadian Cardiovascular Society angina class III to IV decreased from 15.4% to 1.9% (P < 0.001). The improvement of symptoms and angina class led to a significant 14.7-point increase in EQ-5D questionnaire score (P < 0.001). Patients with increased HR showed greater improvement (P = 0.001). Adherence to treatment during the entire trial was high (98%). Ivabradine combined with metoprolol significantly decreased angina symptoms and use of nitroglycerin in patients with stable angina and CAD, leading to improved QoL. The benefits observed with this combination explain the high rate of adherence to treatment. © 2016 Wiley Periodicals, Inc.

Pharmacologic intervention for retained placenta: a systematic review and meta-analysis.

PubMed

Duffy, James M N; Mylan, Sophie; Showell, Marian; Wilson, Matthew J A; Khan, Khalid S

2015-03-01

To assess the effectiveness and safety of pharmacologic interventions for the treatment of retained placenta (when the placenta remains undelivered after 30 minutes of active management of the third stage of labor). We searched: 1) Cochrane Central Register of Controlled Trials (CENTRAL), 2) Cochrane Pregnancy and Childbirth Group's Trials Register, 3) EMBASE, and 4) MEDLINE from inception to June 2014. Randomized controlled trials comparing a pharmacologic intervention(s) with a placebo for the treatment of retained placenta were included. Sixteen randomized controlled trials, including 1,683 participants, were included. Study characteristics and quality were recorded. The meta-analysis was based on random-effects methods for pooled data. There were no statistically significant differences in the requirement to perform manual removal of a placenta in patients treated with oxytocin (55% compared with 60%; relative risk [RR] 0.86, 95% confidence interval [CI] 0.73-1.02; 10 randomized controlled trials [RCTs]), prostaglandins (44% compared with 55%; RR 0.82, 95% CI 0.58-1.15; four RCTs), nitroglycerin (85% compared with 80%; RR 1.06, 95% CI 0.80-1.41; one RCT), or oxytocin and nitroglycerin (52% compared with 79%; RR 0.23, 95% CI 0.01-8.48; two RCTs) compared with placebo. There was limited reporting of secondary outcomes. As opposed to the use of oxytocin as part of the active management of the third stage of labor that has been shown to diminish bleeding in the third stage, once the diagnosis of retained placenta has been made, no pharmacologic treatment has been shown to be effective. When retained placenta is diagnosed, immediate manual removal of the placenta should be considered. PROSPERO International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42014010641.

Effects of topical nipradilol, a β blocking agent with α blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans

PubMed Central

Kanno, M.; Araie, M.; Koibuchi, H.; Masuda, K.

2000-01-01

AIMS—To study the effects of topical nipradilol, a non-selective β blocker with α blocking and nitroglycerin-like activities, on intraocular pressure (IOP) and aqueous humour dynamics in normal humans and in patients with ocular hypertension.
METHODS—Nipradilol (0.06%, 0.125%, 0.25%, 0.5%) was applied to normal volunteers (n = 12) to test for IOP lowering effects. In a second group of normal volunteers (n = 11), nipradilol (0.125% and 0.25%) and timolol (0.5%) were compared for IOP lowering effects. After a single administration of 0.25% nipradilol, IOP, flare intensity in the anterior chamber, aqueous flow, uveoscleral outflow, tonographic outflow facility, and episcleral venous pressure were either directly measured or mathematically calculated. Topical nipradilol (0.25%) was administered to 24 patients with ocular hypertension twice daily for 8 weeks.
RESULTS—Administration of 0.25% nipradilol decreased IOP with a maximum reduction of 4.2 mm Hg lasting 12 hours. A single instillation of both 0.25% nipradilol and 0.5% timolol reduced the IOP in normotensive human subjects to the same degree. A single instillation of 0.25% nipradilol decreased the aqueous flow rate in the treated eye by 20%. Nipradilol produced no significant effect in tonographic outflow facility or episcleral venous pressure, but uveoscleral outflow was increased. In patients with ocular hypertension, twice daily instillation of 0.25% nipradilol decreased IOP without tachyphylaxis for the 8 week test period.
CONCLUSION—Topical nipradilol (0.25%) reduced IOP by decreasing the aqueous flow rate and probably also by increasing uveoscleral outflow. Nipradilol should be further investigated as a new antiglaucoma drug.

 PMID:10684841

Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices.

PubMed

Trapani, A; Gonçalves, L F; Trapani, T F; Franco, M J; Galluzzo, R N; Pires, M M S

2016-07-01

To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR). This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples. There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia. The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin.

PubMed

Opelt, Marissa; Eroglu, Emrah; Waldeck-Weiermair, Markus; Russwurm, Michael; Koesling, Doris; Malli, Roland; Graier, Wolfgang F; Fassett, John T; Schrammel, Astrid; Mayer, Bernd

2016-11-11

Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN), resulting in activation of soluble guanylate cyclase (sGC) and cGMP-mediated vasodilation. We have previously shown that a minor reaction of ALDH2-catalyzed GTN bioconversion, accounting for about 5% of the main clearance-based turnover yielding inorganic nitrite, results in direct NO formation and concluded that this minor pathway could provide the link between vascular GTN metabolism and activation of sGC. However, lack of detectable NO at therapeutically relevant GTN concentrations (≤1 μm) in vascular tissue called into question the biological significance of NO formation by purified ALDH2. We addressed this issue and used a novel, highly sensitive genetically encoded fluorescent NO probe (geNOp) to visualize intracellular NO formation at low GTN concentrations (≤1 μm) in cultured vascular smooth muscle cells (VSMC) expressing an ALDH2 mutant that reduces GTN to NO but lacks clearance-based GTN denitration activity. NO formation was compared with GTN-induced activation of sGC. The addition of 1 μm GTN to VSMC expressing either wild-type or C301S/C303S ALDH2 resulted in pronounced intracellular NO elevation, with maximal concentrations of 7 and 17 nm, respectively. Formation of GTN-derived NO correlated well with activation of purified sGC in VSMC lysates and cGMP accumulation in intact porcine aortic endothelial cells infected with wild-type or mutant ALDH2. Formation of NO and cGMP accumulation were inhibited by ALDH inhibitors chloral hydrate and daidzin. The present study demonstrates that ALDH2-catalyzed NO formation is necessary and sufficient for GTN bioactivation in VSMC. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat.

PubMed

Ferrari, L F; Levine, J D; Green, P G

2016-03-11

Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN's very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ∼ 30 min in male and ∼ 45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed-onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggests potential novel risk factors and targets for the treatment of migraine. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Involvement of BDNF/TrkB and ERK/CREB axes in nitroglycerin-induced rat migraine and effects of estrogen on these signals in the migraine

PubMed Central

Guo, Jiu-Qing; Deng, Hui-Hui; Bo, Xiao

2017-01-01

ABSTRACT Migraine is a highly prevalent headache disorder, especially in women. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinases (TrkB), as well as extracellular signal-regulated kinase (ERK) and its downstream target c-AMP-responsive element binding protein (CREB) are strongly associated with the transmission of nociceptive information. However, the involvement of these substances in migraine has rarely been examined. In the present study, intraperitoneal injection of nitroglycerin (NTC) successfully induced rat migraine attack, as evidenced by behavioral testing. The location and abundance of these substances in the migraine model were determined by immunohistochemistry, real-time polymerase chain reaction (RT-PCR), western blot and enzyme-linked immunosorbant assays (ELISA). Results showed that BDNF, TrkB, phosphor(p)-ERK and p-CREB were up-regulated in the brain neurons of both male and female rats with NTG-induced migraine compared to non-migraine control, whereas their expression levels were decreased in headache-free intervals of the migraine compared to migraine attacks. Estrogen is an important contributor to migraine. Female ovariectomized rats showed significant reduction in the expression of BDNF, TrkB, p-CREB and p-ERK in both attacks and intervals of NTG-induced migraine, relative to rats that have their ovaries. But, intraperitoneal administration of exogenous estrogen recovered their expression in ovariectomized rats. Collectively, this study unveiled a positive correlation of BDNF/TrkB and ERK/CREB axes in NTG-induced migraine and promoting effects of estrogen on their signals in the migraine. These findings contribute to further understanding the pathogenesis of migraine in the molecular basis. PMID:27875242

Impact of perioperative blood pressure variability on health resource utilization after cardiac surgery: an analysis of the ECLIPSE trials.

PubMed

Aronson, Solomon; Levy, Jerrold H; Lumb, Philip D; Fontes, Manuel; Wang, Yamei; Crothers, Tracy A; Sulham, Katherine A; Navetta, Marco S

2014-06-01

To examine the impact of blood pressure control on hospital health resource utilization using data from the ECLIPSE trials. Post-hoc analysis of data from 3 prospective, open-label, randomized clinical trials (ECLIPSE trials). Sixty-one medical centers in the United States. Patients 18 years or older undergoing cardiac surgery. Clevidipine was compared with nitroglycerin, sodium nitroprusside, and nicardipine. The ECLIPSE trials included 3 individual randomized open-label studies comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine. Blood pressure control was assessed as the integral of the cumulative area under the curve (AUC) outside specified systolic blood pressure ranges, such that lower AUC represents less variability. This analysis examined surgery duration, time to extubation, as well as intensive care unit (ICU) and hospital length of stay (LOS) in patients with AUC≤10 mmHg×min/h compared to patients with AUC>10 mmHg×min/h. One thousand four hundred ten patients were included for analysis; 736 patients (52%) had an AUC≤10 mmHg×min/h, and 674 (48%) had an AUC>10 mmHg×min/h. The duration of surgery and ICU LOS were similar between groups. Time to extubation and postoperative LOS were both significantly shorter (p = 0.05 and p<0.0001, respectively) in patients with AUC≤10. Multivariate analysis demonstrates AUC≤10 was significantly and independently associated with decreased time to extubation (hazard ratio 1.132, p = 0.0261) and postoperative LOS (hazard ratio 1.221, p = 0.0006). Based on data derived from the ECLIPSE studies, increased perioperative BP variability is associated with delayed time to extubation and increased postoperative LOS. Copyright © 2014 Elsevier Inc. All rights reserved.

Nitroglycerin-induced changes in facial skin temperature: 'cold nose' as a predictor of headache?

PubMed

Zaproudina, Nina; Närhi, Matti; Lipponen, Jukka A; Tarvainen, Mika P; Karjalainen, Pasi A; Karhu, Jari; Airaksinen, Olavi; Giniatullin, Rashid

2013-11-01

Nitroglycerin (NTG) often induces headaches when used to treat cardiac diseases. Such property of NTG has been widely used in modelling of migraine-like headaches. However, background reasons, predisposing to the development of NTG-headache, are less studied. The main aim of our study was to find, using NTG model, easily accessible markers of the vascular changes associated with headache. Because changes in the blood flow alter the local skin temperature (Tsk), we studied the relationship between the regional changes in the facial Tsk and NTG-induced headaches. Tsk was measured with infrared thermography in 11 healthy women during 3 h after sublingual NTG administration. NTG caused headache in five women, and four of them were the first-degree relatives of migraine patients. Notably, before NTG administration, subjects in the headache group had lower Tsk values, especially in the nose area, than women in the pain-free group (n = 6). NTG-induced headache was associated with a long-lasting increase of Tsk over the baseline. In sharp contrast, in the pain-free group, the Tsk reduced and returned rapidly to the baseline. Thus, the low baseline level and greater increase of regional Tsk correlated with the incidence of headache that supports a role of greater vascular changes in headache happening on the basis of the dissimilarities in vascular tone. An easily accessible phenomenon of 'cold nose' may indicate background vascular dysfunctions in individuals with predisposition to headache. Facial infrared thermography, coupled with NTG administration, suggests a novel temporally controlled approach for non-invasive investigation of vascular processes accompanying headaches. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Efficacy of nitroglycerine ointment in the treatment of pediatric anal fissure.

PubMed

Joda, Ali E; Al-Mayoof, Ali F

2017-11-01

Anal fissure is the most common anal disease in children. In the past few decades, the understanding of its pathophysiology has led to a progressive reduction in invasive procedures in favor of conservative treatment based on stool softeners and the relaxation of the anal sphincter. This randomized controlled study assessed the safety and efficacy of nitroglycerine (NTG) ointment in the treatment of pediatric anal fissure, which had not yet been proved. An unequal randomized controlled study included 105 pediatric patients with anal fissure who had presented to the private and outpatient clinics of the Central Teaching Hospital of Pediatrics during the period from February 2015 to May 2016. The control group consisted of 70 patients. Both groups were treated with classical conservative therapy of sitz bath, stool softener, and local anesthetic. In the second group, chemical sphincterotomy with 0.2% NTG ointment was used in 35 patients, and was applied at the anal canal twice daily for 8weeks. The primary outcomes of symptomatic improvement and healed fissure, as well as side effects, were analyzed. The average age of patients was 2years (range, 4months to 5years). Patients in the NTG group had 77% symptomatic relief and 60% healed fissure compared to the control group, which had 54% and 32.8% respectively. All were statistically significant. No serious adverse effects were noticed during the treatment period. The use of 0.2% NTG ointment is an effective therapy for anal fissure in children in terms of good healing rate and rapid symptom relief, but it has the drawback of a long treatment period, making patient compliance more difficult, in addition to the problems of tolerance and recurrence. Prospective randomized controlled study (treatment study). Type 2. Copyright © 2017 Elsevier Inc. All rights reserved.

Ratio of serum levels of AGEs to soluble form of RAGE is a predictor of endothelial function.

PubMed

Kajikawa, Masato; Nakashima, Ayumu; Fujimura, Noritaka; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Matsumoto, Takeshi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Noma, Kensuke; Takeuchi, Masayoshi; Matsui, Takanori; Yamagishi, Sho-Ichi; Higashi, Yukihito

2015-01-01

Advanced glycation end products (AGEs) and their specific receptor, the receptor for AGEs (RAGE), play an important role in atherosclerosis. Recently, a soluble form of RAGE (sRAGE) has been identified in human serum. However, the role of sRAGE in cardiovascular disease is still controversial. There is no information on the association between simultaneous measurements of AGEs and sRAGE and vascular function. In this study, we evaluated the associations between serum levels of AGEs and sRAGE, ratio of AGEs to sRAGE, and vascular function. We measured serum levels of AGEs and sRAGE and assessed vascular function by measurement of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in 110 subjects who underwent health examinations. Multivariate regression analyses were performed to identify factors associated with vascular function. Univariate regression analysis revealed that FMD correlated with age, BMI, systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, HDL cholesterol, glucose, smoking pack-years, nitroglycerine-induced vasodilation, serum levels of AGEs and sRAGE, and ratio of AGEs to sRAGE. Multivariate analysis revealed that the ratio of AGEs to sRAGE remained an independent predictor of FMD, while serum level of AGEs alone or sRAGE alone was not associated with FMD. These findings suggest that sRAGE may have a counterregulatory mechanism that is activated to counteract the vasotoxic effect of the AGE-RAGE axis. The ratio of AGEs to sRAGE may be a new chemical biomarker of endothelial function. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Meta-analysis of acupuncture therapy for the treatment of stable angina pectoris.

PubMed

Zhang, Ze; Chen, Min; Zhang, Li; Zhang, Zhe; Wu, Wensheng; Liu, Jun; Yan, Jun; Yang, Guanlin

2015-01-01

Angina pectoris is a common symptom imperiling patients' life quality. The aim of this study is to evaluate the efficacy and safety of acupuncture for stable angina pectoris. Clinical randomized-controlled trials (RCTs) comparing the efficacy of acupuncture to conventional drugs in patients with stable angina pectoris were searched using the following database of PubMed, Medline, Wanfang and CNKI. Overall odds ratio (ORs) and weighted mean difference (MD) with their 95% confidence intervals (CI) were calculated by using fixed- or random-effect models depending on the heterogeneity of the included trials. Total 8 RCTs, including 640 angina pectoris cases with 372 patients received acupuncture therapy and 268 patients received conventional drugs, were included. Overall, our result showed that acupuncture significantly increased the clinical curative effects in the relief of angina symptoms (OR=2.89, 95% CI=1.87-4.47, P<0.00001) and improved the electrocardiography (OR=1.83, 95% CI=1.23-2.71, P=0.003), indicating that acupuncture therapy was superior to conventional drugs. Although there was no significant difference in overall effective rate relating reduction of nitroglycerin between two groups (OR=2.13, 95% CI=0.90-5.07, P=0.09), a significant reduction on nitroglycerin consumption in acupuncture group was found (MD=-0.44, 95% CI=-0.64, -0.24, P<0.0001). Furthermore, the time to onset of angina relief was longer for acupuncture therapy than for traditional medicines (MD=2.44, 95% CI=1.64-3.24, P<0.00001, min). No adverse effects associated with acupuncture therapy were found. Acupuncture may be an effective therapy for stable angina pectoris. More clinical trials are needed to systematically assess the role of acupuncture in angina pectoris.

Meta-analysis of acupuncture therapy for the treatment of stable angina pectoris

PubMed Central

Zhang, Ze; Chen, Min; Zhang, Li; Zhang, Zhe; Wu, Wensheng; Liu, Jun; Yan, Jun; Yang, Guanlin

2015-01-01

Angina pectoris is a common symptom imperiling patients’ life quality. The aim of this study is to evaluate the efficacy and safety of acupuncture for stable angina pectoris. Clinical randomized-controlled trials (RCTs) comparing the efficacy of acupuncture to conventional drugs in patients with stable angina pectoris were searched using the following database of PubMed, Medline, Wanfang and CNKI. Overall odds ratio (ORs) and weighted mean difference (MD) with their 95% confidence intervals (CI) were calculated by using fixed- or random-effect models depending on the heterogeneity of the included trials. Total 8 RCTs, including 640 angina pectoris cases with 372 patients received acupuncture therapy and 268 patients received conventional drugs, were included. Overall, our result showed that acupuncture significantly increased the clinical curative effects in the relief of angina symptoms (OR=2.89, 95% CI=1.87-4.47, P<0.00001) and improved the electrocardiography (OR=1.83, 95% CI=1.23-2.71, P=0.003), indicating that acupuncture therapy was superior to conventional drugs. Although there was no significant difference in overall effective rate relating reduction of nitroglycerin between two groups (OR=2.13, 95% CI=0.90-5.07, P=0.09), a significant reduction on nitroglycerin consumption in acupuncture group was found (MD=-0.44, 95% CI=-0.64, -0.24, P<0.0001). Furthermore, the time to onset of angina relief was longer for acupuncture therapy than for traditional medicines (MD=2.44, 95% CI=1.64-3.24, P<0.00001, min). No adverse effects associated with acupuncture therapy were found. Acupuncture may be an effective therapy for stable angina pectoris. More clinical trials are needed to systematically assess the role of acupuncture in angina pectoris. PMID:26131084

Relationship of visit-to-visit and ambulatory blood pressure variability to vascular function in African Americans.

PubMed

Diaz, Keith M; Veerabhadrappa, Praveen; Kashem, Mohammed A; Feairheller, Deborah L; Sturgeon, Kathleen M; Williamson, Sheara T; Crabbe, Deborah L; Brown, Michael D

2012-01-01

Visit-to-visit clinic blood pressure variability (BPV) and 24-h BPV have both been identified as independent risk factors for cardiovascular (CV) morbidity and mortality; however, the mechanisms contributing to the increased CV risk as yet are unclear. The purpose of this study was to assess the relationship between BPV and endothelial function in a cohort of putatively healthy African Americans. A total of 36 African Americans who were sedentary, non-diabetic, non-smoking, free of CV and renal disease and not on antihypertensive medication followed an American Heart Association low fat, low salt diet for 6 weeks. Upon completion of the 6-week dietary stabilization period, participants underwent 24-h ambulatory BP monitoring and had their office blood pressure (BP) measured on 3 separate days. Right brachial artery diameter was assessed at rest, during reactive hyperemia (flow-mediated vasodilation: FMD), and after nitroglycerin administration (nitroglycerin-mediated vasodilation: NMD). Participants classified as having decreased endothelial function according to either %FMD or the FMD/NMD ratio had significantly higher 24-h BPV and a trend for higher visit-to-visit BPV when compared with participants with normal endothelial function. Continuous variable analyses revealed a significant positive association between NMD and 24-h diastolic BPV (DBPV). Visit-to-visit systolic BPV (SBPV), 24-h SBPV and 24-h DBPV were all negatively associated with the FMD/NMD ratio. All relationships remained significant after adjustment for age, body mass index and mean BP levels. These results may suggest that BPV is increased in African Americans with decreased endothelial function and is associated with the vascular smooth muscle response to nitric oxide.

Protein kinase G regulates the basal tension and plays a major role in nitrovasodilator-induced relaxation of porcine coronary veins

PubMed Central

Qi, H; Zheng, X; Qin, X; Dou, D; Xu, H; Raj, J U; Gao, Y

2007-01-01

Background and purpose: Coronary venous activity is modulated by endogenous and exogenous nitrovasodilators. The present study was to determine the role of protein kinase G (PKG) in the regulation of the basal tension and nitrovasodilator-induced relaxation of coronary veins. Experimental approach: Effects of a PKG inhibitor on the basal tension and responses induced by nitroglycerin, DETA NONOate, and 8-Br-cGMP in isolated porcine coronary veins were determined. Cyclic cGMP was measured with radioimmunoassay. PKG activity was determined by measuring the incorporation of 32P from γ-32P-ATP into the specific substrate BPDEtide. Key results: Rp-8-Br-PET-cGMPS, a specific PKG inhibitor, increased the basal tension of porcine coronary veins and decreased PKG activity. The increase in tension was 38% of that caused by nitro-L-arginine. Relaxation of the veins induced by nitroglycerin and DETA NONOate was accompanied with increases in cGMP content and PKG activity. These effects were largely eliminated by inhibiting soluble guanylyl cyclase with ODQ. The increase in PKG activity induced by the nitrovasodilators was abolished by Rp-8-Br-PET-cGMPS. The relaxation caused by these dilators and by 8-Br-cGMP at their EC50 was attenuated by the PKG inhibitor by 51–66%. Conclusions and implications: These results suggest that PKG is critically involved in nitric oxide-mediated regulation of the basal tension in porcine coronary veins and that it plays a primary role in relaxation induced by nitrovasodilators. Since nitric oxide plays a key role in modulating coronary venous activity, augmentation of PKG may be a therapeutic target for improving coronary blood flow. PMID:17891157

Cardiovascular Adaptations to Long Duration Head Down Tilt Bed Rest

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Meck, Janice V.; Martin, David S.; Freeman-Perez, Sondra A.; Riberio, Christine; Garcia, Kathleen M.; Waters, Wendy W.

2007-01-01

Orthostatic hypotension is a recognized risk for crewmembers returning from space. Numerous cardiovascular mechanisms have been proposed to account for this problem including vascular and cardiac dysfunction. We studied arterial and cardiac function in 6-degree head-down tilt bed rest, which is the most widely accepted ground-based analog of spaceflight. Eleven subjects are included in this study (8 men and 3 women). Data analysis was limited to the first 49 days, and compared to pre-bed rest baseline data. Using ultrasound, data was collected on arterial diameters and flows at baseline and during reactive hyperemia and following administration of nitroglycerin. Echocardiography was used to acquire information regarding systolic and diastolic function as well as ventricular mass and diameter. Plasma volumes were significantly decreased by 7 days of bed rest and stayed down through 49 days. There were no differences in reactive hyperemic response in the arm at any time point. However, the hyperemic response in the leg was significantly increased at day 49. Arterial responses to nitroglycerin did not change over the duration of bed rest (day effect) in either the arm or leg, but there was a significant difference between the arm and the leg responses. There was a marked decrease in anterior tibial intimal-medial thickness at days 21, 35 and 49. Several cardiac functional parameters including IVRT, Mitral e-wave, ejection time, velocity of circumferential shortening and myocardial performance index were significantly changed following 49 days of bed rest. These data show that some cardiovascular measures change during bed rest, while others do not. Further study is needed to determine if these measures can provide any insight into the effects of bed rest, or spaceflight, on human cardiovascular performance.

Interrelationships Among Flow-Mediated Vasodilation, Nitroglycerine-Induced Vasodilation, Baseline Brachial Artery Diameter, Hyperemic Shear Stress, and Cardiovascular Risk Factors.

PubMed

Maruhashi, Tatsuya; Iwamoto, Yumiko; Kajikawa, Masato; Oda, Nozomu; Kishimoto, Shinji; Matsui, Shogo; Hashimoto, Haruki; Aibara, Yoshiki; Yusoff, Farina Mohamad; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Noma, Kensuke; Nakashima, Ayumu; Goto, Chikara; Hida, Eisuke; Higashi, Yukihito

2017-12-29

Flow-mediated vasodilation (FMD) of the brachial artery has been used for the assessment of endothelial function. Considering the mechanism underlying the vasodilatory response of the brachial artery to reactive hyperemia, hyperemic shear stress (HSS), a stimulus for FMD; nitroglycerine-induced vasodilation (NID), an index of endothelium-independent vasodilation; and baseline brachial artery diameter (BAD) are also involved in vasodilatory response. The purpose of this study was to investigate the interrelationships among FMD, HSS, NID, baseline BAD, and cardiovascular risk factors. We measured FMD, HSS, NID, and baseline BAD simultaneously in 1033 participants (633 men and 400 women; mean age: 58.6±17.0 years). Framingham risk score was negatively correlated with FMD, HSS, and NID and was positively correlated with baseline BAD. HSS and NID were positively correlated with FMD, and baseline BAD was negatively correlated with FMD. In participants with normal NID, FMD was correlated with HSS, NID, and baseline BAD, all of which were independent variables of FMD in multivariate analysis. In participants with impaired NID, FMD was correlated with NID and baseline BAD, both of which were independent variables of FMD in multivariate analysis, but there was no association between FMD and HSS. NID and baseline BAD were independent variables of FMD regardless of the status of endothelium-independent vasodilation, whereas there was a significant association between FMD and HSS in participants with normal NID but not in those with impaired NID. The influence of HSS on FMD seems to be dependent on the status of endothelium-independent vasodilation. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Forward and Backward Pressure Waveform Morphology in Hypertension.

PubMed

Li, Ye; Gu, Haotian; Fok, Henry; Alastruey, Jordi; Chowienczyk, Philip

2017-02-01

We tested the hypothesis that increased pulse wave reflection and altered backward waveform morphology contribute to increased pulse pressure in subjects with higher pulse pressure compared with lower pulse pressure and to actions of vasoactive drugs to increase pulse pressure. We examined the relationship of backward to forward wave morphology in 158 subjects who were evaluated for hypertension (including some normotensive subjects) divided into 3 groups by central pulse pressure: group 1, 33±6.5 mm Hg; group 2, 45±4.1 mm Hg; and group 3, 64±12.9 mm Hg (means±SD) and in healthy normotensive subjects during administration of inotropic and vasomotor drugs. Aortic pressure and flow in the aortic root were estimated by carotid tonometry and Doppler sonography, respectively. Morphology of the backward wave relative to the forward wave was similar in subjects in the lowest and highest tertiles of pulse pressure. Similar results were seen with the inotropic, vasopressor and vasodilator drugs, dobutamine, norepinephrine, and phentolamine, with the backward wave maintaining a constant ratio to the forward wave. However, nitroglycerin, a drug with a specific action to dilate muscular conduit arteries, reduced the amplitude of the backward wave relative to the forward wave from 0.26±0.018 at baseline to 0.19±0.019 during nitroglycerin 30 μg/min IV (P<0.01). These results are best explained by an approximately constant amount of reflection of the forward wave from the peripheral vasculature. The amount of reflection can be modified by dilation of peripheral muscular conduit arteries but contributes little to increased pulse pressure in hypertension. © 2016 The Authors.

Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort.

PubMed

Huffman, Mark D; Khalil, Anita; Osmond, Clive; Fall, Caroline H D; Tandon, Nikhil; Lakshmy, Ramakrishnan; Ramji, Siddharth; Gera, Tarun; Prabhakaran, Poornima; Dey Biswas, S K; Reddy, K Srinath; Bhargava, Santosh K; Sachdev, Harshpal S; Prabhakaran, Dorairaj

2015-12-01

Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI th > 30 kg/m [2] ). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function.

A density functional theory study of the decomposition mechanism of nitroglycerin.

PubMed

Pei, Liguan; Dong, Kehai; Tang, Yanhui; Zhang, Bo; Yu, Chang; Li, Wenzuo

2017-08-21

The detailed decomposition mechanism of nitroglycerin (NG) in the gas phase was studied by examining reaction pathways using density functional theory (DFT) and canonical variational transition state theory combined with a small-curvature tunneling correction (CVT/SCT). The mechanism of NG autocatalytic decomposition was investigated at the B3LYP/6-31G(d,p) level of theory. Five possible decomposition pathways involving NG were identified and the rate constants for the pathways at temperatures ranging from 200 to 1000 K were calculated using CVT/SCT. There was found to be a lower energy barrier to the β-H abstraction reaction than to the α-H abstraction reaction during the initial step in the autocatalytic decomposition of NG. The decomposition pathways for CHOCOCHONO 2 (a product obtained following the abstraction of three H atoms from NG by NO 2 ) include O-NO 2 cleavage or isomer production, meaning that the autocatalytic decomposition of NG has two reaction pathways, both of which are exothermic. The rate constants for these two reaction pathways are greater than the rate constants for the three pathways corresponding to unimolecular NG decomposition. The overall process of NG decomposition can be divided into two stages based on the NO 2 concentration, which affects the decomposition products and reactions. In the first stage, the reaction pathway corresponding to O-NO 2 cleavage is the main pathway, but the rates of the two autocatalytic decomposition pathways increase with increasing NO 2 concentration. However, when a threshold NO 2 concentration is reached, the NG decomposition process enters its second stage, with the two pathways for NG autocatalytic decomposition becoming the main and secondary reaction pathways.

Decreased frequency and duration of tooth brushing is a risk factor for endothelial dysfunction.

PubMed

Matsui, Shogo; Kajikawa, Masato; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Oda, Nozomu; Kishimoto, Shinji; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Nakashima, Ayumu; Noma, Kensuke; Taguchi, Akira; Higashi, Yukihito

2017-08-15

Periodontal disease is associated with endothelial dysfunction, leading to cardiovascular disease. The effect of detailed tooth brushing behavior, not only frequency but also duration of tooth brushing, on endothelial function is unclear. The purpose of this study was to evaluate the relationships of detailed methods of tooth brushing with vascular function. We evaluated flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation, and frequency and duration of tooth brushing in 896 subjects. We divided the subjects into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (

High-speed coronary rotational angioplasty with the rotablator

NASA Astrophysics Data System (ADS)

Zacca, Nadim M.; Kleiman, Neal S.; Asimacopoulos, P. J.

1992-08-01

Percutaneous mechanical rotational ablation with the rotablator can be used effectively as a stand alone treatment for coronary arterial lesions, including those with angiographic morphology considered unfavorable for balloon angioplasty (eccentric, at bends, bifurcating, calcified, ulcerated, completely occluded_, as well as for balloon angioplasty procedure failures. The use of single rather than multiple burrs without balloon assistance, the use of fewer passes and of the nitroglycerine infusion through the rotablator catheter have considerably shortened the time necessary to complete a rotational atherectomy. Further, the apparently infrequent occurrence of post procedure abrupt closure makes this technique attractive in the clinical management of patients with complex coronary artery lesions.

Gun Propellant Residues Dispersed from Static Artillery Firings of LG1 Mark 2 and C3 105-mm Howitzers

DTIC Science & Technology

2008-10-01

nitroglycerine (NG). In this study, aluminium witness plates were placed in front of the muzzle of the gun to collect residues propelled in the environment...témoins en aluminium ont été placées en face de la bouche du canon pour récolter les résidus de tirs propulsés dans l’environnement. Les plaques ont été...the Mark II and C3 105-mm howitzers, during an artillery exercise performed from May 9 to May 12, 2005 at CFB Gagetown in New-Brunswick. Aluminium

Hair combing to collect organic gunshot residues (OGSR).

PubMed

MacCrehan, William A; Layman, Malinda J; Secl, Janelle D

2003-08-12

A protocol is presented for the collection and analysis of gunshot residues (GSR) from hair. A fine-toothed comb is used for collection of the residues. A small zip-closure bag serves as a container for both sample storage and extraction of the characteristic organic powder additives. The success of this residue recovery approach was tested on simulated shooters and victims using mannequin-supported human wig hair as well as on human shooters. Residues were collected from four weapons: a revolver and semi-automatic pistol, rifle and shotgun. One characteristic additive, nitroglycerin, was detected by capillary electrophoresis (CE) in the majority of the collection experiments.

Voltammetric analysis of ordnance materials. Part 2: A portable digital voltammeter for use with a silver wire working electrode

NASA Astrophysics Data System (ADS)

Fine, D. A.; Reeve, D. A.; Dickus, R. A.

1984-12-01

An inexpensive, portable, digital voltammeter has been designed and built at NWC. The instrument is intended for use with a silver wire working electrode. The voltammeter was built in response to a need on the part of Navy facilities for the monitoring of effluent water from the carbon column cleanup process used to remove propyleneglycoldinitrate from Otto fuel waste water. The instrument may also be used for the monitoring of contaminants such as nitroglycerin, dinitrotoluene, trinitrotoluene and nitroguanidine. This report describes in detail the construction, circuitry, software and operational features of the instrument.

Agmatine: a novel endogenous vasodilator substance.

PubMed

Gao, Y; Gumusel, B; Koves, G; Prasad, A; Hao, Q; Hyman, A; Lippton, H

1995-01-01

The purpose of the study was to investigate the effects of agmatine, an endogenous clonidine-displacing substance (CDS), on systemic hemodynamics in the anesthetized rat. Bolus intravenous (i.v.) injections of agmatine decreased systemic arterial pressure (SAP) and systemic vascular resistance in a dose-dependent manner. The development of acute tachyphylaxis to the systemic vasodepressor response to agmatine did not induce cross-tachyphylaxis to the systemic vasodepressor responses to bradykinin, isoproterenol and nitroglycerin. The present data demonstrate agmatine, as a CDS and agonist for imidazoline (I) receptors, possesses marked systemic vasodilator activity in the rat. The present data suggest that activation of I receptors may represent a novel mechanism of vasodilation in vivo.

Endothelial microparticles and vascular parameters in subjects with and without arterial hypertension and coronary artery disease.

PubMed

Sansone, Roberto; Baaken, Maximilian; Horn, Patrick; Schuler, Dominik; Westenfeld, Ralf; Amabile, Nicolas; Kelm, Malte; Heiss, Christian

2018-08-01

Endothelial microparticles (EMPs) are markers of endothelial injury and activation. The role of EMPs in arterial hypertension is not well understood and EMPs are increased both in arterial hypertension and coronary artery disease (CAD). The data presented here show EMPs as defined by CD31 + /41 - , CD62e + , and CD144 + surface markers and vascular hemodynamic parameters including office and central blood pressure, heart rate, aortic augmentation index, pulse wave velocity, flow-mediated dilation, nitroglycerin-mediated dilation, brachial artery diameter, hyperemic wall shear stress, and laser Doppler perfusion of the cutaneous microcirculation of normotensives and hypertensives with and without CAD.

Solid tumor physiology and hypoxia-induced chemo/radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer.

PubMed

Yasuda, Hiroyasu

2008-09-01

Hypoxia exists in solid tumor tissues due to abnormal vasculature, vascular insufficiency, treatment or malignancy related anemia, and low intratumor blood flow. Hypoxic status in solid tumor promotes accumulation of hypoxia-inducible factor-1 alpha which is promptly degraded by proteasomal ubiquitination under normoxic conditions. However, under hypoxic conditions, the ubiquitination system for HIF-1 alpha is inhibited by inactivation of prolyl hydroxylase which is responsible for hydroxylation of proline in the oxygen-dependent degradation domain of HIF-1 alpha. HIF-1 alpha is an important transcriptional factor that codes for hundreds of genes involved in erythropoiesis, angiogenesis, induction of glycolytic enzymes in tumor tissues, modulation of cancer cell cycle, cancer proliferation, and cancer metastasis. Hypoxia and accumulation of HIF-1 alpha in solid tumor tissues have been reported to associate with resistance to chemotherapy, radiotherapy, and immunotherapy and poor prognosis. Production of vascular endothelial growth factor (VEGF) in cancer cells is regulated by the activated HIF-1 mediated system. An increase in VEGF levels subsequently induces HIF-1 alpha accumulation and promotes tumor metastasis by angiogenesis. Recently, angiogenesis targeting therapy using humanized VEGF antibody and VEGF receptor tyrosine kinase inhibitors have been used in solid cancer therapy. Nitric oxide (NO) is a unique chemical gaseous molecule that plays a role as a chemical messenger involved in vasodilator, neurotransmitter, and anti-platelet aggregation. In vivo, NO is produced and released from three different isoforms of NO synthase (NOS) and from exogenously administered NO donors. In cancer science, NO has been mainly discussed as an oncogenic molecule over the past decades. However, NO has recently been noted in cancer biology associated with cancer cell apoptosis, cancer cell cycle, cancer progression and metastasis, cancer angiogenesis, cancer chemoprevention, and modulator for chemo/radio/immuno-therapy. The presence and activities of all the three isoforms of NOS and were detected in cancer tissue components such as cancer cells, tumor-associated macrophages, and vascular endothelium. Overexpression of iNOS in cancer tissues has been reported to associate with poor prognosis in patients with cancers. On the other hand, NO donors such as nitroglycerin have been demonstrated to improve the effects of cancer therapy in solid cancers. Nitroglycerin has been used safely for a long time as a potent vasodilator for the treatment of ischemic heart diseases or heart failure. Therefore, we think highly of clinical use of nitroglycerin as a novel cancer therapy in combination with anticancer drugs for improvement of cancer therapeutic levels. In this review article, we demonstrate the unique physiological characteristics of malignant solid tumors, several factors in solid tumors resulting in resistance for cancer therapies, and the effects of NO from NOS or exogenous NO-donating drugs on malignant cells. Furthermore, we refer to promising therapeutic roles of NO and NO-donating drugs for novel treatments in solid tumors.

Nitrates for acute heart failure syndromes.

PubMed

Wakai, Abel; McCabe, Aileen; Kidney, Rachel; Brooks, Steven C; Seupaul, Rawle A; Diercks, Deborah B; Salter, Nigel; Fermann, Gregory J; Pospisil, Caroline

2013-08-06

Current drug therapy for acute heart failure syndromes (AHFS) consists mainly of diuretics supplemented by vasodilators or inotropes. Nitrates have been used as vasodilators in AHFS for many years and have been shown to improve some aspects of AHFS in some small studies. The aim of this review was to determine the clinical efficacy and safety of nitrate vasodilators in AHFS. To quantify the effect of different nitrate preparations (isosorbide dinitrate and nitroglycerin) and the effect of route of administration of nitrates on clinical outcome, and to evaluate the safety and tolerability of nitrates in the management of AHFS. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (1950 to July week 2 2011) and EMBASE (1980 to week 28 2011). We searched the Current Controlled Trials MetaRegister of Clinical Trials (compiled by Current Science) (July 2011). We checked the reference lists of trials and contacted trial authors. We imposed no language restriction. Randomised controlled trials comparing nitrates (isosorbide dinitrate and nitroglycerin) with alternative interventions (frusemide and morphine, frusemide alone, hydralazine, prenalterol, intravenous nesiritide and placebo) in the management of AHFS in adults aged 18 and over. Two authors independently performed data extraction. Two authors performed trial quality assessment. We used mean difference (MD), odds ratio (OR) and 95% confidence intervals (CI) to measure effect sizes. Two authors independently assessed and rated the methodological quality of each trial using the Cochrane Collaboration tool for assessing risk of bias. Four studies (634 participants) met the inclusion criteria. Two of the included studies included only patients with AHFS following acute myocardial infarction (AMI); one study excluded patients with overt AMI; and one study included participants with AHFS with and without acute coronary syndromes.Based on a single study, there was no significant difference in the rapidity of symptom relief between intravenous nitroglycerin/N-acetylcysteine and intravenous frusemide/morphine after 30 minutes (fixed-effect MD -0.30, 95% CI -0.65 to 0.05), 60 minutes (fixed-effect MD -0.20, 95% CI -0.65 to 0.25), three hours (fixed-effect MD 0.20, 95% CI -0.27 to 0.67) and 24 hours (fixed-effect MD 0.00, 95% CI -0.31 to 0.31). There is no evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following outcome measures: requirement for mechanical ventilation, systolic blood pressure (SBP) change after three hours and 24 hours, diastolic blood pressure (DBP) change after 30, 60 and 90 minutes, heart rate change at 30 minutes, 60 minutes, three hours and 24 hours, pulmonary artery occlusion pressure (PAOP) change after three hours and 18 hours, cardiac output (CO) change at 90 minutes and three hours and progression to myocardial infarction. There is a significantly higher incidence of adverse events after three hours with nitroglycerin compared with placebo (odds ratio 2.29, 95% CI 1.26 to 4.16) based on a single study. There was no consistent evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following secondary outcome measures: SBP change after 30 and 60 minutes, heart rate change after 90 minutes, and PAOP change after 90 minutes. None of the included studies reported healthcare costs as an outcome measure. There were no data reported by any of the studies relating to the acceptability of the treatment to the patients (patient satisfaction scores).Overall there was a paucity of relevant quality data in the included studies. Assessment of overall risk of bias in these studies was limited as three of the studies did not give sufficient detail to allow assessment of potential risk of bias. There appears to be no significant difference between nitrate vasodilator therapy and alternative interventions in the treatment of AHFS, with regard to symptom relief and haemodynamic variables. Nitrates may be associated with a lower incidence of adverse effects after three hours compared with placebo. However, there is a lack of data to draw any firm conclusions concerning the use of nitrates in AHFS because current evidence is based on few low-quality studies.

A Case of Cardiac Cephalalgia Showing Reversible Coronary Vasospasm on Coronary Angiogram

PubMed Central

Yang, YoungSoon; Jin, Dong Gyu; Jang, Il Mi; Jang, YoungHee; Na, Hae Ri; Kim, SanYun

2010-01-01

Background Under certain conditions, exertional headaches may reflect coronary ischemia. Case Report A 44-year-old woman developed intermittent exercise-induced headaches with chest tightness over a period of 10 months. Cardiac catheterization followed by acetylcholine provocation demonstrated a right coronary artery spasm with chest tightness, headache, and ischemic effect of continuous electrocardiography changes. The patient's headache disappeared following intra-arterial nitroglycerine injection. Conclusions A coronary angiogram with provocation study revealed variant angina and cardiac cephalalgia, as per the International Classification of Headache Disorders (code 10.6). We report herein a patient with cardiac cephalalgia that manifested as reversible coronary vasospasm following an acetylcholine provocation test. PMID:20607049

Outcomes of Physician-Staffed Versus Non-Physician-Staffed Helicopter Transport for ST-Elevation Myocardial Infarction.

PubMed

Gunnarsson, Sverrir I; Mitchell, Joseph; Busch, Mary S; Larson, Brenda; Gharacholou, S Michael; Li, Zhanhai; Raval, Amish N

2017-02-02

The effect of physician-staffed helicopter emergency medical service (HEMS) on ST-elevation myocardial infarction (STEMI) patient transfer is unknown. The purpose of this study was to evaluate the characteristics and outcomes of physician-staffed HEMS (Physician-HEMS) versus non-physician-staffed (Standard-HEMS) in patients with STEMI. We studied 398 STEMI patients transferred by either Physician-HEMS (n=327) or Standard-HEMS (n=71) for primary or rescue percutaneous coronary intervention at 2 hospitals between 2006 and 2014. Data were collected from electronic medical records and each institution's contribution to the National Cardiovascular Data Registry. Baseline characteristics were similar between groups. Median electrocardiogram-to-balloon time was longer for the Standard-HEMS group than for the Physician-HEMS group (118 vs 107 minutes; P=0.002). The Standard-HEMS group was more likely than the Physician-HEMS group to receive nitroglycerin (37% vs 15%; P<0.001) and opioid analgesics (42.3% vs 21.7%; P<0.001) during transport. In-hospital adverse outcomes, including cardiac arrest, cardiogenic shock, and serious arrhythmias, were more common in the Standard-HEMS group (25.4% vs 11.3%; P=0.002). After adjusting for age, sex, Killip class, and transport time, patients transferred by Standard-HEMS had increased risk of any serious in-hospital adverse event (odds ratio=2.91; 95% CI=1.39-6.06; P=0.004). In-hospital mortality was not statistically different between the 2 groups (9.9% in the Standard-HEMS group vs 4.9% in the Physician-HEMS group; P=0.104). Patients with STEMI transported by Standard-HEMS had longer transport times, higher rates of nitroglycerin and opioid administration, and higher rates of adjusted in-hospital events. Efforts to better understand optimal transport strategies in STEMI patients are needed. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting from chronic anal fissure: a randomized, double-blind, placebo-controlled study

PubMed Central

2013-01-01

Background Complications of chronic anal fissure (CAF) treatments are prompting interest in lower-risk therapies. This study was conducted to compare nitroglycerin (NTG) 0.4% ointment with placebo for pain associated with CAF. Methods In this randomized, double-blind, placebo-controlled trial, patients with one CAF and moderate-to-severe pain (≥50 mm on a 100 mm visual analog scale [VAS]) received 375 mg NTG 0.4% (1.5 mg active ingredient) or 375 mg placebo ointment applied anally every 12 hours for 21 days. The primary end point was change from baseline VAS score in 24-hour pain averaged over days 14–18. Review of data from patients who withdrew early was blinded to treatment. To control for the confounding effects of analgesics, all patients received 650 mg acetaminophen for headache prophylaxis before each application. Results A total of 247 patients were enrolled (NTG, n = 123; placebo, n = 124). The prespecified baseline observation carried forward (BOCF) analysis found no significant difference between groups; however, a last observation carried forward (LOCF) analysis showed a significant advantage for NTG. A post hoc analysis (LOCF/BOCF hybrid) demonstrated a significant adjusted mean difference of −7.0 mm in favor of NTG 0.4% (95% CI −13.6, –0.4; P = .038). Headache was the most common adverse event in the NTG (69.9%) and placebo (47.6%) groups. Conclusions This was the first placebo-controlled study that also controlled for the confounding effects of analgesics used to treat NTG-induced headache. In patients with moderate-to-severe CAF pain, NTG 0.4% ointment effectively reduced CAF pain compared with placebo. Trial registration ClinicalTrials.gov, NCT00522041 PMID:23815124

Utility of different outcome measures for the nitroglycerin model of migraine in mice.

PubMed

Farkas, Sándor; Bölcskei, Kata; Markovics, Adrienn; Varga, Anita; Kis-Varga, Ágnes; Kormos, Viktória; Gaszner, Balázs; Horváth, Csilla; Tuka, Bernadett; Tajti, János; Helyes, Zsuzsanna

2016-01-01

Majority of the work for establishing nitroglycerin (NTG)-induced migraine models in animals was done in rats, though recently some studies in mice were also reported. Different special formulations of NTG were investigated in various studies; however, NTG treated groups were often compared to simple saline treated control groups. The aim of the present studies was to critically assess the utility of a panel of potential outcome measures in mice by revisiting previous findings and investigating endpoints that have not been tested in mice yet. We investigated two NTG formulations, Nitrolingual and Nitro Pohl, at an intraperitoneal dose of 10mg/kg, in comparison with relevant vehicle controls, and evaluated the following outcome measures: light aversive behaviour, cranial blood perfusion by laser Doppler imaging, number of c-Fos- and neuronal nitrogen monoxide synthase (nNOS)-immunoreactive neurons in the trigeminal nucleus caudalis (TNC) and trigeminal ganglia, thermal hyperalgesia and tactile allodynia of the hind paw and orofacial pain hypersensitivity. We could not confirm previous reports of significant NTG-induced changes in light aversion and cranial blood perfusion of mice but we observed considerable effects elicited by the vehicle of Nitrolingual. In contrast, the vehicle of Nitro Pohl was apparently inert. Increased c-Fos expression in the TNC, thermal hyperalgesia, tactile allodynia and orofacial hypersensitivity were apparently good endpoints in mice that were increased by NTG-administration. The NTG-induced increase in c-Fos expression was prevented by topiramate but not by sumatriptan treatment. However, the NTG-induced orofacial hypersensitivity was dose dependently attenuated by sumatriptan. Our results pointed to utilisable NTG formulations and outcome measures for NTG-induced migraine models in mice. Pending further cross-validation with positive and negative control drugs in these mouse models and in the human NTG models of migraine, these tests might be valuable translational research tools for development of new anti-migraine drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

Regular Aerobic, Resistance, and Cross-Training Exercise Prevents Reduced Vascular Function Following a High Sugar or High Fat Mixed Meal in Young Healthy Adults

PubMed Central

Das, Emon K.; Lai, Pui Y.; Robinson, Austin T.; Pleuss, Joan; Ali, Mohamed M.; Haus, Jacob M.; Gutterman, David D.; Phillips, Shane A.

2018-01-01

The postprandial state can negatively influence flow mediated dilation (FMD), a predictor of atherosclerosis and cardiovascular disease. This investigation was designed to determine the effect of regular aerobic and/or resistance exercise on postprandial FMD after a high sugar or high fat mixed meal. Forty-five healthy participants were recruited from one of four groups: lean sedentary (SED), runners, weight lifters, and cross-trainers. Participants were randomly crossed over to a high sugar meal (HSM) and a high fat mixed meal (HFMM; both fat and carbohydrate). Pre-and postprandial endothelial function was assessed for both meals using brachial artery FMD. Plasma lipids, insulin, glucose, hs-CRP, and SOD were also measured with both meals. Endothelium-independent dilation was determined via sublingual nitroglycerin. Brachial artery FMD was reduced in SED following the HSM (9.9 ± 0.9% at baseline, peak reduction at 60 min 6.5 ± 1.0%) and the HFMM (9.4 ± 0.9% at baseline, peak reduction at 120 min 5.9 ± 1.2%; P < 0.05 for both, Mean ± SEM). There was no change in FMD after either HSM or HFMM in runners, weight lifters, and cross-trainers. Post-prandial increases in blood glucose, insulin and triglycerides were less pronounced in the exercisers compared to SED. In addition, exercisers presented lower baseline plasma hs-CRP and higher SOD activity. Nitroglycerin responses were similar among groups. These results suggest that endothelial function is reduced in sedentary adults after a HSM or HFMM, but not in regular aerobic or resistance exercisers. This response may be due to favorable postprandial metabolic responses or lower postprandial levels of inflammation and oxidative stress. These findings may help to explain the cardioprotective effect of exercise. PMID:29568273

Sodium nitroglycerin induces middle cerebral artery vasodilation in young, healthy adults.

PubMed

Schulz, Jenna M; Al-Khazraji, Baraa K; Shoemaker, J Kevin

2018-05-15

Recent evidence indicates that basal cerebral conduit vessels dilate with hypercapnia, with a nitric oxide (NO) mechanism explaining one way in which parenchymal cerebral arterioles dilate. However, whether NO affects basal cerebral artery dilation remains unknown. This study quantified the effect of an exogenous NO donor [sodium nitroglycerin (NTG); 0.4 mg sublingual spray] on the right middle cerebral artery (rMCA) cross-sectional area (CSA), blood velocity and overall blood flow. Measures of vessel CSA (7 Tesla magnetic resonance imaging) and MCA blood velocity (transcranial Doppler ultrasound) were made at baseline (BL), and following exogenous NTG or placebo (PLO) administration in young, healthy individuals (n = 10, 2 males, age range 20-23 years). CSA increased in the rMCA [BL: 5.2 ± 1.2 mm 2 ; PLO: 5.4 ± 1.5 mm 2 ; NTG: 6.6 ± 1.5 mm 2 , P < 0.05; mean ± SD]. Concurrently, rMCA blood velocity decreased from BL during NTG, compared to PLO (BL: 67 ± 10 cm s -1 ; PLO: 62 ± 10 cm s -1 ; NTG: 59 ± 9.3 cm s -1 , P < 0.05; mean ± SD]. However, total MCA blood flow did not change with NTG or PLO [BL: 221 ± 37.4 mL min -1 ; PLO: 218 ± 35.0 mL min -1 ; NTG: 213 ± 46.4 mL min -1 ). Therefore, exogenous NO mediates a dilatory response in the rMCA, but not in its downstream vascular bed. This article is protected by copyright. All rights reserved. © 2018 The Authors Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Effects of prehospital nitroglycerin on hemodynamics and chest pain intensity.

PubMed

Engelberg, S; Singer, A J; Moldashel, J; Sciammarella, J; Thode, H C; Henry, M

2000-01-01

To assess the effects of prehospital nitroglycerin (NTG) on vital signs and chest pain intensity. A retrospective review of advanced life support (ALS) run sheets was performed in a suburban volunteer emergency medical services (EMS) system receiving 8,000 annual ALS calls. All consecutive patients who were administered NTG by EMS were included. Standardized forms were used to collect data on patient demographics, history, and physical exam. Patients assessed their chest pain (CP) before and after NTG on a verbal numeric scale of 0-10 from least to most severe. The presence of syncope, dysrhythmias, or profound hypotension [loss of peripheral pulses, a systolic blood pressure (SBP) of <90 mm Hg after NTG, or a drop of >100 mm Hg in BP] was noted. Results. One thousand six hundred sixty-two patients received NTG over 18 months, their mean age was 66 years, and 48% were female. Indications for NTG included CP (83%), dyspnea (45%), and congestive heart failure (20%). After NTG administration, the CP score decreased from 6.9 to 4.4 (mean difference = 2.6; 95% CI = 2.4 to 2.8). The CP completely resolved in 10% of the patients. Mean decreases in SBPs and diastolic BPs were 11.8 mm Hg (95% CI = 10.7 to 13.0) and 4.0 mm Hg (95% CI = 2.9 to 5.1). The mean pulse rate increased by 2.7 beats/min (95% CI = 0.6 to 4.9). There were 12 patients with adverse events [0.7% (95% CI = 0.4% to 1.3%)], including profound bradycardia and hypotension (1), transient drop in SBP of 100 mm Hg responding to fluids (6), post-NTG SBP <90 mm Hg (4), and syncope (1). There were no deaths in the prehospital setting. Use of prehospital NTG appears safe. While NTG reduces CP, most patients have residual pain.

Spinal Cord Stimulation for Refractory Angina Pectoris

PubMed Central

Bao, Hongguang; Si, Yanna; Xu, Chenjie; Chen, Hao; Gao, Xianzhong; Xie, Xinyi; Xu, Yajie; Sun, Fan; Zeng, Lingqing

2017-01-01

Objectives: Paresthesia-free stimulation such as high frequency and burst have been demonstrated as effective therapies for neuropathic pain. The aim of this meta-analysis was to evaluate the efficacy and safety of conventional spinal cord stimulation (SCS) in the treatment of refractory angina pectoris (RAP). Materials and Methods: Relevant randomized controlled trials that investigated SCS for patients with RAP were comprehensively searched in Medline, Pubmed, Embase, and Cochrane Library. Five meta-analyses were performed examining the changes in Canadian Cardiovascular Society classes, exercise time, Visual Analog Scale (VAS) scores of pain, Seattle Angina Questionnaire, and nitroglycerin use in RAP patients after SCS therapy. We analyzed standardized mean differences (MD) and 95% confidence intervals (CIs) for each outcome by Review Manager 5.0 and STATA 12.0. Results: A total of 12 randomized controlled trials involving 476 RAP patients were identified. A trend of reduction in the angina frequency (MD=−9.03, 95% CI, −15.70 to −2.36) and nitroglycerin consumption (MD=−0.64, 95% CI, −0.84 to −0.45) could be observed in the SCS group. Compared with the control group, SCS showed benefit on increasing exercise time (MD=0.49, 95% CI, 0.13-0.85) and treatment satisfaction (MD=6.87, 95% CI, 2.07-11.66) with decreased VAS scores of pain (MD=−0.50, 95% CI, −0.81 to −0.20) and disease perception (MD=−8.34, 95% CI, −14.45 to −2.23). However, the result did not reach the significance level in terms of physical limitation (95% CI, −8.75 to 3.38; P=0.39) or angina stability (95% CI, −7.55 to 3.67; P=0.50). Discussion: The current meta-analysis suggested that SCS was a potential alternative in the treatment of PAP patients. Further investigation for finding the appropriate intensity of stimulation is required before this treatment should be widely recommended and applied. PMID:27875377

Spinal Cord Stimulation for Refractory Angina Pectoris: A Systematic Review and Meta-analysis.

PubMed

Pan, Xiaoxiao; Bao, Hongguang; Si, Yanna; Xu, Chenjie; Chen, Hao; Gao, Xianzhong; Xie, Xinyi; Xu, Yajie; Sun, Fan; Zeng, Lingqing

2017-06-01

Paresthesia-free stimulation such as high frequency and burst have been demonstrated as effective therapies for neuropathic pain. The aim of this meta-analysis was to evaluate the efficacy and safety of conventional spinal cord stimulation (SCS) in the treatment of refractory angina pectoris (RAP). Relevant randomized controlled trials that investigated SCS for patients with RAP were comprehensively searched in Medline, Pubmed, Embase, and Cochrane Library. Five meta-analyses were performed examining the changes in Canadian Cardiovascular Society classes, exercise time, Visual Analog Scale (VAS) scores of pain, Seattle Angina Questionnaire, and nitroglycerin use in RAP patients after SCS therapy. We analyzed standardized mean differences (MD) and 95% confidence intervals (CIs) for each outcome by Review Manager 5.0 and STATA 12.0. A total of 12 randomized controlled trials involving 476 RAP patients were identified. A trend of reduction in the angina frequency (MD=-9.03, 95% CI, -15.70 to -2.36) and nitroglycerin consumption (MD=-0.64, 95% CI, -0.84 to -0.45) could be observed in the SCS group. Compared with the control group, SCS showed benefit on increasing exercise time (MD=0.49, 95% CI, 0.13-0.85) and treatment satisfaction (MD=6.87, 95% CI, 2.07-11.66) with decreased VAS scores of pain (MD=-0.50, 95% CI, -0.81 to -0.20) and disease perception (MD=-8.34, 95% CI, -14.45 to -2.23). However, the result did not reach the significance level in terms of physical limitation (95% CI, -8.75 to 3.38; P=0.39) or angina stability (95% CI, -7.55 to 3.67; P=0.50). The current meta-analysis suggested that SCS was a potential alternative in the treatment of PAP patients. Further investigation for finding the appropriate intensity of stimulation is required before this treatment should be widely recommended and applied.

The efficacy of trimetazidine on stable angina pectoris: a meta-analysis of randomized clinical trials.

PubMed

Peng, Song; Zhao, Min; Wan, Jing; Fang, Qi; Fang, Dong; Li, Kaiyong

2014-12-20

This meta-analysis aimed to evaluate the efficacy of trimetazidine in combination with other anti-anginal drugs versus other anti-anginal drugs in the treatment of stable angina pectoris (SAP). Randomized controlled trials (RCTs) published in English and Chinese were retrieved from computerized databases: Embase, PubMed, and CNKI. Primary outcomes consist of clinical parameters (numbers of weekly angina attacks and nitroglycerin use) and ergometric parameters (time to 1mm ST-segment depression, and total work (in Mets) and exercise duration (in seconds) at peak exercise) in stable angina pectoris treated by trimetazidine or not. The quality of studies was evaluated using Jadad score. Data analysis of 13 studies was performed using Stata 12.0 software. Results showed that treatment of trimetazidine and other anti-anginal drugs was associated with a smaller weekly mean number of angina attacks (WMD=-0.95, 95%CI: -1.30 to -0.61, Z=5.39, P<0.001), fewer weekly nitroglycerin use (WMD=-0.98, 95%CI: -1.44 to -0.52, Z=4.19, P<0.001), longer time to 1mm ST-segment depression (WMD=0.30, 95%CI: 0.17 to 0.43, Z=4.46, P<0.001), higher total work (WMD=0.82, 95%CI: 0.44 to 1.20, Z=4.22, P<0.001) and longer exercise duration at peak exercise (WMD=49.81, 95%CI: 15.04 to 84.57, Z=6.38, P<0.001) than treatment of other anti-anginal drugs for stable angina pectoris. Sensitivity analysis was performed. Sub-group analysis showed that treatment duration was not a significant moderator and patients treated within 8 weeks and above 12 weeks had no difference in the outcomes addressed in this meta-analysis. No publish bias was detected. This meta-analysis confirms the efficacy of trimetazidine in the treatment of stable angina pectoris, in comparison with conventional antianginal agents, regardless of treatment duration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Comparison of Enhancement of Analgesic Effect of Intrathecal Neostigmine by Intrathecal Clonidine and Transdermal Nitroglycerin Patch on Bupivacaine Spinal Anesthesia.

PubMed

Mammen, Mathew V; Tripathi, Manoj; Chandola, Harish C; Tyagi, Amit; Bais, Prateek Singh; Sanjeev, Om Prakash

2017-01-01

Relief of pain is very important goal intraoperatively and postoperatively. Neostigmine has been used successfully intrathecally with other agents such as clonidine and opioids for pain relief. This study aims to compare and evaluate the efficacy and safety of combining intrathecal (IT) neostigmine with IT clonidine and transdermal nitroglycerin (tNTG) patch for the relief of pain in patients after surgery. This was a randomized, prospective, and comparative study. In this study, recruited patients were randomly allocated into three groups. Groups I, II, and III received intrathecally 25 μg of neostigmine + 15 mg hyperbaric 0.5% bupivacaine, 25 μg of neostigmine + 25 μg clonidine + 15 mg hyperbaric 0.5% bupivacaine, and 25 μg of neostigmine + tNTG patch (3 cm × 5 cm, 5 mg/24 h) +15 mg hyperbaric 0.5% bupivacaine, respectively. Heart rate, mean arterial pressure, analgesic properties, and complications were assessed and compared among groups. Mean and standard deviation were calculated. Test of analysis between two groups was done by t -test and among three groups by ANOVA, then P value was calculated. Duration of analgesia was significantly longer in Group III in comparison to Group II (7.142 ± 1.81 vs. 4.408 ± 0.813 h) and was significantly longer in Group II in comparison to Group I (4.408 ± 0.813 vs. 2.583 ± 0.493 h). Analgesic requirement was significantly less in Group III in comparison to Group II (1.9 ± 0.76 vs. 2.5 ± 0.51) and was significantly less in Group II in comparison to Group I (2.5 ± 0.51 vs. 3.1 ± 0.48). Sedation score was found significantly high in Group II than other groups. Both IT clonidine and tNTG patch with bupivacaine + neostigmine spinal anesthesia were found effective in pain control. Results were found better with tNTG patch.

Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort

PubMed Central

Huffman, Mark D.; Khalil, Anita; Osmond, Clive; Fall, Caroline H. D.; Tandon, Nikhil; Lakshmy, Ramakrishnan; Ramji, Siddharth; Gera, Tarun; Prabhakaran, Poornima; Dey Biswas, S. K.; Reddy, K. Srinath; Bhargava, Santosh K.; Sachdev, Harshpal S.; Prabhakaran, Dorairaj

2015-01-01

Background & objectives: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. Methods: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. Results: The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI > 30 kg/m2). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. Interpretation & conclusions: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function. PMID:26831418

Relation of Mitochondrial Oxygen Consumption in Peripheral Blood Mononuclear Cells to Vascular Function in Type 2 Diabetes Mellitus

PubMed Central

Hartman, Mor-Li; Shirihai, Orian S.; Holbrook, Monika; Xu, Guoquan; Kocherla, Marsha; Shah, Akash; Fetterman, Jessica L.; Kluge, Matthew A.; Frame, Alissa A.; Hamburg, Naomi M.; Vita, Joseph A.

2014-01-01

Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMC’s) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to ATP production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMC’s that would correlate with endothelial dysfunction. We developed a method to measure oxygen consumption in freshly isolated PBMC’s and applied it to 26 patients with type 2 diabetes mellitus and 28 non-diabetic controls. Basal (192±47 vs. 161±44 pMoles/min, P=0.01), uncoupled (64±16 vs. 53±16 pMoles/min, P=0.007), and maximal (795±87 vs. 715±128 pMoles/min, P=0.01) oxygen consumption rates were higher in diabetic patients compared to controls. There were no significant correlations between oxygen consumption rates and endothelium-dependent flow-mediated dilation measured by vascular ultrasound. Non-endothelium-dependent nitroglycerin-mediated dilation was lower in diabetics (10.1±6.6 vs. 15.8±4.8%, P=0.03) and correlated with maximal oxygen consumption (R= −0.64, P=0.001). In summary, we found that diabetes mellitus is associated with a pattern of mitochondrial oxygen consumption consistent with higher production of reactive oxygen species. The correlation between oxygen consumption and nitroglycerin-mediated dilation may suggest a link between mitochondrial dysfunction and vascular smooth muscle cell dysfunction that merits further study. Finally, the described method may have utility for assessment of mitochondrial function in larger scale observational and interventional studies in humans. PMID:24558030

Portable sensors for drug and explosive detection

NASA Astrophysics Data System (ADS)

Leginus, Joseph M.

1994-03-01

Westinghouse Electric is developing portable, hand-held sensors capable of detecting numerous drugs of abuse (cocaine, heroin, amphetamines) and explosives (trinitrotoluene, pentaerythritol tetranitrate, nitroglycerin). The easy-to-use system consists of a reusable electronics module and disposable probes. The sensor illuminates and detects light transmitted through optical cells of the probe during an antibody-based latex agglutination reaction. Each probe contains all the necessary reagents to carry out a test in a single step. The probe has the ability to lift minute quantities of samples from a variety of surfaces and deliver the sample to a reaction region within the device. The sensor yields a qualitative answer in 30 to 45 seconds and is able to detect illicit substances at nanogram levels.

Symposium on Explosives and Pyrotechnics, 13th, Hilton Head Island, SC, Dec. 2-4, 1986, Proceedings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-01-01

The present conference on explosive and pyrotechnic technologies discusses the shock-sensitivity of RDX, the thermodynamic properties of RDX, TNT, nitroglycerine, and HMX energetic molecules, the dynamic resistivity of exploding conductors, the decomposition of azides, the critical shock-initiation energy of emulsion explosives, actuator valve optimization, pyrotechnic aerosolization from novel imbibed liquid matrices, tetrazole initiators, and polymeric binders for red phosphorus pellets. Also discussed are channel-effect studies, the dynamic desensitization of coal mine explosives, the electromagnetic and electrostatic protection of explosives, the reliability of fuze explosive trains, the hazardous properties of explosive chemicals, the emulsification of an explosive with a chemical foamingmore » agent, and low energy ignition of HMX using a foil bridge.« less

Cutaneous heat flow during heating and cooling in Alligator mississipiensis.

PubMed

Smith, E N

1976-05-01

Direct in vivo measurement of heat flow across the skin of the American alligator (Alligator mississipiensis) showed increased heat flow during warming. Mean values at 25 degrees C during warming (15-35 degrees C) in air (airspeed 300 cm/s) were 17.9 +/- 92 SE cal/cm2 per h (mean alligator wt 3.27 kg). Cooling heat flow at the same temperature was 13.6 +/- 0.57 cal/cm2 per h. Subdermal heat flow was reduced during warming and was not significantly different from cutaneous heat flow during cooling. This indicated that the alligator was able to control its rate of heat exchange with the environment by altering cutaneous perfusion. Atropine, phenoxybenzamine, nitroglycerin, and Xylocaine did not affect cutaneous heat flow or heating and cooling rates. Atropine blocked bradycardia during cooling.

Monitoring underwater explosions in the habitat of resident bottlenose dolphins.

PubMed

dos Santos, Manuel E; Couchinho, Miguel N; Rita Luís, Ana; Gonçalves, Emanuel J

2010-12-01

Maintenance work on the harbor of Setúbal, in Portugal, required the removal of a 14-m deep rocky outcrop at the ship maneuver area, using about 35 kg of Gelamonite, a nitroglycerin-based high-explosive. This important harbor is located in the Sado estuary, a biologically rich environment and an important feeding area for a resident community of bottlenose dolphins. Using different safe range calculation models, a mitigation and monitoring plan was developed that minimized the risks of these underwater explosions for the dolphins. At our monitoring station, at 2 km from the demolition site, acoustic pressure levels in excess of 170 dB re 1 μPa (root-mean-square) were measured. Samples of dead fish collected at the site were indicative of shock trauma from the blasts.

Mid-term Risk for Subclinical Atherosclerosis and Chronic Myocarditis in Children with Kawasaki Disease and Transient Coronary Abnormalities.

PubMed

Parihar, Mansingh; Singh, Surjit; Vignesh, Pandiarajan; Gupta, Anju; Rohit, Manojkumar

2017-08-01

There is evidence for premature atherosclerosis and systemic arterial stiffening during follow-up of children with Kawasaki disease (KD) and coronary artery abnormalities (CAA). Moreover, patients with KD may also have subclinical myocardial involvement and inhomogeneous ventricular repolarization. The inhomogeneous ventricular repolarization manifests as increased QT dispersion on electrocardiography. There is a paucity of studies in endothelial dysfunction and QT dispersion in children with KD and transient CAA. Twenty children with KD and transient CAA were studied at least 1 year after resolution of CAA. Mean follow-up period between KD onset and enrolment in the study was 53.7 months. Twenty age and sex-matched controls were enrolled. High-resolution B-mode ultrasonography was used to analyze brachial artery dilatation in response to reactive hyperemia (cases and controls) and sublingual nitroglycerine (cases only). Carotid artery intima-media thickness (cIMT) and stiffness index were calculated. The difference between maximum and minimum QTc intervals on 12 lead electrocardiogram was calculated as QTc dispersion (QTcd). No statistically significant difference was noted in percent flow-mediated dilatation of brachial arteries in response to reactive hyperemia between cases (13.31 ± 10.41%) and controls (12.86 ± 7.09%). Sublingual nitroglycerine-mediated dilatation in children with KD was 14.88 ± 12.03%. Mean cIMT was similar in cases (0.036 ± 0.015 cm) and controls (0.035 ± 0.076 cm; p = 0.791). No statistically significant difference between groups was observed in mean QTcd values (0.057 ± 0.018 s vs. 0.059 ± 0.015 s in controls, p = 0.785). No evidence of significant endothelial dysfunction or increased QT dispersion in patients with KD and transient coronary artery abnormalities was found in our cohort when studied at a mean follow-up of 53.7 months. This is reassuring, and indicates that risk of subclinical atherosclerosis and myocarditis in a subset of children with KD and transient coronary artery abnormalities is not significant.

Efficacy of prophylactic doses of intravenous nitroglycerin in preventing myocardial ischemia under general anesthesia: A systematic review and meta-analysis with trial sequential analysis.

PubMed

Hoshijima, Hiroshi; Denawa, Yohei; Mihara, Takahiro; Takeuchi, Risa; Kuratani, Norifumi; Mieda, Tsutomu; Iwase, Yoshinori; Shiga, Toshiya; Wajima, Zen'ichiro; Nagasaka, Hiroshi

2017-08-01

To evaluate the efficacy of intravenous nitroglycerin (TNG) in preventing intraoperative myocardial ischemia (MI) under general anesthesia. Moreover, we analyzed the hemodynamic changes in heart rate (HR), mean blood pressure (MBP), and pulmonary capillary wedge pressure (PCWP) associated with TNG administration both before and after the induction of anesthesia. Meta-analysis. Operating room, cardiac surgery or non-cardiac surgery, all surgeries were elective measurements. We performed a computerized search of articles on PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using Review Manager. The data from the individual trials were combined using a random-effects model to calculate either the pooled relative risk (RR) or the weighted mean difference (WMD) with 95% confidence interval (CI). We conducted trial sequential analysis (TSA). The primary outcome was the incidence of MI and the secondary outcomes were hemodynamic changes (HR, MBP, and PCWP). Using electronic databases, we selected 10 trials with a total of 353 patients for our review. Prophylactic intravenous TNG did not significantly decrease the incidence of MI (RR=0.61; CI, 0.33 to 1.13; P=0.12; I 2 =55). TSA corrected the CI to 0.05 to 7.39 and showed that 9.5% of the required information size was achieved. In terms of hemodynamic changes, intravenous TNG significantly reduced MBP in comparison with the placebo (MBP pre-induction: WMD=-7.27; 95% CI -14.2 to -0.33; P=0.04; I 2 =97%; MBP post-induction: WMD=-5.13; 95% CI -9.17 to -1.09; P=0.01; I 2 =73%). Our analyses showed that prophylactic intravenous TNG does not reduce the incidence of intraoperative MI. Moreover, TSA suggests that further studies are necessary to confirm the results (GRADE: very low). Prophylactic doses of intravenous TNG significantly reduced the MBP both pre and post anesthesia induction (GRADE: very low). Copyright © 2017 Elsevier Inc. All rights reserved.

The influence of nitroglycerin on the proliferation of endothelial progenitor cells from peripheral blood of patients with coronary artery disease.

PubMed

Wang, Xin; Zeng, Caiyu; Gong, Huiping; He, Hong; Wang, Mengxin; Hu, Qin; Yang, Falin

2014-10-01

Endothelial progenitor cells (EPCs) are associated with vascular repairing and progression of atherosclerotic lesion. It may lead to coronary artery disease (CAD) if circulating EPCs lose their function. Continuous nitroglycerin (NTG) therapy causes increased vascular oxidative stress and endothelial dysfunction. The aim of this study was to investigate the effects of NTG on the proliferation of human peripheral blood-derived EPCs. EPC cultures, collected from 60 CAD patients and cultured for 7-12 days, were treated with different concentrations of NTG (0.0, 0.3, 1.0, 2.0, 7.5, 15.0, and 20.0 mg/l) for 72 h, respectively. The cell counts and proliferative activities of EPC; the levels of vascular endothelial growth factor-A (VEGF-A), nitric oxide (NO) and peroxynitrite (ONOO(-)) in culture medium; and the level of reactive oxygen species (ROS) in adherent cells were measured. Compared with control (0.0 mg/l NTG), the cell number and proliferative activities of EPCs were increased when treated with 1.0 mg/l NTG and reached maximum level when NTG concentration was 7.5 mg/l. However, there was a significant reduction when treated with higher doses of NTG (≥15.0 mg/l). Meanwhile, VEGF-A expression reached its maximal expression with 7.5 mg/l NTG, but gradually declined by incubation with higher doses of NTG. There was a linear relationship between NO level and NTG concentration, but no changes of ONOO(-) and ROS levels were found when EPCs were incubated with 0.3-7.5 mg/l NTG. However, ONOO(-) and ROS levels were significantly increased when incubated with 15 and 20 mg/l NTG. Our data demonstrated that moderate dose of NTG may stimulate the proliferative activities of EPCs isolated from CAD patients. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Nitroglycerine and patient position effect on central, hepatic and portal venous pressures during liver surgery.

PubMed

Sand, L; Lundin, S; Rizell, M; Wiklund, J; Stenqvist, O; Houltz, E

2014-09-01

To reduce blood loss during liver surgery, a low central venous pressure (CVP) is recommended. Nitroglycerine (NG) with its rapid onset and offset can be used to reduce CVP. In this study, the effect of NG on portal and hepatic venous pressures (PVP and HVP) in different body positions was assessed. Thirteen patients undergoing liver resection were studied. Cardiac output (CO), mean arterial pressure (MAP) and CVP were measured. PVP and HVP were measured using tip manometer catheters at baseline (BL) in horizontal position; during NG infusion, targeting a MAP of 60 mmHg, with NG infusion and the patient placed in 10 head-down position. NG infusion reduced HVP from 9.7 ± 2.4 to 7.2 ± 2.4, PVP from 12.3 ± 2.2 to 9.7 ± 3.0 and CVP from 9.8 ± 1.9 to 7.2 ± 2.1 mmHg at BL. Head-down tilt during ongoing NG resulted in increases in HVP to 8.2 ± 2.1, PVP to 10.7 ± 3 and CVP to 11 ± 1.9 mmHg. CO at BL was 6.3 ± 1.1, which was reduced by NG to 5.8 ± 1.2. Head-down tilt together with NG infusion restored CO to 6.3 ± 1.0 l/min. NG infusion leads to parallel reductions in CVP, HVP and PVP at horizontal body position. Thus, CVP can be used to guide NG dosage and fluid administration at horizontal position. NG infusion can be used to reduce HVP. Head-down tilt can be used during NG infusion to improve both blood pressure and CO without substantial increase in liver venous pressure. In head-down tilt, CVP dissociates from HVP and PVP. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

A short history of nitroglycerine and nitric oxide in pharmacology and physiology.

PubMed

Marsh, N; Marsh, A

2000-04-01

1. Nitroglycerine (NG) was discovered in 1847 by Ascanio Sobrero in Turin, following work with Theophile-Jules Pelouze. Sobrero first noted the 'violent headache' produced by minute quantities of NG on the tongue. 2. Constantin Hering, in 1849, tested NG in healthy volunteers, observing that headache was caused with 'such precision'. Hering pursued NG ('glonoine') as a homeopathic remedy for headache, believing that its use fell within the doctrine of 'like cures like'. 3. Alfred Nobel joined Pelouze in 1851 and recognized the potential of NG. He began manufacturing NG in Sweden, overcoming handling problems with his patent detonator. Nobel suffered acutely from angina and was later to refuse NG as a treatment. 4. During the mid-19th century, scientists in Britain took an interest in the newly discovered amyl nitrite, recognized as a powerful vasodilator. Lauder Brunton, the father of modern pharmacology, used the compound to relieve angina in 1867, noting the pharmacological resistance to repeated doses. 5. William Murrell first used NG for angina in 1876, although NG entered the British Pharmacopoeia as a remedy for hypertension. William Martindale, the pharmaceutical chemist, prepared '...a more stable and portable preparation': 1/100th of a grain in chocolate. 6. In the early 20th century, scientists worked on in vitro actions of nitrate-containing compounds although little progress was made towards understanding the cellular mode of action. 7. The NG industry flourished from 1900, exposing workers to high levels of organic nitrites; the phenomena of nitrate tolerance was recognized by the onset of 'Monday disease' and of nitrate-withdrawal/overcompensation by 'Sunday Heart Attacks'. 8. Ferid Murad discovered the release of nitric oxide (NO) from NG and its action on vascular smooth muscle (in 1977). Robert Furchgott and John Zawadski recognized the importance of the endothelium in acetylcholine-induced vasorelaxation (in 1980) and Louis Ignarro and Salvador Moncada identified endothelial-derived relaxing factor (EDRF) as NO (in 1987). 9. Glycerol trinitrate remains the treatment of choice for relieving angina; other organic esters and inorganic nitrates are also used, but the rapid action of NG and its established efficacy make it the mainstay of angina pectoris relief.

[Impacts on neutrophil to lymphocyte ratio in patients of chronic stable angina pectoris treated with acupuncture at Neiguan (PC 6)].

PubMed

Wang, Momg; Chen, Hui; Lu, Shengfeng; Wang, Jianfei; Zhang, Wei; Zhu, Bingmei

2015-05-01

To observe the clinical efficacy on chronic stable angina pectoris treated with acupuncture at Neiguan (PC 6) and explore the impacts of acupuncture on peripheral blood neutrophil to lymphocyte ratio (NLR) in the patients of stable angina pectoris. Thirty patients of chronic stable angina pectoris met the inclusive criteria were randomized into an acupuncture group (15 cases) and a medication group (15 cases), and a healthy control group (15 cases of the same ages) was set up separately. In the acupuncture group, at the same time of the basic medication, acupuncture was applied to bilateral Neiguan (PC 6), once every two days, 3 days a week, totally for 4 weeks. In the medication group, the basic medication was applied, without acupuncture intervention. In the healthy control group, no any intervention was applied. The attack frequency of angina pectoris, dose of nitrogly-cerin, the evaluation of visual analogue scale (VAS), Seattle angina questionnaire (SAQ), the six-minute walking test (6MWT), the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were observed before and after treatment in the subjects. Additionally, the peripheral blood cells were detected to analyze specifically the changes in NLR before and after treatment and observe the relationship between NLR and clinical efficacy. Compared with the medication group, the attack frequency of angina pectoris was reduced within 30 days (P<0.01); the dose of nitroglycerin was reduced (P<0.01); VAS was reduced (P<0.01) and SAQ was increased (P<0.05) in the acupuncture group. The differences in 6 MWT, SAS and SDS were not significant between the two groups after treatment (all P>0.05). Additionally, compared with the medication group, in 30 days of acupuncture, NLR was reduced apparently in the acupuncture group (P<0.05). Acupuncture relieves the clinical symptoms of chronic stable angina pectoris, but has not apparent effects on motor ability and psychological health. Corresponding to that before treatment, the decreased NRL in the patients of acupuncture group suggests the potential good prognosis on coronary heart disease after acupuncture.

Studies of vascular tolerance to nitroglycerin: effects of N-acetylcysteine, NG-monomethyl L-arginine, and endothelin-1.

PubMed

Lawson, D L; Haught, W H; Mehta, P; Mehta, J L

1996-09-01

Development of vascular tolerance to nitroglycerin (NTG) has been attributed to sulfhydryl (SH) depletion, guanylate cyclase desensitization, or both. Controversy regarding the precise contribution of these mechanisms may be due to variations in experimental design. To examine further the biochemical basis of NTG tolerance, norepinephrine (NE)-precontracted rat aortic rings were exposed to NTG (10(-5)M), which resulted in 84 +/- 6% relaxation. Other rings were first superfused with NTG (10(-6)M) and then contracted with NE. These rings showed a marked tolerance to the vasorelaxant effects of NTG (maximal relaxation 20 +/- 5%, n = 15, p < 0.001 vs. control rings). Similar tolerance to NTG was observed when the vascular rings were first superfused with acetylcholine (ACh 10(-6)M), indicating cross-tolerance between ACh and NTG. Treatment of NTG-tolerant rings with N-acetylcysteine (NAC) (10(-5)M) did not restore vascular smooth muscle (VSM) relaxation in response to NTG (maximal relaxation 23 +/- 5%, n = 8), suggesting that SH depletion may not be the basis of NTG tolerance in these experiments. Parallel sets of NTG-tolerant aortic rings were contracted with endothelin-1 (ET-1, n = 5) or the endothelium-derived relaxing factor (EDRF) synthase inhibitor NG-monomethyl L-arginine (L-NMMA, 10(-4)M, n = 8). In both ET-1- and L-NMMA-contracted rings, vascular relaxation in response to NTG was preserved (80 +/- 6 and 88 +/- 8% relaxation, respectively). Measurement of cyclic GMP in aortic rings showed marked accumulation on initial exposure of tissues to NTG (310 +/- 10 fmol/mg), whereas the NTG-tolerant rings showed much less cyclic GMP accumulation (48 +/- 29 fmol/mg). Rings contracted with L-NMMA or ET-1, but not NE, accumulated cyclic GMP when exposed to NTG (280 +/- 20 fmol/mg). These data indicate that NTG tolerance develops on exposure of vascular rings superfused with NTG or ACh and is probably not related to tissue SH depletion. Contraction of NTG-tolerant rings with ET-1 or L-NMMA restores NTG-mediated relaxation.

Non-ST-segment elevation syndromes. Pharmacologic management, conservative versus early invasive approach.

PubMed

Santiago, Patrick; Tadros, Peter

2002-07-01

Many advances have been made in the treatment of acute coronary syndromes. Patients with intermediate-risk or high-risk features should receive treatment with the newer pharmacologic agents--enoxaparin, statins and, in selected cases, clopidogrel--in addition to established standard therapies (i.e., aspirin, beta-blockers, nitroglycerin, and oxygen). Use of GpIIb-IIIa inhibitors should also be strongly considered, especially in an early invasive approach. However, there is no substitute for a good physician who has the big picture and knows the individual patient in totality. This physician can best judge the dangers of the patient's acute cardiac condition against the comorbidities that may be exacerbated by revascularization procedures. The ability to weigh the risks of the patient's acute coronary syndrome against the risks of an aggressive invasive approach ultimately provides the best care for each patient.

Expanding Biosensing Abilities through Computer-Aided Design of Metabolic Pathways.

PubMed

Libis, Vincent; Delépine, Baudoin; Faulon, Jean-Loup

2016-10-21

Detection of chemical signals is critical for cells in nature as well as in synthetic biology, where they serve as inputs for designer circuits. Important progress has been made in the design of signal processing circuits triggering complex biological behaviors, but the range of small molecules recognized by sensors as inputs is limited. The ability to detect new molecules will increase the number of synthetic biology applications, but direct engineering of tailor-made sensors takes time. Here we describe a way to immediately expand the range of biologically detectable molecules by systematically designing metabolic pathways that transform nondetectable molecules into molecules for which sensors already exist. We leveraged computer-aided design to predict such sensing-enabling metabolic pathways, and we built several new whole-cell biosensors for molecules such as cocaine, parathion, hippuric acid, and nitroglycerin.

Osler on migraine.

PubMed

Boes, Christopher J

2015-03-01

William Osler's 1892 textbook The Principles and Practice of Medicine became the dominant medical text in the English-speaking world. Osler was labeled a therapeutic nihilist by some. The topic of migraine, including treatment, was succinctly covered in his text. The objectives of this study were to review Osler's thoughts on migraine, and outline his therapeutic recommendations. Preventively Osler mentioned bromides, iron, arsenic, nitroglycerin, and cannabis. Acutely he recommended coffee, chloroform, cannabis, antipyrin, antifebrin, phenacetin, caffeine citrate, nux vomica, or ergot. He thought cannabis was the most satisfactory remedy. Osler was not a therapeutic nihilist when it came to migraine, and his treatment recommendations were similar to other writers of his time. Osler did not draw upon his personal experience to contribute new knowledge about migraine. Regardless, given the popularity and clarity of his text, Osler's well-summarized migraine chapter had a great influence on practicing physicians.

Nitrates for the prevention of cardiac morbidity and mortality in patients undergoing non-cardiac surgery.

PubMed

Zhao, Na; Xu, Jin; Singh, Balwinder; Yu, Xuerong; Wu, Taixiang; Huang, Yuguang

2016-08-04

Cardiac complications are not uncommon in patients undergoing non-cardiac surgery, especially in patients with coronary artery disease (CAD) or at high risk of CAD. Perioperative cardiac complications can lead to mortality and morbidity, as well as higher costs for patient care. Nitrates, which are among the most commonly used cardiovascular drugs, perform the function of decreasing cardiac preload while improving cardiac blood perfusion. Sometimes, nitrates are administered to patients undergoing non-cardiac surgery to reduce the incidence of cardiac complications, especially for patients with CAD. However, their effects on patients' relevant outcomes remain controversial. • To assess effects of nitrates as compared with other interventions or placebo in reducing cardiac risk (such as death caused by cardiac factors, angina pectoris, acute myocardial infarction, acute heart failure and cardiac arrhythmia) in patients undergoing non-cardiac surgery.• To identify the influence of different routes and dosages of nitrates on patient outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Chinese BioMedical Database until June 2014. We also searched relevant conference abstracts of important anaesthesiology or cardiology scientific meetings, the database of ongoing trials and Google Scholar.We reran the search in January 2016. We added three potential new studies of interest to the list of 'Studies awaiting classification' and will incorporate them into our formal review findings for the review update. We included randomized controlled trials (RCTs) comparing nitrates versus no treatment, placebo or other pharmacological interventions in participants (15 years of age and older) undergoing non-cardiac surgery under any type of anaesthesia. We used standard methodological procedures as expected by Cochrane. Two review authors selected trials, extracted data from included studies and assessed risk of bias. We resolved differences by discussion and, when necessary, sought help and suggestions from a third review author. We used a random-effects model for data analysis. We included 27 randomized controlled trials (RCTs) (8244 participants analysed). Investigators reported 12 different comparisons of three different nitrates (nitroglycerin, isosorbide dinitrate and nicorandil) versus no treatment, placebo or other pharmacological interventions. All participants were older than 15 years of age. More than half of the trials used general anaesthesia. Surgical procedures in most trials were at low to moderate risk for perioperative cardiac complications. Only two comparisons including three studies reported the primary outcome - all-cause mortality up to 30 days post operation. Researchers reported other morbidity outcomes and adverse events in a variable and heterogeneous way, resulting in limited available data for inclusion in the meta-analysis. We determined that the overall methodological quality of included studies was fair to low, in accordance with risk of bias in most domains.In summary, we found no difference in the primary outcome - all-cause mortality up to 30 days post operation - when nitroglycerin was compared with no treatment (one study, 60 participants, 0/30 vs 1/30; (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.01 to 7.87, very low-quality evidence based on GRADE criteria) or with placebo (two studies, 89 participants, 1/45 vs 0/44; RR 2.81, 95% CI 0.12 to 63.83, very low-quality evidence). Regarding our secondary outcomes, we noted no statistically significant differences in angina pectoris, acute myocardial infarction, acute heart failure, cardiac arrhythmia or cardiac arrest in any comparisons. In comparisons versus nitroglycerin, although more events of cardiac ischaemia were observed in participants receiving no treatment or placebo, we found no statistically significant differences in any comparisons, except the comparison of nicorandil versus placebo. One study revealed a potential dose-dependent protective effect of nicorandil for cardiac ischaemia.Adverse events were reported in a heterogeneous way among the comparisons. In general, more participants treated with nitrates had hypotension, tachycardia and headache, but investigators reported no statistically significant differences between groups in any comparisons. This systematic review suggests that nitroglycerin or isosorbide dinitrate is not associated with improvement in mortality and cardiac complications among patients undergoing non-cardiac surgery. Limited evidence suggests that nicorandil may reduce the risk of cardiac ischaemia in participants undergoing non-cardiac surgery. Additional studies are needed to consolidate the evidence.However, the data included in many of the analyses in this review are sparse - that is, adequate data are few - resulting in very low power to detect differences between nitrates and comparators. Thus, a more objective conclusion would state that available evidence is insufficient to show whether nitrates are associated with improvement in mortality and cardiac complications among patients undergoing non-cardiac surgery.Over the past decade, no high-quality studies have focused on association of cardiac mortality and morbidity with use of nitrates during non-cardiac surgery. This review underlines the need for well-designed trials in this field.

Severe portopulmonary hypertension in congenital hepatic fibrosis.

PubMed

Hsu, Chen-Ming; Chiu, Cheng-Tang; Lien, Jau-Min; Ng, Kwai-Fong

2003-03-01

Portopulmonary hypertension is a rare complication of portal hypertension. Although epoprostenol infusion, nitric oxide inhalation, isosorbide-5-mononitrate, nitroglycerin, and calcium channel blockers may reduce pulmonary artery pressure in patients with portopulmonary hypertension, the prognosis remains poor. We present a case of congenital hepatic fibrosis associated with pulmonary hypertension. A 42-year-old man with congenital hepatic fibrosis visited our hospital with syncope. The man had suffered from breathlessness on exertion for 2 weeks before the episode of syncope. He also had a history of portal hypertension with documented gastric cardiac varices at the age of 28 years. Despite undergoing intensive care, the patient died 1 week after admission owing to severe right-sided heart failure. Autopsy revealed dilatation of the right atrium and right ventricle grossly and plexogenic pulmonary arteriopathy microscopically. Accurate diagnosis of portopulmonary hypertension requires awareness of the disease and a high index of suspicion when examining patients with portal hypertension and dyspnea.

Photoactive energetic materials

DOEpatents

Chavez, David E.; Hanson, Susan Kloek; Scharff, Robert Jason; Veauthier, Jacqueline Marie; Myers, Thomas Winfield

2018-02-27

Energetic materials that are photoactive or believed to be photoactive may include a conventional explosive (e.g. PETN, nitroglycerine) derivatized with an energetic UV-absorbing and/or VIS-absorbing chromophore such as 1,2,4,5-tetrazine or 1,3,5-triazine. Absorption of laser light having a suitably chosen wavelength may result in photodissociation, decomposition, and explosive release of energy. These materials may be used as ligands to form complexes. Coordination compounds include such complexes with counterions. Some having the formula M(L).sub.n.sup.2+ were synthesized, wherein M is a transition metal and L is a ligand and n is 2 or 3. These may be photoactive upon exposure to a laser light beam having an appropriate wavelength of UV light, near-IR and/or visible light. Photoactive materials also include coordination compounds bearing non-energetic ligands; in this case, the counterion may be an oxidant such as perchlorate.

Alterations in the trapezius muscle in young patients with migraine--a pilot case series with MRI.

PubMed

Landgraf, M N; Ertl-Wagner, B; Koerte, I K; Thienel, J; Langhagen, T; Straube, A; von Kries, R; Reilich, P; Pomschar, A; Heinen, F

2015-05-01

Migraine is frequent in young adults and adolescents and often associated with neck muscle tension and pain. Common pathophysiological pathways, such as reciprocal cervico-trigeminal activation, are assumed. Tense areas within the neck muscles can be clinically observed many patients with migraine. The aim of this pilot case study was to visualize these tense areas via magnet resonance imaging (MRI). Three young patients with migraine were examined by an experienced investigator. In all three patients tense areas in the trapezius muscles were palpated. These areas were marked by nitroglycerin capsules on the adjacent skin surface. The MRI showed focal signal alterations at the marked locations within the trapezius muscles. Visualization of palpable tense areas by MRI may be usefully applied in the future to help elucidate the underlying pathophysiological processes of migraine. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Aminoethyl nitrate – the novel super nitrate?

PubMed Central

Bauersachs, Johann

2009-01-01

Long-term use of most organic nitrates is limited by development of tolerance, induction of oxidative stress and endothelial dysfunction. In this issue of the BJP, Schuhmacher et al. characterized a novel class of organic nitrates with amino moieties (aminoalkyl nitrates). Aminoethyl nitrate was identified as a novel organic mononitrate with high potency but devoid of induction of mitochondrial oxidative stress. Cross-tolerance to nitroglycerin or the endothelium-dependent agonist acetylcholine after in vivo treatment was not observed. Like all nitrates, aminoethyl nitrate induced vasorelaxation by activation of soluble guanylate cyclase. Thus, in contrast to the prevailing view, high potency in an organic nitrate is not necessarily accompanied by induction of oxidative stress or endothelial dysfunction. This work from Daiber's group is an important step forward in the understanding of nitrate bioactivation, tolerance phenomena and towards the development of better organic nitrates for clinical use. PMID:19732062

Rockets, radiosensitizers, and RRx-001: an origin story part I.

PubMed

Oronsky, Bryan; Scicinski, Jan; Ning, Shoucheng; Peehl, Donna; Oronsky, Arnold; Cabrales, Pedro; Bednarski, Mark; Knox, Susan

2016-03-01

From Adam and Eve, to Darwinism, origin stories attempt to fill in the blanks, connect the dots, and define the turning points that are fundamental to subsequent developments. The purpose of this review is to present the origin story of a one-of-a-kind anticancer agent, RRx-001, which emerged from the aerospace industry as a putative radiosensitizer; not since the dynamite-to-dilator transformation of nitroglycerin in 1878 or the post-World War II explosive-to-elixir conversion of hydralazine, an ingredient in rocket fuel, to an antihypertensive, an antidepressant and an antituberculant, has energetic chemistry been harnessed for therapeutic purposes. This is Part 1 of the radiosensitization story; Parts 2 and 3, which detail the crossover activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews.

Treatment of essential and parkinsonian tremor with nipradilol.

PubMed

Yoshii, F; Shinohara, Y; Takeoka, T; Kitagawa, Y; Akiyama, K; Yazaki, K

1996-11-01

Nipradilol is a new type of beta-blocker which possesses nitroglycerin-like vasodilating action in addition to beta-blocking action. We investigated the efficacy and safety of nipradilol for treating tremor in 20 patients with essential tremor (ET group) and 20 patients with Parkinson's disease (PD group). All patients received nipradilol (6 mg per day) for more than 8 weeks. Improvement of tremor appeared within 2 or 4 weeks after the start of nipradilol therapy, and the efficacy rate, defined as "moderately effective" or over, was 42.5% in all 40 patients, while that defined as "slightly effective" or over was 87.5%. The efficacy rate tended to be higher in the ET group compared with the PD group. Mean blood pressure was significantly decreased from the 4th week after the start of treatment and heart rate was significantly reduced from the 2nd week of treatment. Laboratory examination showed no significant changes.

Use of nitrates in ischemic heart disease.

PubMed

Giuseppe, Cocco; Paul, Jerie; Hans-Ulrich, Iselin

2015-01-01

Short-acting nitrates are beneficial in acute myocardial ischemia. However, many unresolved questions remain about the use of long-acting nitrates in stable ischemic heart disease. The use of long-acting nitrates is weakened by the development of endothelial dysfunction and tolerance. Also, we currently ignore whether lower doses of transdermal nitroglycerin would be better than those presently used. Multivariate analysis data from large nonrandomized studies suggested that long-acting nitrates increase the incidence of acute coronary syndromes, while data from another multivariate study indicate that they have positive effects. Because of methodological differences and open questions, the two studies cannot be compared. A study in Japanese patients with vasospastic angina has shown that, when compared with calcium antagonists, long-acting nitrates do not improve long-term prognosis and that the risk for cardiac adverse events increases with the combined therapy. We have many unanswered questions.

Running injuries - changing trends and demographics.

PubMed

Fields, Karl B

2011-01-01

Running injuries are common. Recently the demographic has changed, in that most runners in road races are older and injuries now include those more common in master runners. In particular, Achilles/calf injuries, iliotibial band injury, meniscus injury, and muscle injuries to the hamstrings and quadriceps represent higher percentages of the overall injury mix in recent epidemiologic studies compared with earlier ones. Evidence suggests that running mileage and previous injury are important predictors of running injury. Evidence-based research now helps guide the treatment of iliotibial band, patellofemoral syndrome, and Achilles tendinopathy. The use of topical nitroglycerin in tendinopathy and orthotics for the treatment of patellofemoral syndrome has moderate to strong evidence. Thus, more current knowledge about the changing demographics of runners and the application of research to guide treatment and, eventually, prevent running injury offers hope that clinicians can help reduce the high morbidity associated with long-distance running.

[Nicergoline-induced Prinzmetal angina. "Heartache" instead of headache].

PubMed

Tomcsányi, János; Vecsey, Tibor; Tátrai, Tihamér

2004-01-04

A 56 year old woman was admitted to our hospital with crescendo chest pain in the last ten days. Her past history included hypertension treated by 100 mg metoprolol for more than ten years and right carotid endarterectomy. She complained headache and a treatment of 20 mg nicergoline (ergoline derivate) daily was started. Her chest pains started always one hour after the nicergoline intake. The chest pain was accompanied by breathing difficulties and sweating of 5 min duration at first but the next days it lasted longer and longer. Next morning following her admission, one hour after the nicergoline administration she had severe chest pain again. The ECG showed ST-segment elevation in inferior leads resolved after nitroglycerin administration. The angiogram revealed normal coronary artery. Nicergoline was stopped. The patient was treated with felodipine and remains free of symptoms. Nicergoline was good for head but worse for heart in this case.

ISMP Adverse Drug Reactions: Pregabalin-Induced Stuttering Nitroglycerine-Induced Bradycardia Progressing to Asystole Minocycline-Induced DRESS Leading to Liver Transplantation and Type 1 Diabetes Increased Risk of Vertebral Fractures in Women Receiving Thiazide or Loop Diuretics Gambling Disorder and Impulse Control Disorder with Aripiprazole.

PubMed

Mancano, Michael A

2017-04-01

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Lead-Free Double-Base Propellant for the 2.75 Inch Rocket Motor

NASA Technical Reports Server (NTRS)

Magill, B. T.; Nauflett, G. W.; Furrow, K. W.

2000-01-01

The current MK 66 2.75 inch Rocket Motor double-base propellant contains the lead-based ballistic modifier LC-12-15 to achieve the desired plateau and mesa burning rate characteristics. The use of lead compounds poses a concern for the environment and for personal safety due to the metal's toxic nature when introduced into the atmosphere by propellant manufacture, rocket motor firing, and disposal. Copper beta-resorcylate (copper 2,4-di-hydroxy-benzoate) was successfully used in propellant as a simple modifier in the mid 1970's. This and other compounds have also been mixed with lead salts to obtain more beneficial ballistic results. Synthesized complexes of lead and copper compounds soon replaced the mixtures. The complexes incorporate the lead, copper lack of organic liquids, which allows for easier propellant processing. About ten years ago, the Indian Head Division, Naval Surface Warfare Center (NSWC), initiated an effort to develop a lead-free propellant for use in missile systems. Several lead-free propellant candidate formulations were developed. About five years ago, NSWC, in conjunction with Alliant Techsystems, Radford Army Ammunition Plant, continued ballistic modifier investigations. A four component ballistic modifier system without lead for double-base propellants that provide adequate plateau and mesa burn rate characteristics was developed and patented. The ballistic modifier's system contains bismuth subsalicylate, 1.5 percent; copper salicylate, 1.0 percent, copper stannate, 0.77 percent; and carbon black, 0.1 percent. Action time and impulse data obtained through multiple static firings indicate that the new lead-free double-base propellant, while not a match for NOSIH-AA-2, will be a very suitable replacement in the 2.75 inch Rocket Motor. Accelerated aging of the double-base propellant containing the lead-free ballistic modifier showed that it had a much higher rate of stabilizer depletion than the AA-2. A comprehensive study showed that an increased rate of stabilizer depletion occurred in propellants containing monobasic copper salicylate. The study also showed that propellants containing a mixture of bismuth subsalicylate and copper salicylate, had only about one-half the stabilizer depletion rate than those with copper salicylate alone. The copper salicylate catalyzes the decomposition of nitroglycerin, which triggers a chain of events leading to the increased rate of stabilizer depletion. A program has been initiated to coat the ballistic modifier, thus isolating it from the nitroglycerin.

[18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches.

PubMed

de Jong, Evelyn E C; van Elmpt, Wouter; Leijenaar, Ralph T H; Hoekstra, Otto S; Groen, Harry J M; Smit, Egbert F; Boellaard, Ronald; van der Noort, Vincent; Troost, Esther G C; Lambin, Philippe; Dingemans, Anne-Marie C

2017-01-01

Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival. A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG. A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively). The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment showed more tumor responders than CT-based response assessment (part of the [18F]FDG PET/CT); this was not correlated to survival. This might be due to timing of the [18F]FDG PET shortly after the bevacizumab infusion.

A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†.

PubMed

Dingemans, A-M C; Groen, H J M; Herder, G J M; Stigt, J A; Smit, E F; Bahce, I; Burgers, J A; van den Borne, B E E M; Biesma, B; Vincent, A; van der Noort, V; Aerts, J G

2015-11-01

Nitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cisplatin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. In this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)-paclitaxel (200 mg/m(2))-bevacizumab 15 mg/kg on day 1 every 3 weeks with or without NTG patches 15 mg (day -2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at α = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. Between 1 January 2011 and 1 January 2013, a total of 223 patients were randomized; 112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6-7.3) and 5.1 months (4.2-5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96-1.67). Overall survival (OS) was 11.6 months (8.8-13.6) in control arm and 9.4 months (7.8-11.3) in experimental arm, HR 1.02 (95% CI 0.71-1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). Adding NTG to first-line carboplatin-paclitaxel-bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prehospital Nitroglycerin in Tachycardic Chest Pain Patients: A Risk for Hypotension or Not?

PubMed

Proulx, Marie-Hélène; de Montigny, Luc; Ross, Dave; Vacon, Charlene; Juste, Louis Enock; Segal, Eli

2017-01-01

The American Heart Association guidelines (AHA) guidelines list tachycardia as a contraindication for the administration of nitroglycerin (NTG), despite limited evidence of adverse events. We sought to determine whether NTG administered for chest pain was a predictor of hypotension (systolic blood pressure <90 mmHg) in patients with tachycardia, compared to patients without tachycardia (50≥ heart rate ≤100). We performed a retrospective cohort study using patient care reports completed by basic life support (BLS) providers in a large urban Canadian EMS system for the period 2010-2012. We used logistic regression to test the association between post-NTG hypotension and tachycardia, independent of pre-NTG blood pressure, age, sex, and comorbidities. Using identical models, we tested four secondary outcomes (drop in blood pressure, reduced consciousness, bradycardia, and cardiac arrest). The cohort included 10,308 patients who were administered NTG by BLS in the prehospital setting; 2,057 (20%) of patients were tachycardic before NTG administration. Hypotension occurred in 320 of all patients (3.1%): 239 without tachycardia (2.9%) and 81 with tachycardia (3.9%). Compared to non-tachycardic patients, tachycardic patients showed increased adjusted odds of hypotension (AOR: 1.60; 95% CI: 1.23-2.08) or of a drop in blood pressure of 30mm Hg or greater (AOR: 1.11; CI: 1.00-1.24). Tachycardia was associated with decreased odds of bradycardia (OR: 0.33; CI: 0.17-0.64). We did not find a significant association between tachycardia and either post-NTG reduced level of consciousness or cardiac arrest. We did find a strong, significant association between pre-NTG blood pressure and post-NTG hypotension (AOR for units of 10mmHg: 0.64; CI: 0.61-0.69). Hypotension following prehospital administration of NTG was infrequent in patients with chest pain. However, while the absolute risk of NTG-induced hypotension was low, patients with pre-NTG tachycardia had a significant increase in the relative risk of hypotension. In addition, hypotension occurred most frequently in patients presenting with a lower pre-NTG blood pressure, which may prove to be a more discriminating basis for future guidelines. EMS medical directors should review BLS chest pain protocols to weigh the benefits of NTG administration against its risks.

Clevidipine compared with nitroglycerin for blood pressure control in coronary artery bypass grafting: a randomized double-blind study.

PubMed

Merry, Alan F; Avery, Edwin G; Nussmeier, Nancy A; Playford, Hugh R; Warman, Guy R; Wang, Yamei; Sladen, Robert N

2014-05-01

We tested the hypothesis that clevidipine, a rapidly acting dihydropyridine calcium channel blocker, is not inferior to nitroglycerin (NTG) in controlling blood pressure before cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG). In this double-blind study from October 4, 2003 to April 26, 2004, 100 patients undergoing CABG with CPB were randomized at four centres to receive intravenous infusions of clevidipine (0.2-8 μg·kg(-1)·min(-1)) or NTG (0.4 μg·kg(-1)·min(-1) to a clinician-determined maximum dose rate) from induction of anesthesia through 12 hr postoperatively. The study drug was titrated in the pre-CPB period with the aim of maintaining mean arterial pressure (MAP) within ± 5 mmHg of a clinician-predetermined target. The primary endpoint was the area under the curve (AUC) for the total time each patient's MAP was outside the target range from drug initiation to the start of CPB, normalized per hour (AUCMAP-D). The predefined non-inferiority criterion for the primary endpoint was a 95% confidence interval (CI) upper limit no greater than 1.50 for the geometric means ratio between clevidipine and NTG. Total mean [standard deviation (SD)] dose pre-bypass was 4.5 (4.7) mg for clevidipine and 6.9 (5.4) mg for NTG (P < 0.05). The geometric mean AUCMAP-D for clevidipine was 283 mmHg·min·hr(-1) (n = 45) and for NTG was 292 mmHg·min·hr(-1) (n = 48); the geometric means ratio was 0.97 (95% CI 0.74 to 1.27). The geometric mean AUCMAP-D during aortic cannulation was 357.7 mmHg·min·hr(-1) for clevidipine compared with 190.5 mmHg·min·hr(-1) for NTG. Mean (SD) heart rate with clevidipine was 76.0 (13.8) beats·min(-1) compared with 81.5 (14.4) beats·min(-1) for NTG. There were no clinically important differences between groups in adverse events. During CABG, clevidipine was not inferior to NTG for blood pressure control pre-bypass.

Improved endothelial function and lipid profile compensate for impaired hemostatic and inflammatory status in iatrogenic chronic subclinical hyperthyroidism of thyroid cancer patients on L-t4 therapy.

PubMed

Gazdag, A; Nagy, E V; Burman, K D; Paragh, G; Jenei, Z

2010-06-01

We aimed to compare the changes of endothelial function and haemostatic, inflammatory and metabolic parameters of short-term iatrogenic hypothyroidism to the characteristics of subclinical hyperthyroidism in patients with differentiated thyroid cancer. Twenty four women (mean age 42.4+/-8.1 years) had undergone total thyroidectomy and radioiodine ablation in treatment for differentiated thyroid cancer. We measured serum thyroglobulin, thyroid function, plasma levels of lipid parameters, homocystine, C-reactive protein, fibrinogen, von Willebrandt factor activity (vWF), nitric oxide, as well as flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation of the brachial artery during iatrogenic hypothyroidism (TSH 89.82+/-29.36 mU/L) and again in the same patients during subclinical hyperthyroidism secondary to exogenous levothyroxine administration (TSH 0.24+/-0.11 mU/L). In hypothyroidism, FMD was markedly lower than in subclinical hyperthyroidism (6.79+/-4.44 vs. 14.37+/-8.33%, p<0.005). Total cholesterol (7.34+/-1.23 vs. 4.75+/-1.14 mmol/L, p<0.001), LDL-cholesterol (4.55+/-1.10 vs. 2.70+/-0.89 mmol/L, p<0.005) and homocystine (12.95+/-4.49 vs. 9.62+/-2.29 micromol/L, p<0.005) were significantly higher in hypothyroidism. There was no difference in nitroglycerin-mediated vasodilatation, blood pressure, serum triglyceride and HDL-cholesterol levels according to thyroid function. Fibrinogen (3.23+/-0.50 vs. 4.01+/-0.84 g/L, p<0.005), vWF (90.09+/-25.92 vs.130.63+/-29.97%, p<0.001), C-reactive protein (4.39+/-5.16 vs. 5.55+/-5.15 mg/L, p<0.001) and plasma nitric oxide (24.56+/-6.71 vs. 32.34+/-7.0 micromol/L, <0.005) values were significantly lower in hypothyroidism. FMD correlated in a positive manner with fibrinogen, vWF and nitrogen oxide. Chronic subclinical hyperthyroidism was associated with improved endothelial function and lipid profile, while haemostatic and inflammatory parameters were impaired. The two opposite mechanisms may well compensate for each other at the level of the vessel wall. (c) J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart, New York.

Abnormal myocardial fluid retention as an early manifestation of ischemic injury.

PubMed Central

Willerson, J. T.; Scales, F.; Mukherjee, A.; Platt, M.; Templeton, G. H.; Fink, G. S.; Buja, L. M.

1977-01-01

Fifty-seven isolated, blood perfused, continuously weighed canine hearts have been utilized to study the development of abnormal myocardial fluid retention during early myocardial ischemic injury. Inflatable balloon catheters were positioned around the left anterior descending coronary arteries (LAD) of 54 hearts or the proximal left circumflex coronary arteries of three hearts for study of the following intervals of coronary occlusion: a) 10 minutes followed by 20 minutes of reflow, b) 40 minutes followed by either no reflow or by 20 minutes of reflow, and c) 60 minutes without reflow. After 60 minutes of fixed coronary occlusion, histologic and ultrastructural examination revealed mild swelling of many ischemic cardiac muscle cells in the absence of interstitial edema, cardiac weight gain, and obvious structural defects in cell membrane integrity. After 40 minutes of coronary occlusion and 20 minutes of reflow, significant cardiac weight gain occurred in association with characteristic alterations in the ischemic region, including widespread interstitial edema and focal vascular congestion and hemorrhage and swelling of cardiac muscle cells. Focal structural defects in cell membrane integrity were also noted. The development of abnormal myocardial fluid retention after 40 minutes of LAD occlusion occurred in association with a significant reduction in sodium-potassium-ATPase activity in the ischemic area, but with no significant alteration in either creatine phosphokinase or citrate synthase activity in the same region. Despite the abnormal myocardial fluid retention in these hearts, it was possible pharmacologically to vasodilate coronary vessels with adenosine and nitroglycerin infusion to maintain a consistently high coronary flow following release of the coronary occlusion after 40 minutes and to even exceed initial hyperemic flow values following release of the occlusion when adenosine and nitroglycerin infusion was delayed until 15 minutes after reflow. Thus, the data indicate that impaired cell volume regulation and interstitial fluid accumulation and focal structural defects in cell membrane integrity are early manifestations of ischemic injury followed by reflow, but fail to establish a major role for the abnormal fluid retention in altering coronary blood flow prior to the development of extensive myocardial necrosis. In contrast, fixed coronary occlusion for 60 minutes results in mild intracellular swelling but no significant interstitial edema and no obvious structural defects in cell membrane integrity. Images Figure 1 Figure 5 Figure 6 Figure 2 Figure 3 Figure 4 PMID:139829

Times and locations of explosions; U.S. Geological Survey 1962 field season

USGS Publications Warehouse

Roller, John C.

1962-01-01

The U.S. Geological Survey detonated 86 large charges of chemical explosives in the western United States from 6 June to 9 August 1962, in a study of crustal structure in the western United States. This Technical Letter consists of two tables containing information about these explosions. Table I gives a brief geographical description of the shotpoints, and Table II gives the date, time, location, charge size, surface elevation, and some general information about the shots. In the Remarks column (Table II), the configuration and depth of most of the charges are given. This part of the table is not complete, as some of this information has not yet been compiled. Three types of explosives were used in the program. These were: Nitramon WW, a carbo-nitrate blasting agent; Composition B, a mixture of RDX and TNT; and Tovex-Gel, a non-nitroglycerin blasting slurry. The loading, firing, and surveying was done by United ElectroDynamics, Inc., of Pasadena, California. The timing was done by the U.S. Geological Survey.

A Study of a QCM Sensor Based on TiO₂ Nanostructures for the Detection of NO₂ and Explosives Vapours in Air.

PubMed

Procek, Marcin; Stolarczyk, Agnieszka; Pustelny, Tadeusz; Maciak, Erwin

2015-04-22

The paper deals with investigations concerning the construction of sensors based on a quartz crystal microbalance (QCM) containing a TiO2 nanostructures sensor layer. A chemical method of synthesizing these nanostructures is presented. The prepared prototype of the QCM sensing system, as well as the results of tests for detecting low NO2 concentrations in an atmosphere of synthetic air have been described. The constructed NO2 sensors operate at room temperature, which is a great advantage, because resistance sensors based on wide gap semiconductors often require much higher operation temperatures, sometimes as high as 500 °C. The sensors constructed by the authors can be used, among other applications, in medical and chemical diagnostics, and also for the purpose of detecting explosive vapours. Reactions of the sensor to nitroglycerine vapours are presented as an example of its application. The influence of humidity on the operation of the sensor was studied.

Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine

PubMed Central

Greco, Rosaria; Siani, Francesca; Demartini, Chiara; Zanaboni, Annamaria; Nappi, Giuseppe; Davinelli, Sergio; Scapagnini, Giovanni; Tassorelli, Cristina

2016-01-01

Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNF-alpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine. PMID:27027895

Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine.

PubMed

Greco, Rosaria; Siani, Francesca; Demartini, Chiara; Zanaboni, Annamaria; Nappi, Giuseppe; Davinelli, Sergio; Scapagnini, Giovanni; Tassorelli, Cristina

2016-01-01

Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.

Effect of Nitrooxy Compounds with Different Molecular Structures on the Rumen Methanogenesis, Metabolic Profile, and Methanogenic Community.

PubMed

Jin, Wei; Meng, Zhenxiang; Wang, Jing; Cheng, Yanfen; Zhu, Weiyun

2017-08-01

Rumen in vitro fermentation was used to evaluate the capacity of nitrooxy compounds to mitigate rumen methane production. The following three nitrooxy compounds, each with different molecular structures, were evaluated: 2,2-dimethyl-3-(nitrooxy) propanoic (DNP), N-[2-(Nitrooxy)ethyl]-3-pyridinecarboxamide (NPD), and nitroglycerin (NG). All three compounds substantially decreased the total gas production, methane production, and the acetate:propionate ratio, while increasing hydrogen production. The growth of methanogens was specifically inhibited by all three compounds, without affecting the abundance of bacteria, anaerobic fungi, or protozoa. However, inhibition of methanogenesis required a much higher dose of DNP when compared to NPD or NG. Further investigations were conducted on NG to determine its effects on the methanogenic community. NG reduced the relative abundance of Methanomassiliicoccales, while increasing the relative abundance of Methanobrevibacter and Methanosphaera. Overall, the results suggested that all three of these nitrooxy compounds could specifically inhibit rumen methanogenesis, but NPD and NG were much more efficient than DNP at rumen methane mitigation.

Effect of nipradilol, a beta-adrenergic blocker with vasodilating activity, on oxotremorine-induced tremor in mice.

PubMed

Iwata, S; Nomoto, M; Fukuda, T

1996-10-01

The effect of nipradilol, a nonselective beta-adrenergic receptor blocker with nitroglycerin-like vasodilating activity, on oxotremorine-induced tremor was studied in mice. General tremor in mice was elicited by 0.5 mg/kg oxotremorine. The tremor was quantified using a capacitance transducer, then analyzed by a signal processor. The strength of the tremor was expressed in "points". The point values of the tremor (mean +/- SE) in control mice for 5 mg/kg (+/-)-propranolol, 2.5 mg/kg arotinolol, 0.5 mg/kg nipradilol, 1.0 mg/kg nipradilol and 2.5 mg/kg nipradilol were 87 +/- 16, 42 +/- 6, 38 +/- 6, 99 +/- 28, 28 +/- 6 and 31 +/- 7, respectively. The strength of the tremor was reduced by all beta-blockers. Although 1.0 mg/kg nipradilol significantly reduced the tremor, further inhibition of the tremor was not obtained with dosages up to 2.5 mg/kg of the drug. In conclusion, nipradilol was effective for suppressing oxotremorine-induced tremor, as were other beta-blockers.

Trace explosives sensor testbed (TESTbed)

NASA Astrophysics Data System (ADS)

Collins, Greg E.; Malito, Michael P.; Tamanaha, Cy R.; Hammond, Mark H.; Giordano, Braden C.; Lubrano, Adam L.; Field, Christopher R.; Rogers, Duane A.; Jeffries, Russell A.; Colton, Richard J.; Rose-Pehrsson, Susan L.

2017-03-01

A novel vapor delivery testbed, referred to as the Trace Explosives Sensor Testbed, or TESTbed, is demonstrated that is amenable to both high- and low-volatility explosives vapors including nitromethane, nitroglycerine, ethylene glycol dinitrate, triacetone triperoxide, 2,4,6-trinitrotoluene, pentaerythritol tetranitrate, and hexahydro-1,3,5-trinitro-1,3,5-triazine. The TESTbed incorporates a six-port dual-line manifold system allowing for rapid actuation between a dedicated clean air source and a trace explosives vapor source. Explosives and explosives-related vapors can be sourced through a number of means including gas cylinders, permeation tube ovens, dynamic headspace chambers, and a Pneumatically Modulated Liquid Delivery System coupled to a perfluoroalkoxy total-consumption microflow nebulizer. Key features of the TESTbed include continuous and pulseless control of trace vapor concentrations with wide dynamic range of concentration generation, six sampling ports with reproducible vapor profile outputs, limited low-volatility explosives adsorption to the manifold surface, temperature and humidity control of the vapor stream, and a graphical user interface for system operation and testing protocol implementation.

A Study of a QCM Sensor Based on TiO2 Nanostructures for the Detection of NO2 and Explosives Vapours in Air

PubMed Central

Procek, Marcin; Stolarczyk, Agnieszka; Pustelny, Tadeusz; Maciak, Erwin

2015-01-01

The paper deals with investigations concerning the construction of sensors based on a quartz crystal microbalance (QCM) containing a TiO2 nanostructures sensor layer. A chemical method of synthesizing these nanostructures is presented. The prepared prototype of the QCM sensing system, as well as the results of tests for detecting low NO2 concentrations in an atmosphere of synthetic air have been described. The constructed NO2 sensors operate at room temperature, which is a great advantage, because resistance sensors based on wide gap semiconductors often require much higher operation temperatures, sometimes as high as 500 °C. The sensors constructed by the authors can be used, among other applications, in medical and chemical diagnostics, and also for the purpose of detecting explosive vapours. Reactions of the sensor to nitroglycerine vapours are presented as an example of its application. The influence of humidity on the operation of the sensor was studied. PMID:25912352

Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

PubMed

Schmidl, D; Polska, E; Kiss, B; Sacu, S; Garhofer, G; Schmetterer, L

2010-01-01

Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.

Effects of isradipine and other calcium antagonists on arteriovenous-shunt flow in anesthetized rabbits and cats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hof, R.P.

The effects of vasodilators on arteriovenous (AV)-shunt flow was investigated in anesthetized cats and rabbits, using the tracer microsphere method. In cats, the calcium antagonist isradipine reduced AV-shunt flow; verapamil showed a similar tendency and nicardipine was without effect. Dihydralazine strongly increased, but nitroglycerin and dipyridamole decreased AV-shunt flow. In rabbits, the effects of isradipine and verapamil were similar to those seen in cats. Sodium nitroprusside had no effect, whereas prazosin, minoxidil, and the potassium-channel activator cromakalim increased AV-shunt flow. The contrasting effects of drugs sharing the same mechanism of action suggest that target-tissue selectivity is more important than themore » mechanism of action. An increase of AV-shunt flow is unlikely to be beneficial but could be associated with a number of undesirable side effects. It might negatively affect migraine sufferers and, if AV-shunt dilatation shows no tolerance development, it represents an unnecessary hemodynamic burden for the heart.« less

NIST Efforts to Quality-Assure Gunpowder Measurements

NASA Technical Reports Server (NTRS)

MacCrehan, William A.; Reardon, Michelle R.

2000-01-01

In the past few years, the National Institute for Standards and Technology (NIST) has been promoting the idea of quantitatively determining the additives in smokeless gunpowder using micellar capillary electrophoresis as a means of investigating the criminal use of hand guns and pipe bombs. As a part of this effort, we have evaluated both supercritical fluid and ultrasonic solvent extractions for the quantitative recovery of nitroglycerin (NG), diphenylamine (DPA), N-nitrosodiphenylamine (NnDPA), and ethyl centralite (EC) from gunpowder. Recoveries were evaluated by repeat extraction and matrix spiking experiments. The final extraction protocol provides greater than 95 percent recoveries. To help other researches validate their own analytical method for additive determinations, NIST is exploring the development of a standard reference material, Additives in Smokeless Gunpowder. The evaluated method is being applied to two double-base (NG-containing) powders, one stabilized with diphenylamine and the other with ethyl centralite. As part of this reference material development effort, we are conducting an interlaboratory comparison exercise among the forensic and military gunpowder measurement community.

Clinical pharmacokinetics of vasodilators. Part II.

PubMed

Kirsten, R; Nelson, K; Kirsten, D; Heintz, B

1998-07-01

Stimulating cardiac beta 1-adrenoceptors with oxyfedrine causes dilatation of coronary vessels and positive inotropic effects on the myocardium. beta 1-adrenergic agonists increase coronary blood flow in nonstenotic and stenotic vessels. The main indication for the use of the phosphodiesterase inhibitors pamrinone, mirinone, enoximone and piroximone is acute treatment of severe congestive heart failure. Theophylline is indicated for the treatment of asthma, chronic obstructive pulmonary disease, apnea in preterm infants ans sleep apnea syndrome. Severe arterial occlusive disease associated with atherosclerosis can be beneficially affected by elcosanoids. These drugs must be administered parenterally and have a half-life of only a few minutes. Sublingual or buccal preparations of nitrates are the only prompt method (within 1 or 2 min) of terminating anginal pain, except for biting nifedipine capsules. The short half-life (about 2.5 min) of nitroglycerin (glyceryl trinitrate) makes long term therapy impossible. Tolerance is a problem encountered with longer-acting nitric oxide donors. Knowledge of the pharmacokinetic properties of vasodilating drugs can prevent a too sudden and severe blood pressure decrease in patients with chronic hypertension. In considering the administration of a second dose, or another drug, the time necessary for the initially administered drug to reach maximal efficacy should be taken into account. In hypertensive emergencies urapidil, sodium nitroprusside, nitroglycerin, hydralazine and phentolamine are the drugs of choice, with the addition of beta-blockers during catecholamine crisis or dissecting aortic aneurysm. Childhood hypertension is most often treated with angiotensin-converting enzyme (ACE) inhibitors or calcium antagonists, primarily nifedipine. Because of the teratogenic risk involved with ACE inhibitors, extreme caution must be exercised when prescribing for adolescent females. The propagation of health benefits to breast-fed infants, combined with more women delaying pregnancy until their fourth decade, has entailed an increase in the need for hypertension management during lactation. Low dose hydrochlorothiazide, propranolol, nifedipine and enalapril or captopril do not pose enough of a risk of preclude breastfeeding in this group. The most frequently used antihypertensive agents during pregnancy are methyldopa, labetalol and calcium channel antagonists. Methyldopa and beta-blockers are the drugs of choice for treating mild to moderate hypertension. Prazosin and hydralazine are used to treat moderate to severe hypertension and hydralazine, urapidil or labetalol are used to treat hypertensive emergencies. The use of overly aggressive antihypertensive therapy during pregnancy should be avoided so that adequate uteroplacental blood flow is maintained. Methyldopa is the only drug accepted for use during the first trimester of pregnancy.

Effect of Aldehyde Dehydrogenase 2 Gene Polymorphism on Hemodynamics After Nitroglycerin Intervention in Northern Chinese Han Population

PubMed Central

Xia, Jia-Qi; Song, Jie; Zhang, Yi; An, Ni-Na; Ding, Lei; Zhang, Zheng

2015-01-01

Background: Nitroglycerin (NTG) is one of the few immediate treatments for acute angina. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the human body that facilitates the biological metabolism of NTG. The biological mechanism of NTG serves an important function in NTG efficacy. Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different. However, data on NTG measurement by pain relief are subjective. This study aimed to investigate the influence of ALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output (CO) and systemic vascular resistance (SVR) in Northern Chinese Han population. Methods: This study selected 559 patients from the Affiliated Hospital of Qingdao University. A total of 203 patients presented with coronary heart disease (CHD) and 356 had non-CHD (NCHD) cases. All patient ALDH2 genotypes (G504A) were detected and divided into two types: Wild (GG) and mutant (GA/AA). Among the CHD group, 103 were wild-type cases, and 100 were mutant-type cases. Moreover, 196 cases were wild-type, and 160 cases were mutant type among the NCHD volunteers. A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0, 5, and 15 minute time points after medication with 0.5 mg sublingual NTG. Two CO and SVR indicators were used for a comparative analysis of all case genotypes. Results: Both CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD (F = 16.460, 15.003, P = 0.000, 0.000) and CHD groups (F = 194.482, 60.582, P = 0.000, 0.000). All CO values in the wild-type case of both NCHD and CHD groups increased, whereas those in the mutant type decreased. The CO and ΔCO differences were statistically significant (P < 0.05; P < 0.05). The SVR and ΔSVR changed between the wild- and mutant-type cases at all-time points in both NCHD and CHD groups had statistically significant differences (P < 0.05; P < 0.05). Conclusion: ALDH2 (G504A) gene polymorphism is associated with changes in noninvasive hemodynamic parameters (i.e. CO and SVR) after intervention with sublingual NTG. This gene polymorphism may influence the effect of NTG intervention on Northern Chinese Han population. PMID:25591559

Puerarin injection for treatment of unstable angina pectoris: a meta-analysis and systematic review

PubMed Central

Gao, Zhisheng; Wei, Baozhu; Qian, Cheng

2015-01-01

Background: Puerarin is an effective ingredient isolated from Radix Puerariae, a leguminous plant. In China, a large number of early studies suggest that puerarin may be used in the treatment of coronary heart disease. In recent years, puerarin injection has been widely used to treat coronary heart disease and angina pectoris. Objective: To systematically evaluate the clinical efficacy and safety of puerarin injection in the treatment of unstable angina pectoris (UAP). Methods: Data were retrieved from digital databases, including PubMed, Excerpt Medica Database (EMBASE), China Biology Medicine (CBM), the Cochrane Library, and Chinese databases. Results: Compared with patients who were treated with conventional Western medicines alone, the patients who were treated with conventional Western medicines in combination with puerarin injection exhibited significant improvements in the incidence of angina pectoris, electrocardiogram findings, nitroglycerin consumption and plasma endothelin levels. Conclusions: Strong evidence suggests that, the use of puerarin in combination with conventional Western medicines is a better treatment option for treating UAP, compared with the use of conventional Western medicines alone. PMID:26628941

[Acute brain expansion during emergency neck clipping surgery for cerebral aneurysms in a patient with dilated cardiomyopathy].

PubMed

Nakao, M; Kawaguchi, R; Nakatani, K; Niinai, H; Takezaki, T; Hanaki, C

1996-06-01

A 61-year-old male with coma and undiagnosed dilated cardiomyopathy received emergency cerebral aneurysm surgery. Anesthesia was induced with thiamylal, fentanyl and vecuronium and maintained with 66% N2O and 1.0% isoflurane. Five hundred ml of 20% mannitol was infused in 30 min. At the end of the infusion, hypotension occurred. Immediately after the injection of ephedrine, acute brain swelling was observed. The operation was switched to external decompression. Post-operative echocardiography revealed the presence of dilated cardiomyopathy (DCM). The ejection fraction was 34%. Two weeks later, the second operation was scheduled. The anesthesia was induced with fentanyl, midazolam and vecuronium and maintained with N2O and 0.7% isoflurane. Nitroglycerine, lidocaine, PGE1, dopamine and dobutamine were infused throughout the operation. Five hundred ml of 20% mannitol was infused in 60 min. There were no considerable hemodynamic changes and no episode of brain expansion during operation. We conclude that the rapid infusion of mannitol can trigger acute cardiac failure and brain edema in patients with DCM.

On the combustion mechanisms of ZrH2 in double-base propellant.

PubMed

Yang, Yanjing; Zhao, Fengqi; Yuan, Zhifeng; Wang, Ying; An, Ting; Chen, Xueli; Xuan, Chunlei; Zhang, Jiankan

2017-12-13

Metal hydrides are regarded as a series of promising hydrogen-supplying fuel for solid rocket propellants. Their effects on the energetic and combustion performances of propellants are closely related to their reaction mechanisms. Here we report a first attempt to determine the reaction mechanism of ZrH 2 , a high-density metal hydride, in the combustion of a double-base propellant to evaluate its potential as a fuel. ZrH 2 is determined to possess good resistance to oxidation by nitrocellulose and nitroglycerine. Thus its combustion starts with dehydrogenation to generate H 2 and metallic Zr. Subsequently, the newly formed Zr and H 2 participate in the combustion and, especially, Zr melts and then combusts on the burning surface which favors the heat feedback to the propellant. This phenomenon is completely different from the combustion behavior of the traditional fuel Al, where the Al particles are ejected off the burning surface of the propellant to get into the luminous flame zone to burn. The findings in this work validate the potential of ZrH 2 as a hydrogen-supplying fuel for double-base propellants.

Pitfalls in 16-detector row CT of the coronary arteries.

PubMed

Nakanishi, Tadashi; Kayashima, Yasuyo; Inoue, Rintaro; Sumii, Kotaro; Gomyo, Yukihiko

2005-01-01

Recently developed 16-detector row computed tomography (CT) has been introduced as a reliable noninvasive imaging modality for evaluating the coronary arteries. In most cases, with appropriate premedication that includes beta-blockers and nitroglycerin, ideal data sets can be acquired from which to obtain excellent-quality coronary CT angiograms, most often with multiplanar reformation, thin-slab maximum intensity projection, and volume rendering. However, various artifacts associated with data creation and reformation, postprocessing methods, and image interpretation can hamper accurate diagnosis. These artifacts can be related to pulsation (nonassessable segments, pseudostenosis) as well as rhythm disorders, respiratory issues, partial volume averaging effect, high-attenuation entities, inappropriate scan pitch, contrast material enhancement, and patient body habitus. Some artifacts have already been resolved with technical advances, whereas others represent partially inherent limitations of coronary CT angiography. Familiarity with the pitfalls of coronary angiography with 16-detector row CT, coupled with the knowledge of both the normal anatomy and anatomic variants of the coronary arteries, can almost always help radiologists avoid interpretive errors in the diagnosis of coronary artery stenosis. (c) RSNA, 2005.

Left ventricular function abnormalities as a manifestation of silent myocardial ischemia.

PubMed

Lambert, C R; Conti, C R; Pepine, C J

1986-11-01

A large body of evidence exists indicating that left ventricular dysfunction is a common occurrence in patients with severe coronary artery disease and represents silent or asymptomatic myocardial ischemia. Such dysfunction probably occurs early in the time course of every ischemic episode in patients with coronary artery disease whether symptoms are eventually manifested or not. The pathophysiology of silent versus symptomatic left ventricular dysfunction due to ischemia appears to be identical. Silent ischemia-related left ventricular dysfunction can be documented during spontaneous or stress-induced perturbations in the myocardial oxygen supply/demand ratio. It also may be detected by nitroglycerin-induced improvement in ventricular function or by salutary changes in wall motion following revascularization. Silent left ventricular dysfunction is a very early occurrence during ischemia and precedes electrocardiographic abnormalities. In this light, its existence should always be kept in mind when dealing with patients with ischemic heart disease. It can be hypothesized that because silent ischemia appears to be identical to ischemia with symptoms in a pathophysiologic sense, prognosis and treatment in both cases should be the same.

Isoflavone supplementation and endothelial function in menopausal women.

PubMed

Hale, Georgina; Paul-Labrador, Maura; Dwyer, James H; Merz, C Noel Bairey

2002-06-01

Despite strong observational evidence for a beneficial role of oestrogen in cardiovascular disease, recent trial results suggest that hormone replacement therapy (HRT) may have adverse effects in menopausal women with established coronary heart disease. Isoflavones are oestrogen analogues found in plants with oestrogen-like properties and, because of a favourable side-effect profile, may be ideal alternatives to HRT with respect to cardiovascular benefits. Endothelial function is a marker of cardiovascular health. We aimed to determine the effect of isoflavones on endothelial function using the brachial artery reactivity test. Twenty-nine healthy menopausal women underwent entry and exit brachial artery reactivity testing following randomization to 2 weeks of an oral soy isoflavone concentrate containing 80 mg of soy isoflavones (Archer Daniel Midland Inc., IL, USA) or placebo. At study exit, there was no difference between placebo and isoflavone groups with respect to flow-mediated dilation (%FMD(max)), change (entry to exit) in %FMD(max) or response to nitroglycerine (%TNG). Subgroup analyses assessing lipid and oestrogen effects did not produce any significant results. These results suggest that short-term oral isoflavone supplements do not improve endothelial function in healthy menopausal women.

Rapid Quantitative Analysis of Multiple Explosive Compound Classes on a Single Instrument via Flow-Injection Analysis Tandem Mass Spectrometry.

PubMed

Ostrinskaya, Alla; Kunz, Roderick R; Clark, Michelle; Kingsborough, Richard P; Ong, Ta-Hsuan; Deneault, Sandra

2018-05-24

A flow-injection analysis tandem mass spectrometry (FIA MSMS) method was developed for rapid quantitative analysis of 10 different inorganic and organic explosives. Performance is optimized by tailoring the ionization method (APCI/ESI), de-clustering potentials, and collision energies for each specific analyte. In doing so, a single instrument can be used to detect urea nitrate, potassium chlorate, 2,4,6-trinitrotoluene, 2,4,6-trinitrophenylmethylnitramine, triacetone triperoxide, hexamethylene triperoxide diamine, pentaerythritol tetranitrate, 1,3,5-trinitroperhydro-1,3,5-triazine, nitroglycerin, and octohy-dro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine with sensitivities all in the picogram per milliliter range. In conclusion, FIA APCI/ESI MSMS is a fast (<1 min/sample), sensitive (~pg/mL LOQ), and precise (intraday RSD < 10%) method for trace explosive detection that can play an important role in criminal and attributional forensics, counterterrorism, and environmental protection areas, and has the potential to augment or replace several of the existing explosive detection methods. © 2018 American Academy of Forensic Sciences.

A Chinese patent medicine Salvia miltiorrhiza depside salts for infusion combined with conventional treatment for patients with angina pectoris: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Zhang, Yili; Xie, Yanming; Liao, Xing; Jia, Qiulei; Chai, Yan

2017-02-15

Currently, many trials have been conducted to investigate the beneficial and harmful effects of Salvia miltiorrhiza depside salts for infusion for treating patients with angina pectoris. It is important to systematically and criticallyevaluate the existing literature into providing a pooled effect to examine outcomes of angina pectoris with Salvia miltiorrhiza depside salts for infusion. A systematic review and meta-analysis were performed to determine the clinical curative effect and safety of Salvia miltiorrhiza depside salts for infusion for angina pectoris and provide clear evidence to inform clinical practice. The Cochrane Library, MEDLINE, EMBASE, and other four electronic Chinese databases were searched to identify relevant randomized controlled trials. Methodological quality and reporting quality of eligible studies was evaluated by using the Cochrane risk-of-bias tool and CONSORT for traditional Chinese medicine respectively. Meta-analysis was performed by RevMan 5.3 software. Fifty-six randomized controlled trials involving 5503 patients were included. Most of the trials were classified as having an unclear risk of bias because of poor reported methodology. The main outcomes are improvements in angina symptoms, ECG improvement and reduction of nitroglycerin use. CHD mortality or rate of CHD events was not reported in any trial. Meta-analysis showed that Salvia miltiorrhiza depside salts for infusion combined with conventional treatment was better than conventional treatment alone in improving angina symptoms (RR= 1.28, 95% CI 1.24 to 1.31, p < 0.00001), the frequency of angina attack (time/week)(WMD=-1.47, 95% CI -2.16 to -0.78), reducing clinical symptom scores (WMD=-0.55, 95% CI -0.57 to -0.53, p < 0.000011), increasing physical limitation scores (WMD= 7.68, 95% CI 1.48 to 13.88, p = 0.02), improving ECG (RR= 1.32,95% CI 1.27 to 1.38, p < 0.00001) and reducing dosage of nitroglycerin (RR= 1.50, 95% CI: 1.26 to 1.77, p < 0.00001). In addition, Egger's regression tests was found there was publication bias (Kendall' tau= 0.36, p < 0.01). The current systematic review indicates relevant evidence for Salvia miltiorrhiza depside salts for infusion combined with conventional treatments treating patient with angina pectoris. However, the results should be interpreted with caution due to the low methodological quality, the risk of publication bias, lack of important clinically relevant outcomes and inadequate reporting on adverse events of the included trials. International methodological and reporting standards could help researchers conduct well designed trials and generate better evidence for Salvia miltiorrhiza depside salts for infusion. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Determining fate and transport parameters for nitroglycerine, 2,4-dinitrotoluine, and nitroguanidine in soils

NASA Astrophysics Data System (ADS)

Gosch, D. L.; Dontsova, K.; Chorover, J.; Ferré, T.; Taylor, S.

2010-12-01

During military operations, a small fraction of propellant mass is not consumed during firing and is deposited onto the ground surface (Jenkins et al., 2006). Soluble propellant constituents can be released from particulate residues into the environment. Propellant constituents of interest for this study are nitroglycerine (NG), 2,4-dinitrotoluine (2,4-DNT), 2,6-dinitrotoluine (2,6-DNT), and nitroguanidine (NQ). The goal of this work is to determine fate and transport parameters for these constituents in three soils that represent a range of geographic locations and soil properties. This supports a companion study that looks at dissolution of NG, 2,4-DNT, 2,6-DNT, and NQ from fired and unfired solid propellant formulations and their transport in soils. The three soils selected for the study are Catlin silt loam (fine-silty, mixed, mesic, superactive Oxyaquic Argiudoll), Plymouth sandy loam (mesic, coated Typic Quartzipsamment), and Sassafras loam (fine loamy, siliceous, mesic Typic Hapudult). Two of these soils, Plymouth sandy loam and Sassafras loam, were collected on military installations. Linear adsorption coefficients and transformation rates of propellant constituents were determined in batch kinetic experiments. Soils were mixed with propellant constituent solutions (2 mg L-1) at 4:1 solution/soil mass ratio and equilibrated for 0, 1, 2, 6, 12, 24, 48, and 120 hr at which time samples were centrifuged and supernatant solutions were analyzed for target compounds by high performance liquid chromatography (HPLC) using U.S. EPA Method 8330b for NG, 2,4-DNT, and 2,6-DNT, and Walsh (1989) method for NQ. Adsorption and transformation of propellant constituents were determined from the decrease in solution concentration of these compounds. It was determined that all studied compounds were subjected to sorption by the solid phase and degradation. Catlin soil, with finer texture and high organic matter content, influenced solution concentration of NG, 2,4-DNT, 2,6-DNT, and NQ to the greatest extent. Estimated fate and transport parameters will support ongoing release and column transport studies and will allow environmental managers on military installations to better estimate potential for propellant constituent transport off-site. Jenkins, T.F., A.D. Hewitt, C.L. Grant, S. Thiboutot, G. Ampleman, M.E. Walsh, T.A. Ranney, C.A. Ramsey, A.J. Palazzo, and J.C. Pennington. 2006. Identity and distribution of residues of energetic compounds at army live-fire training ranges. Chemosphere 63:1280-1290. Walsh, M.E. 1989. Analytical Methods for Determining Nitroguanidine in Soil and Water. Special Report 89-35. U.S. Army Cold Regions Research and Engineering Laboratory, Hanover, NH.

Nimodipine prevents memory impairment caused by nitroglycerin-induced hypotension in adult mice.

PubMed

Bekker, Alex; Haile, Michael; Li, Yong-Sheng; Galoyan, Samuel; Garcia, Edwardo; Quartermain, David; Kamer, Angela; Blanck, Thomas

2009-12-01

Hypotension and a resultant decrease in cerebral blood flow have been implicated in the development of cognitive dysfunction. We tested the hypothesis that nimodipine (NIMO) administered at the onset of nitroglycerin (NTG)-induced hypotension would preserve long-term associative memory. The passive avoidance (PA) paradigm was used to assess memory retention. For PA training, latencies (seconds) were recorded for entry from a suspended platform into a Plexiglas tube where a shock was automatically delivered. Latencies were recorded 48 h later for a testing trial. Ninety-six Swiss-Webster mice (30-35 g, 6-8 wk), were randomized into 6 groups 1) saline (control), 2) NTG immediately after learning, 3) NTG 3 h after learning, 4) NTG and NIMO, 5) vehicle, and 6) NIMO alone. The extent of hypotension and changes in brain tissue oxygenation (PbtO(2)) and in cerebral blood flow were studied in a separate group of animals. All groups exhibited similar training latencies (17.0 +/- 4.6 s). Mice subjected to hypotensive episodes showed a significant decrease in latency time (178 +/- 156 s) compared with those injected with saline, NTG + NIMO, or delayed NTG (580 +/- 81 s, 557 +/- 67 s, and 493 +/- 146 s, respectively). A Kruskal-Wallis 1-way analysis of variance indicated a significant difference among the 4 treatment groups (H = 15.34; P < 0.001). In a separate group of mice not subjected to behavioral studies, the same dose of NTG (n = 3) and NTG + NIMO (n = 3) caused mean arterial blood pressure to decrease from 85.9 +/- 3.8 mm Hg sem to 31.6 +/- 0.8 mm Hg sem and from 86.2 +/- 3.7 mm Hg sem to 32.6 +/- 0.2 mm Hg sem, respectively. Mean arterial blood pressure in mice treated with NIMO alone decreased from 88.1 +/- 3.8 mm Hg to 80.0 +/- 2.9 mm Hg. The intergroup difference was statistically significant (P < 0.05). PbtO(2) decreased from 51.7 +/- 4.5 mm Hg sem to 33.8 +/- 5.2 mm Hg sem in the NTG group and from 38.6 +/- 6.1 mm Hg sem to 25.4 +/- 2.0 mm Hg sem in the NTG + NIMO groups, respectively. There were no significant differences among groups. In a PA retention paradigm, the injection of NTG immediately after learning produced a significant impairment of long-term associative memory in mice, whereas delayed induced hypotension had no effect. NIMO attenuated the disruption in consolidation of long-term memory caused by NTG but did not improve latency in the absence of hypotension. The observed effect of NIMO may have been attributable to the preservation of calcium homeostasis during hypotension, because there were no differences in the PbtO(2) indices among groups.

GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus.

PubMed

Wolkow, Pawel P; Kosiniak-Kamysz, Wladyslaw; Osmenda, Grzegorz; Wilk, Grzegorz; Bujak-Gizycka, Beata; Ignacak, Adam; Kanitkar, Mihir; Walus-Miarka, Malgorzata; Harrison, David G; Korbut, Ryszard; Malecki, Maciej T; Guzik, Tomasz J

2014-01-01

The genetic background of atherosclerosis in type 2 diabetes mellitus (T2DM) is complex and poorly understood. Studying genetic components of intermediate phenotypes, such as endothelial dysfunction and oxidative stress, may aid in identifying novel genetic components for atherosclerosis in diabetic patients. Five polymorphisms forming two haplotype blocks within the GTP cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin synthesis, were studied in the context of flow and nitroglycerin mediated dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations of von Willebrand factor (vWF) and malondialdehyde (MDA). Rs841 was associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641 (which form a single haplotype) were associated with both MDA (p = 0.012, p = 0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03 and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also associated with MDA (p = 0.006). Haplotype analysis confirmed the association of both haplotypes with studied variables. Genetic variation of the GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM patients.

S-Nitrosylation of Prostacyclin Synthase Instigates Nitrate Cross Tolerance In Vivo.

PubMed

Zhou, Sheng-Nan; Lu, Jun-Xiu; Wang, Xue-Qing; Shan, Mei-Rong; Miao, Zhang; Pan, Guo-Pin; Jian, Xu; Li, Peng; Ping, Song; Pang, Xin-Yan; Bai, Yong-Ping; Liu, Chao; Wang, Shuang-Xi

2018-04-19

Development of nitrate tolerance is a major drawback to nitrate therapy. Prostacyclin (PGI2) is a powerful vasodilator produced from prostaglandin (PGH2) by prostacyclin synthase (PGIS) in endothelial cells. This study was to determine the role of PGIS S-nitrosylation in nitrate tolerance induced by nitroglycerin (GTN). In endothelial cells, GTN increased PGIS S-nitrosylation and disturbed PGH2 metabolism, which were normalized by mutants of PGIS cysteine 231/441 to alanine (C231/441A). Clearance of NO by carboxy-PTIO or inhibition of S-nitrosylation by N-acetyl-cysteine decreased GTN-induced PGIS S-nitrosylation. Enforced expression of mutated PGIS with C231/441A markedly abolished GTN-induced PGIS S-nitrosylation and nitrate cross tolerance in Apoe -/- mice. Inhibition of cyclooxygenase 1 by aspirin, supplementation of PGI2 by beraprost, and inhibition of PGIS S-nitrosylation by N-acetyl-cysteine improved GTN-induced nitrate cross tolerance in rats. In patients, increased PGIS S-nitrosylation was associated with nitrate tolerance. In conclusion, GTN induces nitrate cross tolerance through PGIS S-nitrosylation at cysteine 231/441. This article is protected by copyright. All rights reserved. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Assessment of coronary artery stenosis pressure gradient by quantitative coronary arteriography in patients with coronary artery disease.

PubMed

Atar, D; Ramanujam, P S; Saunamäki, K; Haunsø, S

1994-01-01

The aim of the study described here was to correlate coronary artery (CA) stenosis pressure gradients calculated by quantitative coronary arteriography (QCA) to invasively measured transstenotic pressure drops in patients with anginal symptoms and with known or suspected coronary artery disease. Furthermore, the known mathematical models are improved by introducing (1) pressure catheter-corrected minimal stenosis area, (2) modification of flow assumptions, and (3) stenosis exit angle. Included in the study were 45 patients with 61 stenoses. The visually estimated CA lesion severity in these non-complex stenoses was in the equivocal range of 40-70%. All measurements were performed after intracoronary administration of nifedipine and nitroglycerin. Stenosis dimensions were assessed from magnified cinefilms, using hand-held calipers. Highly significant overall correlation was found between measured and calculated pressure gradients with correction for the impact of the intracoronary catheter (P < 0.00001, r = 0.84). In particular, a substantial number of stenoses with haemodynamically-insignificant pressure gradients were identified by hydrodynamic calculations. In conclusion, the great majority of the coronary artery stenoses could be classified reliably by QCA as being haemodynamically insignificant or significant, respectively.

Direct Real-Time Detection of Vapors from Explosive Compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ewing, Robert G.; Clowers, Brian H.; Atkinson, David A.

2013-10-03

The real-time detection of vapors from low volatility explosives including PETN, tetryl, RDX and nitroglycerine along with various compositions containing these substances is demonstrated. This was accomplished with an atmospheric flow tube (AFT) using a non-radioactive ionization source and coupled to a mass spectrometer. Direct vapor detection was demonstrated in less than 5 seconds at ambient temperature without sample pre-concentration. The several seconds of residence time of analytes in the AFT provides a significant opportunity for reactant ions to interact with analyte vapors to achieve ionization. This extended reaction time, combined with the selective ionization using the nitrate reactant ionsmore » (NO3- and NO3-•HNO3), enables highly sensitive explosives detection. Observed signals from diluted explosive vapors indicate detection limits below 10 ppqv using selected ion monitoring (SIM) of the explosive-nitrate adduct at m/z 349, 378, 284 and 289 for tetryl, PETN, RDX and NG respectively. Also provided is a demonstration of the vapor detection from 10 different energetic formulations, including double base propellants, plastic explosives and commercial blasting explosives using SIM for the NG, PETN and RDX product ions.« less

Development of highly sensitive and selective antibodies for the detection of the explosive pentaerythritol tetranitrate (PETN) by bioisosteric replacement.

PubMed

Hesse, Almut; Biyikal, Mustafa; Rurack, Knut; Weller, Michael G

2016-02-01

An improved antibody against the explosive pentaerythritol tetranitrate (PETN) was developed. The immunogen was designed by the concept of bioisosteric replacement, which led to an excellent polyclonal antibody with extreme selectivity and immunoassays of very good sensitivity. Compounds such as nitroglycerine, 2,4,6-trinitrotoluene, 1,3,5-trinitrobenzene, hexogen (RDX), 2,4,6-trinitroaniline, 1,3-dinitrobenzene, octogen (HMX), triacetone triperoxide, ammonium nitrate, 2,4,6-trinitrophenol and nitrobenzene were tested for potential cross-reactivity. The detection limit of a competitive enzyme-linked immunosorbent assay was determined to be around 0.5 µg/l. The dynamic range of the assay was found to be between 1 and 1000 µg/l, covering a concentration range of three decades. This work shows the successful application of the bioisosteric concept in immunochemistry by exchange of a nitroester to a carbonate diester. The antiserum might be used for the development of quick tests, biosensors, microtitration plate immunoassays, microarrays and other analytical methods for the highly sensitive detection of PETN, an explosive frequently used by terrorists, exploiting the extreme difficulty of its detection. Copyright © 2015 John Wiley & Sons, Ltd.

Propellant's differentiation using FTIR-photoacoustic detection for forensic studies of improvised explosive devices.

PubMed

Álvarez, Ángela; Yáñez, Jorge; Contreras, David; Saavedra, Renato; Sáez, Pedro; Amarasiriwardena, Dulasiri

2017-11-01

The use of propellant for making improvised explosive devices (IED) is an incipient criminal practice. Propellant can be used as initiator in explosive mixtures along with other components such as coal, ammonium nitrate, sulfur, etc. The identification of the propellant's brand used in homemade explosives can provide additional forensic information of this evidence. In this work, four of the most common propellant brands were characterized by Fourier-transform infrared photoacoustic spectroscopy (FTIR-PAS) which is a non-destructive micro-analytical technique. Spectra shows characteristic signals of typical compounds in the propellants, such as nitrocellulose, nitroglycerin, guanidine, diphenylamine, etc. The differentiation of propellant components was achieved by using FTIR-PAS combined with chemometric methods of classification. Principal component analysis (PCA) and soft independent modelling of class analogy (SIMCA) were used to achieve an effective differentiation and classification (100%) of propellant brands. Furthermore, propellant brand differentiation was also assessed using partial least squares discriminant analyses (PLS-DA) by leave one out cross (∼97%) and external (∼100%) validation method. Our results show the ability of FTIR-PAS combined with chemometric analysis to identify and differentiate propellant brands in different explosive formulations of IED. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct real-time detection of vapors from explosive compounds.

PubMed

Ewing, Robert G; Clowers, Brian H; Atkinson, David A

2013-11-19

The real-time detection of vapors from low volatility explosives including PETN, tetryl, RDX, and nitroglycerine along with various compositions containing these substances was demonstrated. This was accomplished with an atmospheric flow tube (AFT) using a nonradioactive ionization source coupled to a mass spectrometer. Direct vapor detection was accomplished in less than 5 s at ambient temperature without sample preconcentration. The several seconds of residence time of analytes in the AFT provided a significant opportunity for reactant ions to interact with analyte vapors to achieve ionization. This extended reaction time, combined with the selective ionization using the nitrate reactant ions (NO3(-) and NO3(-)·HNO3), enabled highly sensitive explosives detection from explosive vapors present in ambient laboratory air. Observed signals from diluted explosive vapors indicated detection limits below 10 ppqv using selected ion monitoring (SIM) of the explosive-nitrate adduct at m/z 349, 378, 284, and 289 for tetryl, PETN, RDX, and NG, respectively. Also provided is a demonstration of the vapor detection from 10 different energetic formulations sampled in ambient laboratory air, including double base propellants, plastic explosives, and commercial blasting explosives using SIM for the NG, PETN, and RDX product ions.

Transient left ventricular dysfunction due to coronary spasm after spinal anesthesia with bupivacaine - a case report.

PubMed

Elikowski, Waldemar; Małek-Elikowska, Małgorzata; Słomczyński, Marek; Horbacka, Karolina; Bartkowski, Jarosław; Kalawski, Bartosz

2017-10-23

Bupivacaine is a long-acting local anesthetic (LA) used for cutaneous infiltration, peripheral nerve blocks, epidural and spinal anesthesia. However, its application may result in cardiovascular complications such as: hypotension, bradycardia, cardiac arrest and toxic myocardial injury. The authors describe a 53-year-old male with a history of cigarette smoking, admitted for an elective inguinal hernia surgery. Before surgery, the patient received subarachnoid injection of bupivacaine (20 mg). After the operation, he developed transient hypotension. Blood pressure returned to normal after gelofusine infusion; no sympathomimetics were administered. The male denied chest pain; however, ECG showed ST segment elevation coexisting with left ventricular anterolateral hypokinesia and decreased longitudinal strain in echocardiography. A significant increase in troponin I level was suggestive rather of myocardial infarction than of takotsubo cardiomyopathy. Urgent coronary angiography revealed left anterior descending artery spasm, which remitted after intracoronary nitroglycerin injection. Normalization of ECG and echocardiography was observed within a few days. The authors indicate that the presented atypical adverse effect of bupivacaine manifested itself with delay and that coronary spasm proceeded without angina. A close observation of the patient after anesthetic procedure with LA should be extended over the postoperative period.

[Angina pectoris and coronary insufficiency with a normal coronary angiogram: pathophysiological principles, diagnosis and therapeutic consequences].

PubMed

Strauer, B E

1988-01-01

The clinical syndrome "coronary insufficience at normal coronary arteriogram" is found in approximately 10-20% of patients with exercise-induced coronary insufficience. In most of these cases disturbances of coronary microcirculation are present. They can appear in vascular diseases (arterial hypertension, systemic immunopathies, immune complex vasculitis, etc.), in rheological diseases (paraproteinemia, hyperlipoproteinemia, polyglobulia, etc.), and in disturbances of transport and diffusion of oxygen (carbon monoxide intoxication, methemoglobinemia, hyperlipoproteinemia). The clinical diagnosis is based on usual diagnostic programs (electrocardiogram, exercise electrocardiogram, responsiveness to nitroglycerin, etc.), as well as on newer, functionally orientated diagnostic procedures (determinations of coronary blood flow and of coronary vascular reserve, production of lactate, serological findings, histology and immune histology of peripheral arteries, measurements of viscosities in both plasma and blood, etc.). Many clinically relevant disturbances in coronary microcirculation can thus be detected and treated on a rational basis by the management of the internal main disease, that is, by the treatment of the vascular, rheological, and metabolic disorders. Persistent angina pectoris in the presence of normal coronary arteriogram represents no termination of coronary diagnostics, but moreover implies the clinical task for using diagnostic possibilities to enable functional and therapeutical assessment of coronary microcirculation.

PATIENTS' KNOWLEDGE OF MEDICAL PATCHES IN HUNGARY.

PubMed

Somogyi, Orsolya; Zelko, Romana

2016-11-01

Transdermal therapy with medical patches is a simple possibility in home medication. As the correct use of patches has a decisive impact from the point of its modulator effect.A questionnaire survey was developed to explore level of patients' knowledge of the correct use of transdermal patches. A survey was administered in thirteen Hungarian community pharmacies from October of 2012 to May of 2015. Most of the participants, men and women over 18 years of age (n = 233), used major analgesic patches (fentanyl); the remainder were given nitroglycerin, NSAID analgesics patches during the survey. For the hypothesis testing it was assumed that men were more likely to use a razor for skin depilation before patch application than women as their denser pelage hinders patch adhesion. The hypothesis testing showed no significant gender difference in razor use (X² = 0.201; p = 0.654). Pharmacists should direct patients to avoid using soap for skin cleansing before patch application because only 22 percent of the participants always avoided its use. Since only 9 tests were flawless from 233 completed questionnaires. Many patients do not understand how to correctly apply a transdermal dosage patch. Pharmacists should teach their correct application based on results.

Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction.

PubMed

Münzel, Thomas; Steven, Sebastian; Daiber, Andreas

2014-12-01

Given acutely, organic nitrates, such as nitroglycerin (GTN), isosorbide mono- and dinitrates (ISMN, ISDN), and pentaerythrityl tetranitrate (PETN), have potent vasodilator and anti-ischemic effects in patients with acute coronary syndromes, acute and chronic congestive heart failure and arterial hypertension. During long-term treatment, however, side effects such as nitrate tolerance and endothelial dysfunction occur, and therapeutic efficacy of these drugs rapidly vanishes. Recent experimental and clinical studies have revealed that organic nitrates per se are not just nitric oxide (NO) donors, but rather a quite heterogeneous group of drugs considerably differing for mechanisms underlying vasodilation and the development of endothelial dysfunction and tolerance. Based on this, we propose that the term nitrate tolerance should be avoided and more specifically the terms of GTN, ISMN and ISDN tolerance should be used. The present review summarizes preclinical and clinical data concerning organic nitrates. Here we also emphasize the consequences of chronic nitrate therapy on the supersensitivity of the vasculature to vasoconstriction and on the increased autocrine expression of endothelin. We believe that these so far rather neglected and underestimated side effects of chronic therapy with at least GTN and ISMN are clinically important. Copyright © 2014 Elsevier Inc. All rights reserved.

Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial.

PubMed

Janssens, Stefan P; Bogaert, Jan; Zalewski, Jaroslaw; Toth, Attila; Adriaenssens, Tom; Belmans, Ann; Bennett, Johan; Claus, Piet; Desmet, Walter; Dubois, Christophe; Goetschalckx, Kaatje; Sinnaeve, Peter; Vandenberghe, Katleen; Vermeersch, Pieter; Lux, Arpad; Szelid, Zsolt; Durak, Monika; Lech, Piotr; Zmudka, Krzysztof; Pokreisz, Peter; Vranckx, Pascal; Merkely, Bela; Bloch, Kenneth D; Van de Werf, Frans

2018-05-24

Inhalation of nitric oxide (iNO) during myocardial ischaemia and after reperfusion confers cardioprotection in preclinical studies via enhanced cyclic guanosine monophosphate (cGMP) signalling. We tested whether iNO reduces reperfusion injury in patients with ST-elevation myocardial infarction (STEMI; NCT01398384). We randomized in a double-blind, placebo-controlled study 250 STEMI patients to inhale oxygen with (iNO) or without (CON) 80 parts-per-million NO for 4 h following percutaneous revascularization. Primary efficacy endpoint was infarct size as a fraction of left ventricular (LV) size (IS/LVmass), assessed by delayed enhancement contrast magnetic resonance imaging (MRI). Pre-specified subgroup analysis included thrombolysis-in-myocardial-infarction flow in the infarct-related artery, troponin T levels on admission, duration of symptoms, location of culprit lesion, and intra-arterial nitroglycerine (NTG) use. Secondary efficacy endpoints included IS relative to risk area (IS/AAR), myocardial salvage index, LV functional recovery, and clinical events at 4 and 12 months. In the overall population, IS/LVmass at 48-72 h was 18.0 ± 13.4% in iNO (n = 109) and 19.4 ± 15.4% in CON [n = 116, effect size -1.524%, 95% confidence interval (95% CI) -5.28, 2.24; P = 0.427]. Subgroup analysis indicated consistency across clinical confounders of IS but significant treatment interaction with NTG (P = 0.0093) resulting in smaller IS/LVmass after iNO in NTG-naïve patients (n = 140, P < 0.05). The secondary endpoint IS/AAR was 53 ± 26% with iNO vs. 60 ± 26% in CON (effect size -6.8%, 95% CI -14.8, 1.3, P = 0.09) corresponding to a myocardial salvage index of 47 ± 26% vs. 40 ± 26%, respectively, P = 0.09. Cine-MRI showed similar LV volumes at 48-72 h, with a tendency towards smaller increases in end-systolic and end-diastolic volumes at 4 months in iNO (P = 0.048 and P = 0.06, respectively, n = 197). Inhalation of nitric oxide was safe and significantly increased cGMP plasma levels during 4 h reperfusion. The Kaplan-Meier analysis for the composite of death, recurrent ischaemia, stroke, or rehospitalizations showed a tendency toward lower event rates with iNO at 4 months and 1 year (log-rank test P = 0.10 and P = 0.06, respectively). Inhalation of NO at 80 ppm for 4 h in STEMI was safe but did not reduce infarct size relative to absolute LVmass at 48-72h. The observed functional recovery and clinical event rates at follow-up and possible interaction with nitroglycerine warrant further studies of iNO in STEMI.

Specificity of different organic nitrates to elicit NO formation in rabbit vascular tissues and organs in vivo.

PubMed Central

Mülsch, A.; Bara, A.; Mordvintcev, P.; Vanin, A.; Busse, R.

1995-01-01

1. In the present study we assessed the formation of nitric oxide (NO) from classical and thiol-containing organic nitrates in vascular tissues and organs of anaesthetized rabbits, and established a relationship between the relaxant response elicited by nitroglycerin (NTG) and NO formation in the rabbit isolated aorta. Furthermore, the effect of isolated cytochrome P450 on NO formation from organic nitrates was investigated. 2. Rabbits received diethyldithiocarbamate (DETC; 200 mg kg-1 initial bolus i.p. and 200 mg kg-1 during 20 min, i.v.) and either saline, or one of the following organic nitrates: nitroglycerin (NTG, 0.5 mg kg-1), isosorbide dinitrate (ISDN), N-(3-nitratopivaloyl)-L-cysteine ethylester (SPM 3672), S-carboxyethyl-N-(3-nitratopivaloyl)-L-cysteine ethylester (SPM 5185), at 10 mg kg-1 each. After 20 min the animals were killed, blood vessels and organs were removed, and subsequently analyzed for spin-trapped NO by cryogenic electron spin resonance (e.s.r.) spectroscopy. 3. In the saline-treated control group, NO remained below the detection limit in all vessels and organs. In contrast, all of the nitrates tested elicited measurable NO formation, which was higher in organs (liver, kidney, heart, lung, spleen) (up to 4.8 nmol g-1 20 min-1) than in blood vessels (vena cava, mesenteric bed, femoral artery, aorta) (up to 0.7 nmol g-1 20 min-1). Classical organic nitrates (NTG, ISDN) formed NO preferentially in the mesenteric bed and the vena cava, while the SPM compounds elicited comparable NO formation in veins and arteries. 4. Using a similar spin trapping technique, NO formation was assessed in vitro in phenylephrine-precontracted rabbit aortic rings. The maximal relaxation elicited by a first exposure (10 min) to NTG (0.3 to 10 microM) was positively correlated (r = 0.8) with the net increase (NTG minus basal) of NO spin-trapped during a second exposure to the same concentration of NTG in the presence of DETC. 5. Cytochrome P450 purified from rabbit liver enhanced NO formation in a NADPH-dependent fashion from NTG, but not from the other nitrates, as assessed by activation of purified soluble guanylyl cyclase. 6. We conclude that the vessel selective action of different organic nitrates in vivo reflects differences in vascular NO formation. Thus, efficient preload reduction by classical organic nitrates can be accounted for by higher NO formation in venous capacitance as compared to arterial conductance and resistance vessels. In contrast, NO is released from cysteine-containing nitrates (SPMs) to a similar extent in arteries and veins, presumably independently of an organic nitrate-specific biotransformation. Limited tissue bioavailability of NTG and ISDN might account for low NO formation in the aorta, while true differences in biotransformation seem to account for differences in NO formation in the other vascular tissues. PMID:8590999

Thiopental inhibits nitric oxide production in rat aorta.

PubMed

Castillo, C; Asbun, J; Escalante, B; Villalón, C M; López, P; Castillo, E F

1999-12-01

We studied whether thiopental affects endothelial nitric oxide dependent vasodilator responses and nitrite production (an indicator of nitric oxide production) elicited by acetylcholine, histamine, and A23187 in rat aorta (artery in which nitric oxide is the main endothelial relaxant factor). In addition, we evaluated the barbiturate effect on nitric oxide synthase (NOS) activity in both rat aorta and kidney homogenates. Thiopental (10-100 microg/mL) reversibly inhibited the endothelium-dependent relaxation elicited by acetylcholine, histamine, and A23187. On the contrary, this anesthetic did not modify the endothelium-independent but cGMP-dependent relaxation elicited by sodium nitroprusside (1 nM - 1 microM) and nitroglycerin (1 nM - 1 microM), thus excluding an effect of thiopental on guanylate cyclase of vascular smooth muscle. Thiopental (100 microg/mL) inhibited both basal (87.8+/-14.3%) and acetylcholine- or A23187-stimulated (78.6+/-3.9 and 39.7+/-5.6%, respectively) production of nitrites in aortic rings. In addition the barbiturate inhibited (100 microg/mL) the NOS (45+/-4 and 42.8+/-9%) in aortic and kidney homogenates, respectively (measured as 14C-labeled citrulline production). In conclusion, thiopental inhibition of endothelium-dependent relaxation and nitrite production in aortic rings strongly suggests an inhibitory effect on NOS. Thiopental inhibition of the NOS provides further support to this contention.

Inorganic nitrite and nitrate in cardiovascular therapy: A better alternative to organic nitrates as nitric oxide donors?

PubMed

Münzel, Thomas; Daiber, Andreas

2018-03-01

In 1867 the organic nitrite, amyl nitrite, was introduced as a therapeutic agent in the treatment of angina pectoris and was later substituted by the organic nitrate nitroglycerin (NTG). Despite having a highly potent vasodilator capacity in veins>coronary arteries>arterioles, the vasodilator effects NTG are rapidly attenuated by the development of nitrate tolerance. We and others established that NTG treatment stimulates the production of reactive oxygen species such as superoxide and peroxynitrite with subsequent marked attenuation of the NTG vasodilator potency. The nitrite anion (NO 2 - ) has more recently been characterized to possess novel pharmacotherapeutic actions such as modulation of vasodilation under hypoxic conditions, thereby providing protection in ischemia-reperfusion injury. Administration of NO 2 - /NO 3 - has also been shown to improve myocardial function in heart failure and to lower blood pressure. Despite these positive aspects there is still a great need to study inorganic nitrate and nitrite therapy in various cardiovascular diseases in prospective outcome directed studies. In case being successful, this kind of therapy would indeed represent a cheap, therefore affordable, effective cardiovascular therapy without major side effects as observed in response to therapy with organic nitrates. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Badger Army Ammunition Plant groundwater data management system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, J.P.

1994-12-31

At the Badger Army Ammunition Plant (Badger), there are currently over 200 wells that are monitored on a quarterly basis. Badger has had three active production periods since its construction in 1942. During these periods, various nitrocellulose based propellants were produced including single base artillery propellants were produced including single base artillery propellant, double base rocket propellant and BALL POWDER{reg_sign} propellant. Intermediate materials used in the manufacture of these propellants were also produced, including nitroglycerine, and sulfuric and nitric acids. To meet the challenge of managing the data in-house, a groundwater data management system (GDMS) was developed. Although such systemsmore » are commercially available, they were not able to provide the specific capabilities necessary for data management and reporting at Badger. The GDMS not only provides the routine database capabilities of data sorts and queries, but has provided an automated data reporting system as well. The reporting function alone has significantly reduced the time and efforts that would normally be associated with this task. Since the GDMS was developed at Badger, the program can be continually adapted to site specific needs. Future planned modifications include automated reconciliation, improved transfer of data to graphics software, and statistical analysis and interpretation of the data.« less

Low esophageal mucosal blood flow in patients with nutcracker esophagus

PubMed Central

Jiang, Yanfen

2015-01-01

Nutcracker esophagus (NE) is characterized by high-amplitude peristaltic esophageal contractions, and these patients often present with symptoms of “angina-like” or noncardiac chest pain. Tissue ischemia is a known cause of visceral pain, and the goal of our present study was to determine whether esophageal wall blood perfusion (EWBP) is reduced in patients with NE. Fourteen normal subjects (mean age 51 yr, 11 men) and 12 patients (mean age 53 yr, 9 men) with NE and noncardiac chest pain were investigated. The EWBP was measured continuously using a custom-designed laser Doppler probe tethered to a Bravo capsule, which anchored it to the esophageal wall. The baseline EWBP in normal subjects was 651 ± 27 perfusion units. In patients with NE, the baseline EWBP was significantly lower than in the normal subjects (451 ± 32 perfusion units). The EWBP decreased after injection of edrophonium (which increases muscle contractions) and increased following sublingual nitroglycerin administration (which relaxes muscle) in normal subjects, as well as in NE patients. Spontaneous pain events during the recording period were often associated with drops in the EWBP. We propose that low EWBP leads to hypoxia of the esophageal tissue, which may be a mechanism of esophageal pain in patients with NE. PMID:26702139

Nitric oxide signaling: classical, less classical, and nonclassical mechanisms.

PubMed

Martínez-Ruiz, Antonio; Cadenas, Susana; Lamas, Santiago

2011-07-01

Although nitric oxide (NO) was identified more than 150 years ago and its effects were clinically tested in the form of nitroglycerine, it was not until the decades of 1970-1990 that it was described as a gaseous signal transducer. Since then, a canonical pathway linked to cyclic GMP (cGMP) as its quintessential effector has been established, but other modes of action have emerged and are now part of the common body of knowledge within the field. Classical (or canonical) signaling involves the selective activation of soluble guanylate cyclase, the generation of cGMP, and the activation of specific kinases (cGMP-dependent protein kinases) by this cyclic nucleotide. Nonclassical signaling alludes to the formation of NO-induced posttranslational modifications (PTMs), especially S-nitrosylation, S-glutathionylation, and tyrosine nitration. These PTMs are governed by specific biochemical mechanisms as well as by enzymatic systems. In addition, a less classical but equally important pathway is related to the interaction between NO and mitochondrial cytochrome c oxidase, which might have important implications for cell respiration and intermediary metabolism. Cross talk trespassing these necessarily artificial conceptual boundaries is progressively being identified and hence an integrated systems biology approach to the comprehension of NO function will probably emerge in the near future. Copyright © 2011 Elsevier Inc. All rights reserved.

The binuclear form of dinitrosyl iron complexes with thiol-containing ligands in animal tissues.

PubMed

Mikoyan, Vasak D; Burgova, Evgeniya N; Borodulin, Rostislav R; Vanin, Anatoly F

2017-01-30

It has been established that treatment of mice with sodium nitrite, S-nitrosoglutathione and the water-soluble nitroglycerine derivative isosorbide dinitrate (ISDN) as NO donors initiates in vivo synthesis of significant amounts of EPR-silent binuclear dinitrosyl iron complexes (B-DNIC) with thiol-containing ligands in the liver and other tissues of experimental mice. This effect is especially apparent if NO donors are administered to mice simultaneously with the Fe 2+ -citrate complex. Similar results were obtained in experiments on isolated liver and other mouse tissues treated with gaseous NО in vitro and during stimulation of endogenous NO synthesis in the presence of inducible NO synthase. B-DNIC appeared in mouse tissues after in vitro treatment of tissue samples with an aqueous solution of diethyldithiocarbamate (DETC), which resulted in the transfer of iron-mononitrosyl fragments from B-DNIC to the thiocarbonyl group of DETC and the formation of EPR-detectable mononitrosyl iron complexes (MNIC) with DETC. EPR-Active MNIC with N-methyl-d-glucamine dithiocarbamate (MGD) were synthesized in a similar way. MNIC-MGD were also formed in the reaction of water-soluble MGD-Fe 2+ complexes with sodium nitrite, S-nitrosoglutathione and ISDN. Copyright © 2016. Published by Elsevier Inc.

[A case of coronary artery spasm during epidural anesthesia with continuous infusion of propofol].

PubMed

Inoue, Hisashi; Ogawa, Katsumi; Takano, Yoshito; Sato, Isao; Okuda, Yasuhisa

2003-07-01

A 50-year-old male patient was scheduled for left partial pulmonary resection and biopsy. The patient had neither complication nor history of ischemic heart disease. After arriving in the operation room, an epidural catheter was inserted into the epidural space at the T 4-5 intervertebral space. Anesthesia was induced with intravenous propofol 100 mg, fentanyl 100 microgram and vecuronium 6 mg and then a double lumen endotracheal tube was inserted. Anesthesia was maintained with O2 and air (FIO2 0.3-1.0), continuous infusion of propofol, intermittent intravenous administration of fentanyl and epidural injection of 1% lidocaine. Forty-five minutes after the start of operation, ECG showed an elevation of ST segment and soon it passed into ventricular tachycardia and ventricular fibrillation. The patient was treated with cardiopulmonary resuscitation. Fifteen minutes later, ECG returned to sinus rhythm but the elevation of ST segment remained. We considered that these cardiac events were due to coronary spasm, and started continuous infusion of nitroglycerin and nicorandil. One hour later, ST segment returned to normal. The possible inducing factors in this case were altered balance between sympathetic and parasympathetic nervous activity caused by infusion of propofol and epidural block, and alpha-stimulation caused by ephedrine.

Energetic contaminants inhibit plant litter decomposition in soil.

PubMed

Kuperman, Roman G; Checkai, Ronald T; Simini, Michael; Sunahara, Geoffrey I; Hawari, Jalal

2018-05-30

Individual effects of nitrogen-based energetic materials (EMs) 2,4-dinitrotoluene (2,4-DNT), 2-amino-4,6-dinitrotoluene (2-ADNT), 4-amino-2,6-dinitrotoluene (4-ADNT), nitroglycerin (NG), and 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20) on litter decomposition, an essential biologically-mediated soil process, were assessed using Orchard grass (Dactylis glomerata) straw in Sassafras sandy loam (SSL) soil, which has physicochemical characteristics that support "very high" qualitative relative bioavailability for organic chemicals. Batches of SSL soil were separately amended with individual EMs or acetone carrier control. To quantify the decomposition rates, one straw cluster was harvested from a set of randomly selected replicate containers from within each treatment, after 1, 2, 3, 4, 6, and 8 months of exposure. Results showed that soil amended with 2,4-DNT or NG inhibited litter decomposition rates based on the median effective concentration (EC50) values of 1122 mg/kg and 860 mg/kg, respectively. Exposure to 2-ADNT, 4-ADNT or CL-20 amended soil did not significantly affect litter decomposition in SSL soil at ≥ 10,000 mg/kg. These ecotoxicological data will be helpful in identifying concentrations of EMs in soil that present an acceptable ecological risk for biologically-mediated soil processes. Published by Elsevier Inc.

Effects of Moderate Aerobic Exercise Training on Vascular Health and Blood Pressure in African Americans

PubMed Central

Feairheller, Deborah L.; Diaz, Keith M.; Kashem, Mohammed A.; Thakkar, Sunny R.; Veerabhadrappa, Praveen; Sturgeon, Kathleen M.; Ling, Chenyi; Williamson, Sheara T.; Kretzschmar, Jan; Lee, Hojun; Grimm, Heather; Babbitt, Dianne M.; Vin, Charmie; Fan, Xiaoxuan; Crabbe, Deborah L.; Brown, Michael D.

2014-01-01

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, we reported six months of aerobic exercise improved inflammatory markers, flow-mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise-induced changes in vascular health and blood pressure (BP) measures; carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2yrs;21F,5M) showed improved vascular health, but no change in BP. Carotid artery IMT decreased 6.4%, plasma NO levels increased 76.6%, plasma EMP levels decreased, percent FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P <0.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (i.e., smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans. PMID:24779748

Delta-opioid receptors as targets for migraine therapy.

PubMed

Charles, Andrew; Pradhan, Amynah A

2016-06-01

The purpose of this review is to contrast the properties of the δ-opioid receptor with those of the μ-opioid receptor, which is the primary target of most currently available opioid analgesics. We also discuss preclinical evidence that indicates the potential efficacy of δ-opioid receptor agonists as migraine therapy. The use of currently available opioid analgesics is highly problematic for patients with migraine. Delta-opioid receptors have key differences from μ receptors; these differences make the δ receptor an attractive therapeutic target for migraine. Delta-opioid receptors are expressed in both the peripheral and central nervous system in anatomical regions and cell types that are believed to play a role in migraine. Delta-receptor agonists have also shown promising effects in multiple migraine models, including nitroglycerin evoked hyperalgesia and conditioned place aversion, and cortical spreading depression. Evidence from animal models indicates that activation of δ receptors is less likely to cause tolerance and dependence, and less likely to cause hyperalgesia. In addition, δ receptors may have antidepressant and anxiolytic properties that are distinct from those of μ receptors. In human studies investigating other conditions, δ-receptor agonists have been generally safe and well tolerated. Delta-opioid receptor agonists have promising potential as acute and/or preventive migraine therapies, without the problems associated with currently used opioid analgesics.

Energetics Applications for the Oil and Gas Industry

DOE PAGES

Brinsden, Mark; Boock, Andrea; Baum, Dennis

2015-08-07

Here, early motivation and use of energetic materials in the Western World by Alfred Nobel was intended to facilitate mining, construction, and demolition activities. The motivation for the work was the recognized need for a safer energetic material as an alternate to unstabilized nitroglycerine. The invention of dynamite by Nobel was widely adopted in the civilian world and brought a fortune to Nobel, resulting in the formation of the annual Nobel Prize awards, recognizing significant achievements across many fields of endeavour. Nonetheless, further development of energetics was primarily motivated by and funded for military purposes, rather than civilian usage. Andmore » indeed much investment has been given to the development and characterization of military energetics and their application. An example application is the precision shaped charge, primarily developed as a means of focusing energy in a narrow metallic jet for deep penetration of heavy armor. However, the largest costumer today and for many years for shaped charges is not the military, but rather the oil and gas industry, which has adapted the military technology for perforation of oil and gas wells. While there are similar aspects to desired penetration capabilities in both applications, there are enough differences to warrant energetics R & D focused on oil and gas industry needs.« less

Long-term use of short- and long-acting nitrates in stable angina pectoris.

PubMed

Kosmicki, Marek Antoni

2009-05-01

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

Manipulating explosive sensitivity through structural modifications in a nitrate ester system

NASA Astrophysics Data System (ADS)

Manner, Virginia

2017-06-01

Understanding how condensed phase effects influence sensitivity is essential for developing next generation insensitive high explosives. However, the ability to predictably manipulate explosive sensitivity remains an elusive goal. Explosive sensitivity has been suggested to be governed by multiple factors, from intramolecular effects such as bond dissociation energy, oxygen balance, and the electrostatic potential of reactive functional groups, to larger scale effects, such as crystal structure and hot spot formation. We have developed derivatives of the explosive pentaerythritol tetranitrate (PETN) and examined them experimentally and theoretically, in order to better understand which properties influence sensitivity. With this molecular framework, we can evaluate how small changes to the structure of the molecule influence qualities such as oxygen balance, heat of formation, heat capacity, compressibility, crystal packing, and hydrogen bonding, through techniques such as differential scanning calorimetry, x-ray crystallography, and atomistic simulation. We have also used small-scale sensitivity testing as an initial tool to screen for large and consistent differences in handling sensitivity. We will discuss the many factors that contribute to sensitivity in this series of systematically-modified molecules as well as in existing well-studied explosive systems, such as triaminotrinitrobenzene (TATB) and nitroglycerin (NG). In collaboration with: Thomas Myers, Marc Cawkwell, Edward Kober, Bryce Tappan, Geoffrey Brown, Mary Sandstrom, LOS ALAMOS NATL LAB.

sec-Butylpropylacetamide (SPD) has antimigraine properties

PubMed Central

Kaufmann, Dan; Bates, Emily A; Yagen, Boris; Bialer, Meir; Saunders, Gerald H; Wilcox, Karen; White, H Steve; Brennan, KC

2016-01-01

Background Though migraine is disabling and affects 12%–15% of the population, there are few drugs that have been developed specifically for migraine prevention. Valproic acid (VPA) is a broad-spectrum antiepileptic drug (AED) that is also used for migraine prophylaxis, but its clinical use is limited by its side effect profile. sec-Butylpropylacetamide (SPD) is a novel VPA derivative, designed to be more potent and tolerable than VPA, that has shown efficacy in animal seizure and pain models. Methods We evaluated SPD’s antimigraine potential in the cortical spreading depression (CSD) and nitroglycerin (NTG) models of migraine. To evaluate SPD’s mechanism of action, we performed whole-cell recordings on cultured cortical neurons and neuroblastoma cells. Results In the CSD model, the SPD-treated group showed a significantly lower median number of CSDs compared to controls. In the NTG-induced mechanical allodynia model, SPD dose-dependently reduced mechanical sensitivity compared to controls. SPD showed both a significant potentiation of GABA-mediated currents and a smaller but significant decrease in NMDA currents in cultured cortical neurons. Kainic acid-evoked currents and voltage-dependent sodium channel currents were not changed by SPD. Conclusions These results demonstrate SPD’s potential as a promising novel antimigraine compound, and suggest a GABAergic mechanism of action. PMID:26568161

A Case of Hypertensive Crisis without a Surge in Adrenal Hormones after Radiofrequency Ablation as a Treatment for Primary Hepatocellular Carcinoma.

PubMed

Lee, Kyung Jin; Ryu, Soo Hyung

2017-10-25

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.

Hypertensive crisis.

PubMed

Rodriguez, Maria Alexandra; Kumar, Siva K; De Caro, Matthew

2010-01-01

Hypertension is a common chronic medical condition affecting over 65 million Americans. Uncontrolled hypertension can progress to a hypertensive crisis defined as a systolic blood pressure >180 mm Hg or a diastolic blood pressure >120 mm Hg. Hypertensive crisis can be further classified as a hypertensive urgency or hypertensive emergency depending on end-organ involvement including cardiac, renal, and neurologic injury. The prompt recognition of a hypertensive emergency with the appropriate diagnostic tests and triage will lead to the adequate reduction of blood pressure, ameliorating the incidence of fatal outcomes. Severely hypertensive patients with acute end-organ damage (hypertensive emergencies) warrant admission to an intensive care unit for immediate reduction of blood pressure with a short-acting titratable intravenous antihypertensive medication. Hypertensive urgencies (severe hypertension with no or minimal end-organ damage) may in general be treated with oral antihypertensives as an outpatient. Rapid and short-lived intravenous medications commonly used are labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside, and clevidipine. Medications such as hydralazine, immediate release nifedipine, and nitroglycerin should be avoided. Sodium nitroprusside should be used with caution because of its toxicity. The risk factors and prognosticators of a hypertensive crisis are still under recognized. Physicians should perform complete evaluations in patients who present with a hypertensive crisis to effectively reverse, intervene, and correct the underlying trigger, as well as improve long-term outcomes after the episode.

Effect of nitroglycerin administration on cardio-ankle vascular index.

PubMed

Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Takahashi, Mao; Sato, Shuji; Noike, Hirofumi; Shirai, Kohji

2016-01-01

The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey-Kramer test was used for post hoc comparisons. In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (-1.4±0.7 vs -1.4±0.9, -1.1±0.7 vs -1.4±1.0, -0.8±0.7 vs -1.2±1.0, and -0.5±0.7 vs -1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes (normal controls vs CAD; -3±7 vs -10±11, -3±5 vs -10±11, -3±6 vs -13±10, and -1±6 vs -11±10 mmHg, respectively). ΔDiastolic BP in the normal controls was significantly higher than in the CAD patients at 5 and 10 minutes (normal controls vs CAD; -8±6 vs -4±4 and -9±4 vs -6±5 mmHg, respectively). After NTG administration, the stiffness of the arteries from the origin of the aorta to the ankle as measured by CAVI decreased in both the normal controls and CAD patients, indicating that the response of arterial smooth muscle cells to nitric oxide is preserved even in CAD patients under medication.

Nitric oxide decreases coagulation protein function in rabbits as assessed by thromboelastography.

PubMed

Nielsen, V G

2001-02-01

Nitric oxide (NO) is administered via infusion of donors such as nitroglycerin or in inhaled form for treatment of ischemia and pulmonary hypertension, respectively. In rabbits, the NO donor, DETANONOate, decreases whole blood clotting function as assessed by thromboelastographic variables (R, reaction time; alpha, angle; and G, a measure of clot strength). I hypothesized that DETANONOate-derived NO would adversely affect coagulation protein and platelet function. Blood obtained from ear arteries of conscious rabbits (n = 8) anticoagulated with sodium citrate. The blood was then incubated with 0 or 10mM DETANONOate for 30 min. After incubation and recalcification, thromboelastography was performed for 60 min under four conditions: 1) 0mM DETANONOate, 2) 0mM DETANONOate with platelet inhibition with cytochalasin D, 3) 10mM DETANONOate, and 4) 10mM DETANONOate with platelet inhibition. DETANONOate significantly (P < 0.05) increased R and decreased alpha and G in samples with or without platelet inhibition, compared with samples not exposed to DETANONOate. Lastly, the percentage of total G (G(T)) attributable to platelet function (G(P)) was significantly more in the absence of DETANONOate (G(P) = 92.3% +/- 1.6%; mean +/- SD) than after exposure to DETANONOate (G(P) = 90.2% +/- 2.3%). DETANONOate-derived NO significantly decreased coagulation protein function and platelet function. Coagulation protein function may be similarly affected in clinical situations involving the administration of NO or NO donors.

Equations of State and High-Pressure Phases of Explosives

NASA Astrophysics Data System (ADS)

Peiris, Suhithi M.; Gump, Jared C.

Energetic materials, being the collective name for explosives, propellants, pyrotechnics, and other flash-bang materials, span a wide range of composite chemical formulations. Most militarily used energetics are solids composed of particles of the pure energetic material held together by a binder. Commonly used binders include various oils, waxes, and polymers or plasticizers, and the composite is melt cast, cured, or pressed to achieve the necessary mechanical properties (gels, putties, sheets, solid blocks, etc.) of the final energetic material. Mining, demolition, and other industries use liquid energetics that are similarly composed of an actual energetic material or oxidizer together with a fuel, that is to be mixed and poured for detonation. Pure energetic materials that are commonly used are nitroglycerine, ammonium nitrate, ammonium or sodium perchlorate, trinitrotoluene (TNT), HMX, RDX, and TATB. All of them are molecular materials or molecular ions that when initiated or insulted undergoes rapid decomposition with excessive liberation of heat resulting in the formation of stable final products. When the final products are gases, and they are rapidly produced, the sudden pressure increase creates a shock wave. When decomposition is so rapid that the reaction moves through the explosive faster than the speed of sound in the unreacted explosive, the material is said to detonate. Typically, energetic materials that undergo detonation are known as high explosives (HEs) and energetic materials that burn rapidly or deflagrate are known as low explosives and/or propellants.

Cardiac arrest at high elevation with a favorable outcome.

PubMed

Yanagawa, Youichi; Omori, Kazuhiko; Takeuchi, Ikuto; Jitsuiki, Kei; Yoshizawa, Toshihiko; Ishikawa, Kouhei; Kando, Yumi; Fukata, Mutsumu; Ohsaka, Hiromichi

2017-04-01

A 36-year-old man started to climb Mount Fuji (3776m above sea level: ASL), from the Gotemba new fifth station (2400m ASL). He had no significant medical history, and this was his first attempt to climb such a high mountain. He began feeling chest discomfort but continued to climb. When he reached the ninth station of the mountain (3600mASL), he lost consciousness. One individual immediately provided basic life support using an automated external defibrillator (AED) that was located in the station. After electroshocks, he regained consciousness. He was transported to the fifth station, where an ambulance could approach, in a large crawler. When the medical staff, who were transported via helicopter and ambulance, examined him near the fifth station, he still complained of chest discomfort. A single spray of nitroglycerin and aspirin (200mg) was administered. He was transported to the Cardiac Care Unit via ambulance and helicopter under escort by a physician. A chest computed tomography angiogram indicated triple-vessel disease. He was discharged without any neurological deficits after undergoing bypass surgery. In high mountains that can be easily accessed by amateur climbers who may have cardiac disease, the placement of AED devices and the establishment of the chain of survival from the scene to the intensive care unit are essential for obtaining a favorable outcome when a climber suffers cardiac arrest. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of nitrogen-based explosives with desorption atmospheric pressure photoionization mass spectrometry.

PubMed

Kauppila, T J; Flink, A; Pukkila, J; Ketola, R A

2016-02-28

Fast methods that allow the in situ analysis of explosives from a variety of surfaces are needed in crime scene investigations and home-land security. Here, the feasibility of the ambient mass spectrometry technique desorption atmospheric pressure photoionization (DAPPI) in the analysis of the most common nitrogen-based explosives is studied. DAPPI and desorption electrospray ionization (DESI) were compared in the direct analysis of trinitrotoluene (TNT), trinitrophenol (picric acid), octogen (HMX), cyclonite (RDX), pentaerythritol tetranitrate (PETN), and nitroglycerin (NG). The effect of different additives in DAPPI dopant and in DESI spray solvent on the ionization efficiency was tested, as well as the suitability of DAPPI to detect explosives from a variety of surfaces. The analytes showed ions only in negative ion mode. With negative DAPPI, TNT and picric acid formed deprotonated molecules with all dopant systems, while RDX, HMX, PETN and NG were ionized by adduct formation. The formation of adducts was enhanced by addition of chloroform, formic acid, acetic acid or nitric acid to the DAPPI dopant. DAPPI was more sensitive than DESI for TNT, while DESI was more sensitive for HMX and picric acid. DAPPI could become an important method for the direct analysis of nitroaromatics from a variety of surfaces. For compounds that are thermally labile, or that have very low vapor pressure, however, DESI is better suited. Copyright © 2016 John Wiley & Sons, Ltd.

Low-pressure barrier discharge ion source using air as a carrier gas and its application to the analysis of drugs and explosives.

PubMed

Usmanov, Dilshadbek T; Yu, Zhan; Chen, Lee Chuin; Hiraoka, Kenzo; Yamabe, Shinichi

2016-02-01

In this work, a low-pressure air dielectric-barrier discharge (DBD) ion source using a capillary with the inner diameter of 0.115 and 12 mm long applicable to miniaturized mass spectrometers was developed. The analytes, trinitrotoluene (TNT), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), 1,3,5,7-tetranitroperhydro-1,3,5,7-tetrazocine (HMX), pentaerythritol tetranitrate (PETN), nitroglycerine (NG), hexamethylene triperoxide diamine (HMTD), caffeine, cocaine and morphine, introduced through the capillary, were ionized by a low-pressure air DBD. The ion source pressures were changed by using various sizes of the ion sampling orifice. The signal intensities of those analytes showed marked pressure dependence. TNT was detected with higher sensitivity at lower pressure but vice versa for other analytes. For all analytes, a marked signal enhancement was observed when a grounded cylindrical mesh electrode was installed in the DBD ion source. Among nine analytes, RDX, HMX, NG and PETN could be detected as cluster ions [analyte + NO3 ](-) even at low pressure and high temperature up to 180 °C. The detection indicates that these cluster ions are stable enough to survive under present experimental conditions. The unexpectedly high stabilities of these cluster ions were verified by density functional theory calculation. Copyright © 2016 John Wiley & Sons, Ltd.

Role of phosphorylated extracellular signal-regulated kinase, calcitonin gene-related peptide and cyclooxygenase-2 in experimental rat models of migraine

PubMed Central

DONG, XIAOMENG; HU, YAOZHI; JING, LONG; CHEN, JINBO

2015-01-01

Although migraine is a common neurological condition, the pathomechanism is not yet fully understood. Activation of the trigeminovascular system (TVS) has an important function in this disorder and neurogenic inflammation and central sensitization are important mechanisms underlying this condition. Nitroglycerin (NTG) infusion in rats closely mimics a universally accepted human model of migraine. Electrical stimulation of the trigeminal ganglion (ESTG) of rats can also activate TVS during a migraine attack. Numerous studies have revealed that phosphorylated extracellular signal-regulated kinase (p-ERK), calcitonin gene-related peptide (CGRP) and cyclooxygenase-2 (COX-2) are involved in pain and nociceptive pathways. However, few studies have examined whether p-ERK, CGRP and COX-2 are involved in neurogenic inflammation and central sensitization. In the present study, the expression of p-ERK, CGRP and COX-2 was detected in the dura mater, trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis in NTG-induced rats and ESTG models by immunohistochemistry. The three areas considered were crucial components of the TVS. The selective COX-2 inhibitor nimesulide was used in ESTG rats to examine the association between p-ERK, CGRP and COX-2. The results demonstrated that p-ERK, CGRP and COX-2 mediated neurogenic inflammation and central sensitization in migraine. In addition, the expression of p-ERK and CGRP was attenuated by the COX-2 inhibitor. PMID:25892078

Thyrotoxicosis-induced acute myocardial infarction due to painless thyroiditis.

PubMed

Kim, Hee Jin; Jung, Tae Sik; Hahm, Jong Ryeal; Hwang, Seok-Jae; Lee, Sang Min; Jung, Jung Hwa; Kim, Soo Kyoung; Chung, Soon Il

2011-10-01

Thyrotoxicosis influences cardiovascular hemodynamics and can induce coronary vasospasm. Patients with thyrotoxicosis-induced acute myocardial infarction (AMI) are unusual and almost all reported cases have been associated with Graves' disease. Patients with painless thyroiditis show a thyrotoxic phase during the early stages. Here we describe a very rare case of thyrotoxicosis with painless thyroiditis-induced AMI. A 35-year-old Korean man visited the emergency room for a 2-hour duration of typical AMI chest pain. The patient did not have any coronary artery disease (CAD) risk factors. The electrocardiogram showed 3 mm of ST-segment elevation in leads II, III, and aVF, which is consistent with inferior AMI. We immediately treated the patient with aspirin, clopidogrel, and nitroglycerine and performed emergent coronary angiography. Coronary angiography showed normal coronary arteries without any stenotic lesions. Consistent with AMI, cardiac enzyme levels of serum creatine kinase (CK), CK-MB, and troponin-I were also elevated. Laboratory findings showed thyrotoxicosis without any thyroid autoantibodies. A 99m-technetium scintigraphy showed markedly decreased thyroid uptake compatible with thyroiditis. We treated the patient with calcium channel blockers and nitrates. The patient spontaneously recovered normal thyroid function after 6 weeks of observation and did not complain of chest pain. Thyrotoxicosis due to painless thyroiditis provoked AMI in a young man who had no atherosclerotic coronary lesions and no CAD risk factors.

Endothelial function varies according to insulin resistance disease type.

PubMed

Beckman, Joshua A; Goldfine, Allison B; Dunaif, Andrea; Gerhard-Herman, Marie; Creager, Mark A

2007-05-01

We examined the relationship between insulin resistance and vascular function in three insulin-resistant states (type 2 diabetes, non-HIV lipodystrophic diabetes, and nondiabetic polycystic ovary syndrome [PCOS]) and in healthy control subjects. The population included 12 women with type 2 diabetes, 6 with lipodystrophic diabetes, 10 with PCOS, and 19 healthy female subjects. Metabolic measures included insulin sensitivity by the homeostasis model assessment, lipids, free fatty acids, and adiponectin. High-resolution B-mode ultrasound was used to determine endothelium-dependent and -independent vasodilation. Type 2 diabetic, liposdystrophic, and PCOS subjects were insulin resistant compared with control subjects (P = 0.001). Flow-mediated vasodilation was reduced in diabetic (3.4 +/- 1.3%) compared with control (7.3 +/- 1.1%) subjects but not in lipodystrophic (7.7 +/- 1.2%) or PCOS (9.9 +/- 0.7%) subjects (P = 0.005). Nitroglycerin-mediated vasodilation was attenuated in both diabetic (15.2 +/- 2.0%) and lipodystrophic (16.7 +/- 3.6%) subjects compared with healthy control (24.6 +/- 2.4%) and PCOS (23.2 +/- 1.8%) subjects (P = 0.019). Insulin resistance, free fatty acids, adiponectin, or C-reactive protein did not associate with vascular dysfunction. Among these different types of patients with insulin resistance, we found abnormal endothelium-dependent vasodilation only in the patients with type 2 diabetes. We postulate that variations in the mechanism of insulin resistance may affect endothelial function differently than glucose homeostasis.

Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease: a prospective randomized controlled study on putative involvement of sympathetic activity.

PubMed

Jessurun, G A; DeJongste, M J; Hautvast, R W; Tio, R A; Brouwer, J; van Lelieveld, S; Crijns, H J

1999-10-01

The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. In the control group, SCS was switched off during 4 weeks before the end of the study. The control group had no crossover period. Measurements were done at baseline, then after 4 and 8 weeks. The first periods at 4 weeks of each sequence of both groups were compared. In addition, a comparison of clinical variables was performed between the study group 4 weeks after withholding stimulation and the control group 4 weeks following randomization. A total number of 24 patients with refractory angina and an implanted spinal cord stimulator were included in the study (n = 12) and control group. Angina pectoris complaints, nitroglycerin intake, ischemia, and heart rate variability using 48-hour ambulatory electrocardiographic monitoring were assessed. In addition, neurohormonal status and symptom-limited aerobic capacity were evaluated. There was no increase of anginal complaints or ischemia after withholding stimulation. Neurohormonal levels and aerobic capacity were not altered. We conclude that there is no adverse clinical rebound phenomenon after withholding neurostimulation in patients with refractory angina pectoris.

Losartan Improves Impaired Nitric Oxide Synthase-Dependent Dilatation of Cerebral Arterioles in Type 1 Diabetic Rats

PubMed Central

Arrick, Denise M.; Sharpe, Glenda M.; Sun, Hong; Mayhan, William G.

2009-01-01

We examined whether activation of angiotensin-1 receptors (AT1R) could account for impaired responses of cerebral arterioles during Type 1 diabetes (T1D). First, we measured responses of cerebral arterioles in nondiabetic rats to eNOS-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists before and during application of angiotensin II. Next, we examined whether losartan could improve impaired responses of cerebral arterioles during T1D. In addition, we harvested cerebral microvessels for Western blot analysis of AT1R protein and measured production of superoxide anion by brain tissue under basal conditions and in response to angiotensin II in the absence or presence of losartan. We found that angiotensin II specifically impaired eNOS-dependent reactivity of cerebral arterioles. In addition, while losartan did not alter responses in nondiabetics, losartan restored impaired eNOS-dependent vasodilatation in diabetics. Further, AT1R protein was higher in diabetics compared to nondiabetics. Finally, superoxide production was higher in brain tissue from diabetics compared to nondiabetics under basal conditions, angiotensin II increased superoxide production in nondiabetics and diabetics, and losartan decreased basal (diabetics) and angiotensin II-induced production of superoxide (nondiabetics and diabetics). We suggest that activation of AT1R during T1D plays a critical role in impaired eNOS-dependent dilatation of cerebral arterioles. PMID:18400212

Impaired arterial smooth muscle cell vasodilatory function in methamphetamine users.

PubMed

Nabaei, Ghaemeh; Oveisgharan, Shahram; Ghorbani, Askar; Fatehi, Farzad

2016-11-15

Methamphetamine use is a strong risk factor for stroke. This study was designed to evaluate arterial function and structure in methamphetamine users ultrasonographically. In a cross-sectional study, 20 methamphetamine users and 21 controls, aged between 20 and 40years, were enrolled. Common carotid artery intima-media thickness (CCA-IMT) marker of early atherogenesis, flow-mediated dilatation (FMD) determinants of endothelium-dependent vasodilation, and nitroglycerine-mediated dilatation (NMD) independent marker of vasodilation were measured in two groups. There were no significant differences between the two groups regarding demographic and metabolic characteristics. The mean (±SD) CCA-IMT in methamphetamine users was 0.58±0.09mm, versus 0.59±0.07mm in the controls (p=0.84). Likewise, FMD% was not significantly different between the two groups [7.6±6.1% in methamphetamine users vs. 8.2±5.1% in the controls; p=0.72], nor were peak flow and shear rate after hyperemia. However, NMD% was considerably decreased in the methamphetamine users [8.5±7.8% in methamphetamine users vs. 13.4±6.2% in controls; p=0.03]. According to our results, NMD is reduced among otherwise healthy methamphetamine users, which represents smooth muscle dysfunction in this group. This may contribute to the high risk of stroke among methamphetamine users. Copyright © 2016 Elsevier B.V. All rights reserved.

The ACE-DD genotype is associated with endothelial dysfunction in postmenopausal women.

PubMed

Méthot, Julie; Hamelin, Bettina A; Arsenault, Marie; Bogaty, Peter; Plante, Sylvain; Poirier, Paul

2006-01-01

To evaluate the effects of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the angiotensinogen M235T and the angiotensin II type 1 receptor A1166C polymorphisms, and hormone therapy used on endothelial function in postmenopausal women without manifestation of coronary artery disease. Sixty-four postmenopausal women (42 hormone therapy users and 22 hormone therapy nonusers) without clinical manifestation of coronary artery disease were evaluated using external vascular ultrasonography to measure endothelium-dependent (hyperemic response, flow-mediated dilatation) and -independent (nitroglycerin) dilatation. Genotypes were determined by polymerase chain reaction amplification. Women with the ACE-DD genotype displayed a lower flow-mediated dilatation compared to those with the ACE-II genotype (8.4% +/- 3.9% vs 12.6% +/- 5.4%, P = 0.04). Endothelial function was not associated with the angiotensinogen M235T and anglotensin II type 1 receptor A1166C polymorphisms. ACE polymorphism seems to modulate endothelial function among postmenopausal women without hormone therapy (8.2% +/- 5.1% vs 18.4% +/- 5.9% for the DD and the II genotype, respectively, P = 0.02). However, in hormone therapy users, flow-mediated dilatation was similar according to the ACE genotypes. Our findings suggest that ACE-I/D polymorphism is related to endothelial dysfunction in postmenopausal women. Furthermore, a potential interaction between estrogen users and ACE polymorphism on endothelial function may be present.

[Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].

PubMed

Sánchez Marteles, Marta; Urrutia, Agustín

2014-03-01

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Direct Analysis in Real Time Mass Spectrometry of Potential By-Products from Homemade Nitrate Ester Explosive Synthesis

PubMed Central

Sisco, Edward; Forbes, Thomas P.

2016-01-01

This work demonstrates the coupling of direct analysis in real time (DART) ionization with time-of-flight mass spectrometry (MS) in an off-axis configuration for the trace detection and analysis of potential partially nitrated and dimerized by-products of homemade nitrate ester explosive synthesis. Five compounds relating to the synthesis of nitroglycerin (NG) and pentaerythritol tetranitrate (PETN) were examined. Deprotonated ions and adducts with molecular oxygen, nitrite, and nitrate were observed in the mass spectral responses of these compounds. A global optimum temperature of 350 °C for the by-products investigated here, enabled single nanogram to sub nanogram trace detection. Matrix effects were examined through a series of mixtures containing one or more compounds (sugar alcohol precursors, by-products, and/or explosives) across a range of mass loadings. The explosives MS responses experienced competitive ionization in the presence of all by-products. The magnitude of this influence corresponded to both the degree of by-product nitration and the relative mass loading of the by-product to the explosive. This work provides a characterization of potential by-products from homemade nitrate ester synthesis, including matrix effects and potential challenges that might arise from the trace detection of homemade explosives (HMEs) containing impurities. Detection and understanding of HME impurities and complex mixtures may provide valuable information for the screening and sourcing of homemade nitrate ester explosives. PMID:26838397

Lacosamide inhibits calcitonin gene-related peptide production and release at trigeminal level in the rat.

PubMed

Greco, M C; Capuano, A; Navarra, P; Tringali, G

2016-07-01

Several classes of drugs are effective in prevention and treatment of migraine, although they may differ among each other in their mode of action and in indications. One such class is represented by antiepileptics. Lacosamide is an approved antiepileptic drug that also shows antinociceptive activity in animal models, including analgesic efficacy in central and trigeminal pain. Calcitonin gene-related peptide (CGRP) is considered the main neuro-mediator of trigeminal signalling, playing an essential role in headache, migraine in particular. Here, we investigated the effects of lacosamide on CGRP signalling in both in vitro and ex vivo/vitro models in the rat. We assessed: (1) CGRP released from brainstem explants at baseline or after pharmacological challenges; and (2) CGRP levels in brain areas after in vivo treatments with test drugs. We found that: (1) lacosamide inhibits CGRP release from brainstem explants under basal conditions as well as after stimulation by 56 mM KCl, 10 μM veratridine or 1 μM capsaicin; and (2) the i.p. administration of nitroglycerine produces an increase in CGRP levels in the brainstem and trigeminal ganglia, which is inhibited by a pre-treatment with lacosamide. These findings provide preliminary evidence suggesting that lacosamide is able to control pain transmission under conditions affecting the trigeminal system, such as migraine. © 2015 European Pain Federation - EFIC®

Alpha 2-adrenoceptors and endothelium-dependent relaxation in canine large arteries.

PubMed Central

Angus, J. A.; Cocks, T. M.; Satoh, K.

1986-01-01

Ring preparations from the carotid, coronary, renal, mesenteric and femoral arteries of the dog were precontracted with the thromboxane mimetic U46619, after ensuring that the resting conditions were comparable from the Laplace relationship. In the presence of prazosin (1 microM) and propranolol (3 microM), noradrenaline (NA) relaxed the arteries in the order coronary greater than carotid greater than femoral greater than renal = mesenteric. When maximum relaxation to nitroglycerin (10 microM) was taken to be 100% the maximum relaxation to noradrenaline in each artery was: coronary 70%; carotid 34%; femoral 19%; renal 7% and mesenteric 2%. In endothelium-intact arteries UK14304 mimicked the relaxation responses to NA and idazoxan shifted the curves to both agonists to the right, consistent with an alpha 2-adrenoceptor classification. Substance P relaxed the arteries in the same order as for NA but showed higher efficacy i.e.: coronary 100%; carotid 80%; femoral 71% renal 49%; and mesenteric 41%. Removal of the endothelium abolished the relaxation to NA. We conclude that endothelium-dependent relaxation to NA and substance P varies greatly across 5 large arteries of the dog. This may indicate that endothelium-derived relaxing factor (EDRF) release is site-dependent or that the efficacy of EDRF on smooth muscle varies; being greatest in the coronary and weakest in the renal and mesenteric arteries. PMID:2427147

Drug Therapy for Stable Angina Pectoris.

PubMed

Rousan, Talla A; Mathew, Sunil T; Thadani, Udho

2017-03-01

Chronic stable angina pectoris refers to the predictable, reproducible occurrence of pressure or a choking sensation in the chest or adjacent areas caused by myocardial ischemia in association with physical or emotional stress, and cessation of exertion and or sublingual nitroglycerin invariably relieves the discomfort. It is a common presenting symptom of severe narrowing of one or more coronary arteries, non-obstructive coronary arteries, or even when the coronary arteries are angiographically normal. Patients often avoid activities which precipitate symptoms and have impaired quality of life. Most patients with angina pectoris can be managed with lifestyle changes, especially abstinence from smoking and regular exercise, and anti-anginal drugs. However, the choice of initial or combination antianginals as recommended in the guidelines is not evidence based. In addition, patients with stable angina due to coronary artery disease should also receive aspirin and a statin. Treatment of patients with angina and normal coronary arteries remains to be established. The aim of this article is to provide the readers not only with a guideline-based approach, which varies from one country to another, but also an individual-based approach, which takes into consideration circulatory status and the presence or absence of comorbidities in the treatment decision-making process. This manuscript primarily deals with drug therapy of stable angina pectoris and not coronary artery revascularization, which also provides angina relief but is usually reserved for patients who fail to respond to adequate drug therapy.

Effects of moderate aerobic exercise training on vascular health and blood pressure in African Americans.

PubMed

Feairheller, Deborah L; Diaz, Keith M; Kashem, Mohammed A; Thakkar, Sunny R; Veerabhadrappa, Praveen; Sturgeon, Kathleen M; Ling, Chenyi; Williamson, Sheara T; Kretzschmar, Jan; Lee, Hojun; Grimm, Heather; Babbitt, Dianne M; Vin, Charmie; Fan, Xiaoxuan; Crabbe, Deborah L; Brown, Michael D

2014-07-01

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow-mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise-induced changes in vascular health and blood pressure (BP) measures, including carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP. Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P<.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (ie, smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans. ©2014 Wiley Periodicals, Inc.

Impaired endothelium-dependent vasodilatation in women with previous gestational diabetes.

PubMed

Anastasiou, E; Lekakis, J P; Alevizaki, M; Papamichael, C M; Megas, J; Souvatzoglou, A; Stamatelopoulos, S F

1998-12-01

To assess whether otherwise healthy women with a history of gestational diabetes mellitus (GDM) may have abnormalities in endothelial function at a very early stage, before glucose intolerance occurs. A total of 33 women with previous GDM (17 nonobese [BMI < 27] and 16 obese [BMI > or = 27]) and 19 healthy nonobese women were examined. A 75-g oral glucose tolerance test was performed, and insulin levels and biochemical parameters were also measured. Using high-resolution ultrasound, we measured vasodilatory responses of the brachial artery during reactive hyperemia (endothelium-dependent vasodilatation), and after nitroglycerin administration, an endothelium-independent vasodilator. Flow-mediated dilatation (FMD) was significantly and equally decreased in both groups of women with previous GDM, compared with control subjects (1.6 +/- 3.7% in the nonobese GDM group and 1.6 +/- 2.5% in the obese GDM group vs. 10.3 +/- 4.4% in control subjects, P < 0.001). FMD correlated inversely with serum uric acid levels, BMI, serum total cholesterol, and basal insulin resistance (homeostasis model assessment). Nitrate-induced dilatation was significantly decreased only in the obese GDM group compared with control subjects, (21.4 +/- 5.1 vs. 27.9 +/- 9.5, P < 0.05). Endothelial dysfunction, which is considered as a very early index of atherogenesis, is already present in both obese and nonobese women with a history of GDM, even when they have normal glucose tolerance.

FMLP provokes coronary vasoconstriction and myocardial ischemia in rabbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillespie, M.N.; Booth, D.C.; Friedman, B.J.

Recent pathological studies of coronary arteries from humans with suspected coronary spasm have revealed an augmented intramural burden of inflammatory cells. To test the hypothesis than inappropriate activation of inflammatory cells participates in the evolution of coronary vasospasm, the present experiment employed a newly developed coronary arteriographic technique for use in pentobarbital-anesthetized rabbits to evaluate the coronary vasomotor actions of the nonselective inflammatory cell stimulant, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). In 10 of 10 animals, selective left intracoronary injection of 200 ng fMLP evoked profound left coronary narrowing accompanied in all cases by ST segment deviation and dysrhythmias. Thallium-201 scintigraphy demonstrated hypoperfusion ofmore » the left ventricular free wall and septum supplied by the spastic coronary artery. The fMLP-induced epicardial vasoconstriction, ischemic electrocardiogram (ECG) changes, and thallium perfusion defects were reversed by intravenous nitroglycerin. Neither the right coronary artery nor its distribution were influenced by left coronary injection of fMLP. Additional experiments in isolated, salt solution-perfused rabbit hearts demonstrated that fMLP failed to exert direct coronary vasoconstrictor effects. These observations indicate that the nonselective inflammatory cell stimulant, fMLP, provokes arteriographically demonstrable coronary spasm with attendant myocardial hypoperfusion and ischemic ECG changes in anesthetized rabbits. Such a model may be useful in exploring the dynamic role of inflammatory cells in development of coronary spasm.« less

Vascular Responsiveness in Adrenalectomized Rats with Corticosterone Replacement

NASA Technical Reports Server (NTRS)

Darlington, Daniel N.; Kaship, Kapil; Keil, Lanny C.; Dallman, Mary F.

1989-01-01

To determine under resting, unstressed conditions the circulating glucocorticoid concentrations that best maintain sensitivity of the vascular smooth muscle and baroreceptor responses to vasoactive agents, rats with vascular cannulas were sham-adrenalectomized (sham) or adrenalectomized (ADRX) and provided with four levels of corticosterone replacement (-100 mg fused pellets of corticosterone: cholesterol 0, 20, 40, and 80% implanted subcutaneously at the time of adrenal surgery). Changes in vascular and baroreflex responses were determined after intravenous injection of varying doses of phenylephrine and nitroglycerin with measurement of arterial blood pressure and heart rate in the conscious, chronically cannulated rats. Vascular sensitivity was decreased, and resting arterial blood pressure tended to be decreased in the adrenalectomized rats; both were restored to normal with levels of corticosterone (40%), which also maintained body weight gain, thymus weight, and plasma corticosteroid binding globulin concentrations at normal values. The baroreflex curve generated from the sham group was different from the curves generated from the ADRX+O, 20, and 40% groups, but not different from that of the ADRX+80% group, suggesting that the baroreflex is maintained by higher levels of corticosterone than are necessary for the maintenance of the other variables. These data demonstrate that physiological levels of corticosterone (40% pellet) restore vascular responsiveness, body weight, thymus weight, and transcortin levels to normal in ADRX rats, whereas higher levels (80% pellet) are necessary for restoration of the baroreflex.

Evaluation of in-channel amperometric detection using a dual-channel microchip electrophoresis device and a two-electrode potentiostat for reverse polarity separations

PubMed Central

Meneses, Diogenes; Gunasekara, Dulan B.; Pichetsurnthorn, Pann; da Silva, José A. F.; de Abreu, Fabiane C.; Lunte, Susan M.

2015-01-01

In-channel amperometric detection combined with dual-channel microchip electrophoresis is evaluated using a two-electrode isolated potentiostat for reverse polarity separations. The device consists of two separate channels with the working and reference electrodes placed at identical positions relative to the end of the channel, enabling noise subtraction. In previous reports of this configuration, normal polarity and a three-electrode detection system were used. In the two-electrode detection system described here, the electrode in the reference channel acts as both the counter and reference. The effect of electrode placement in the channels on noise and detector response was investigated using nitrite, tyrosine, and hydrogen peroxide as model compounds. The effects of electrode material and size and type of reference electrode on noise and the potential shift of hydrodynamic voltammograms for the model compounds were determined. In addition, the performance of two- and three-electrode configurations using Pt and Ag/AgCl reference electrodes was compared. Although the signal was attenuated with the Pt reference, the noise was also significantly reduced. It was found that lower LOD were obtained for all three compounds with the dual-channel configuration compared to single-channel, in-channel detection. The dual-channel method was then used for the detection of nitrite in a dermal microdialysis sample obtained from a sheep following nitroglycerin administration. PMID:25256669

Antioxidant pretreatment and reduced arterial endothelial dysfunction after diving.

PubMed

Obad, Ante; Valic, Zoran; Palada, Ivan; Brubakk, Alf O; Modun, Darko; Dujić, Zeljko

2007-12-01

We have recently shown that a single air dive leads to acute arterial vasodilation and impairment of endothelium-dependent vasodilatation in humans. Additionally we have found that predive antioxidants at the upper recommended daily allowance partially prevented some of the negative effects of the dive. In this study we prospectively evaluated the effect of long-term antioxidants at a lower RDA dose on arterial endothelial function. Eight professional male divers performed an open sea air dive to 30 msw. Brachial artery flow-mediated dilation (FMD) was assessed before and after diving. The first dive, without antioxidants, caused significant brachial arterial diameter increase from 3.85 +/- 0.55 to 4.04 +/- 0.5 mm and a significant reduction of FMD from 7.6 +/- 2.7 to 2.8 +/- 2.1%. The second dive, with antioxidants, showed unchanged arterial diameter and significant reduction of FMD from 8.11 +/- 2.4 to 6.8 +/- 1.4%. The FMD reduction was significantly less with antioxidants. Vascular smooth muscle function, assessed by nitroglycerine (endothelium-independent dilation), was unaffected by diving. This study shows that long-term antioxidant treatment at a lower RDA dose ending 3-4 h before a dive reduces the endothelial dysfunction in divers. Since the scuba dive was of a similar depth and duration to those practiced by numerous recreational divers, this study raises the possibility of routine predive supplementation with antioxidants.

Migration kinetics and mechanisms of plasticizers, stabilizers at interfaces of NEPE propellant/HTPB liner/EDPM insulation.

PubMed

Huang, Zhi-ping; Nie, Hai-ying; Zhang, Yuan-yuan; Tan, Li-min; Yin, Hua-li; Ma, Xin-gang

2012-08-30

Migration appeared in the interfaces of nitrate ester plasticized polyether (NEPE) based propellant/hydroxyl-terminated polybutadiene (HTPB) based liner/ethylene propylene terpolymer (EPDM) based insulation was studied by aging at different temperatures. The migration components were extracted with solvent and determined by high performance liquid chromatography (HPLC). The migration occurred within 1mm to the interfaces, and the apparent migration activation energy (Ea) of nitroglycerin (NG), 1,2,4-butanetriol trinitrate (BTTN) and a kind of aniline stabilizer AD in propellant, liner and insulation was calculated respectively on the basis of HPLC data. The Ea values were among 15 and 50 kJ/mol, which were much less than chemical energy, and almost the same as hydrogen bond energy. The average diffusion coefficients were in the range of 10(-19)m(2)s(-1) to 10(-16)m(2)s(-1). It seemed the faster the migration rates, the smaller the apparent migration activation energy, the larger the diffusion coefficient and the less the amount of migration. It could be explained that the migration rate and energy were affected by the molecular volume of a mobile component and its diffusion property, and the amount of migration was resulted from the molecular polarity comparability of a mobile component to the based material. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of nitroglycerin administration on cardio-ankle vascular index

PubMed Central

Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Takahashi, Mao; Sato, Shuji; Noike, Hirofumi; Shirai, Kohji

2016-01-01

Purpose The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). Subjects and methods The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey–Kramer test was used for post hoc comparisons. Results In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (−1.4±0.7 vs −1.4±0.9, −1.1±0.7 vs −1.4±1.0, −0.8±0.7 vs −1.2±1.0, and −0.5±0.7 vs −1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes (normal controls vs CAD; −3±7 vs −10±11, −3±5 vs −10±11, −3±6 vs −13±10, and −1±6 vs −11±10 mmHg, respectively). ΔDiastolic BP in the normal controls was significantly higher than in the CAD patients at 5 and 10 minutes (normal controls vs CAD; −8±6 vs −4±4 and −9±4 vs −6±5 mmHg, respectively). Conclusion After NTG administration, the stiffness of the arteries from the origin of the aorta to the ankle as measured by CAVI decreased in both the normal controls and CAD patients, indicating that the response of arterial smooth muscle cells to nitric oxide is preserved even in CAD patients under medication. PMID:27536126

Heterogeneity of peripheral blood monocytes, endothelial dysfunction and subclinical atherosclerosis in patients with systemic lupus erythematosus.

PubMed

Mikołajczyk, T P; Osmenda, G; Batko, B; Wilk, G; Krezelok, M; Skiba, D; Sliwa, T; Pryjma, J R; Guzik, T J

2016-01-01

Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular morbidity and mortality. SLE patients have increased prevalence of subclinical atherosclerosis, although the mechanisms of this observation remain unclear. Considering the emerging role of monocytes in atherosclerosis, we aimed to investigate the relationship between subclinical atherosclerosis, endothelial dysfunction and the phenotype of peripheral blood monocytes in SLE patients. We characterized the phenotype of monocyte subsets defined by the expression of CD14 and CD16 in 42 patients with SLE and 42 non-SLE controls. Using ultrasonography, intima-media thickness (IMT) of carotid arteries and brachial artery flow-mediated dilation (FMD) as well as nitroglycerin-induced dilation (NMD) were assessed. Patients with SLE had significantly, but only modestly, increased IMT when compared with non-SLE controls (median (25th/75th percentile) 0.65 (0.60/0.71) mm vs 0.60 (0.56/0.68) mm; p < 0.05). Importantly, in spite of early atherosclerotic complications in the studied SLE group, marked endothelial dysfunction was observed. CD14dimCD16+proinflammatory cell subpopulation was positively correlated with IMT in SLE patients. This phenomenon was not observed in control individuals. Interestingly, endothelial dysfunction assessed by FMD was not correlated with any of the studied monocyte subsets. Our observations suggest that CD14dimCD16+monocytes are associated with subclinical atherosclerosis in SLE, although the mechanism appears to be independent of endothelial dysfunction. © The Author(s) 2015.

Organic nitrates and nitrate tolerance--state of the art and future developments.

PubMed

Daiber, Andreas; Münzel, Thomas; Gori, Tommaso

2010-01-01

The hemodynamic and antiischemic effects of nitroglycerin (GTN) are lost upon chronic administration due to the rapid development of nitrate tolerance. The mechanism of this phenomenon has puzzled several generations of scientists, but recent findings have led to novel hypotheses. The formation of reactive oxygen and nitrogen species in the mitochondria and the subsequent inhibition of the nitrate-bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) appear to play a central role, at least for GTN, that is, bioactivated by ALDH-2. Importantly, these findings provide the opportunity to reconcile the two "traditional" hypotheses of nitrate tolerance, that is, the one postulating a decreased bioactivation and the concurrent one suggesting a role of oxidative stress. Furthermore, recent animal and human experimental studies suggest that the organic nitrates are not a homogeneous group but demonstrate a broad diversity with regard to induction of vascular dysfunction, oxidative stress, and other side effects. In the past, attempts to avoid nitrate-induced side effects have focused on administration schedules that would allow a "nitrate-free interval"; in the future, the role of co-therapies with antioxidant compounds and of activation of endogeneous protective pathways such as the heme oxygenase 1 (HO-1) will need to be explored. However, the development of new nitrates, for example, tolerance-free aminoalkyl nitrates or combination of nitrate groups with established cardiovascular drugs like ACE inhibitors or AT(1)-receptor blockers (hybrid molecules) may be of great clinical interest. Copyright © 2010 Elsevier Inc. All rights reserved.

Cardiovascular Adaptations to Long Duration Head-Down Tilt Bed Rest

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Martin, David S.; Perez, Sondar A.; Ribeiro, Christine; Stenger, Michael B.; Summers, Richard; Meck, Janice V.

2008-01-01

INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 days of bed rest, and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 minutes or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49. Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Intimal-medial thickness markedly decreased at bed rest days 21, 35 and 49. Several cardiac functional parameters including isovolumic relaxation time, ejection time and myocardial performance index were significantly increased (indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 days of bed rest. DISCUSSION: These data suggest that 6 head-down tilt bed rest alters cardiovascular structure and function in a pattern similar to short duration spaceflight. Additionally, the vascular alterations are primarily seen in the lower body, while vessels of the upper body are unaffected. KEY WORDS: spaceflight, orthostatic intolerance, hypotension, fluid-shift, plasma volume

Vascular function and cholecalciferol supplementation in CKD: A self-controlled case series.

PubMed

Kumar, Vivek; Yadav, Ashok Kumar; Singhal, Manphool; Kumar, Vinod; Lal, Anupam; Banerjee, Debasish; Gupta, Krishan Lal; Jha, Vivekanand

2018-06-01

Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3-4 CKD (J Am Soc Nephrol 28: 3100-3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300,000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 125 (OH) 2 D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH) 2 D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0-7.5%, p < 0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function. Copyright © 2018 Elsevier Ltd. All rights reserved.

Determination of nitrate esters in water samples Comparison of efficiency of solid-phase extraction and solid-phase microextraction.

PubMed

Jezová, Vera; Skládal, Jan; Eisner, Ales; Bajerová, Petra; Ventura, Karel

2007-12-07

This paper deals with comparison of efficiency of extraction techniques (solid-phase extraction, SPE and solid-phase microextraction, SPME) used for extraction of nitrate esters (ethyleneglycoldinitrate, EGDN and nitroglycerin, NG), representing the first step of the method of quantitative determination of trace concentrations of nitrate esters in water samples. EGDN and NG are subsequently determined by means of high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Optimization of SPE and SPME conditions was carried out using model water samples. Seven SPE cartridges were tested and the conditions were optimized (type of sorbent, type and volume of solvent to be used as eluent). For both nitrate esters the limit of detection (LOD) and the limit of quantification (LOQ) obtained using SPE/HPLC-UV were 0.23 microg mL(-1) and 0.70 microg mL(-1), respectively. Optimization of SPME conditions: type of SPME fibre (four fibres were tested), type and time of sorption/desorption, temperature of sorption. PDMS/DVB (polydimethylsiloxane/divinylbenzene) fibre coating proved to be suitable for extraction of EGDN and NG. For this fibre the LOD and the LOQ for both nitrate esters were 0.16 microg mL(-1) and 0.50 microg mL(-1), respectively. Optimized methods SPE/HPLC-UV and SPME/HPLC-UV were then used for quantitative determination of nitrate esters content in real water samples from the production of EGDN and NG.

Unstable Angina Treatment in Various Periods of Geomagnetic Activity

NASA Astrophysics Data System (ADS)

Parshina, S. S.; Tokayeva, L. K.; Afanasiyeva, T. N.; Samsonov, S. N.; Petrova, V. D.; Dolgova, E. M.; Manykina, V. I.; Vodolagina, E. S.

In 145 patients with unstable angina (UA) there was analized an efficiency of a drug therapy at different types of heliogeophysical activity (HA) during the 23th solar cycle. 83 patients were examined at the period of a lower HA (Kp-index 16,19±0,18), and 62 patients - at the period of a higher HA (Kp-index 17,25±0,21, p<0,05). Baseline severity of patients' condition with UA at the moment of hospitalization at the studied periods did not differ, but the effectiveness of the therapy depended on the period of HA. At the period of a higher HA antianginal effect was stronger than at the lower period of HA (2,27±0,16 points and 1,75±0,12 points, p<0,05), and the need in nitroglycerin on the background of a drug therapy disappeared for 5-7 days quicker than at the period of a lower HA. Maximal hypotensive effect at a higher HA was achieved quicker - on the 3rd day of the treatment, and at a lower HA - only up to hospital discharge (p<0,05). Blood viscosity did not normalize in both of the studied periods, but in small vessels there was noted a decrease of a BV (p<0,05). So, at a higher HA the effectiveness of a drug therapy in patients with UA is higher than at the period of a lower HA.

In vitro study on antioxidant potential of various drugs used in the perioperative period.

PubMed

Kang, M Y; Tsuchiya, M; Packer, L; Manabe, M

1998-01-01

Since surgical trauma not only intensifies the oxidative stress by generating reactive oxygen species (ROS), but also weakens the biological defense system against ROS attack, the antioxidant activity of drugs used during the perioperative period, which possibly normalizes the impaired redox state in the patient, is of fundamental importance and great clinical interest. We have applied the phycoerythrin fluorescence-based assay, in which 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-generated peroxyl radical attacks B-phycoerythrin (B-PE) to lead to a sensitive decrease in its fluorescence intensity linearly, to evaluate the antioxidant activity of major drugs in anesthetic practice. By the protective effect on B-PE fluorescence decay, the antioxidant activities of the drugs were classified into three groups: Group I drugs, which only slowed B-PE fluorescence decay (nicardipine, verapamil, diltiazem, ephedrine, aminophylline, vecuronium, lidocaine, mepivacaine, midazolam, thiamylal, droperidol, ketamine, hydroxyzine, butorphanol, prednisolone, hydrocortisone, betamethasone, dexamethasone, methylprednisolone, and furosemide); Group II drugs, which protected B-PE oxidation completely and stopped fluorescence decay in a certain duration (dopamine, epinephrine, norepinephrine, dobutamine, isoproterenol, and buprenorphine); and Group III drugs, which had no protective effect on B-PE oxidation (nitroglycerin, prostaglandin E1, neostigmine, pancuronium, suxamethonium, atropine, bupivacaine, pentazocine, and heparin). These results indicate that Group I and II drugs exert some antioxidant activity in vitro, as measured by their protection of fluorescence decay of B-PE. Careful consideration of these properties might, then, serve to facilitate more efficient drug application.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hart, A.P.; Camporesi, E.M.; Sell, T.L.

The effect of intravenous (IV) nitroglycerin (NTG) on perioperative myocardial ischemia as detected by single pass radionuclide angiocardiography was studied in 20 patients scheduled for elective coronary artery bypass grafting (CABG). Ten patients, selected at random, received IV NTG 1 microgram.kg-1.min-1 (NTG group) and 10 others, IV saline (control group). Anesthetic induction consisted of midazolam 0.2 mg.kg-1, vecuronium 0.1 mg.kg-1, and 50% N{sub 2}O in O{sub 2}. ECG leads I, II, and V5 were monitored for ST segment changes. Single pass radionuclide angiocardiography (RNA) was performed at 5 times: prior to induction, prior to tracheal intubation, and at 1, 3.5,more » and 6 min following intubation. The presence of new regional wall motion abnormalities (RWMA) was determined from each RNA study as compared with the preinduction measurement. Apart from one patient in the control group who developed a new v wave after intubation, there was no evidence of ischemia by pulmonary capillary wedge pressure. No ECG evidence of ischemia was detected in any patient. Despite this, new regional wall motion abnormalities were observed in 3 patients in the control group and 1 patient in the NTG group. Blood pressure and heart rate responses of patients with new RWMA were not significantly different from other patients. The low incidence of ischemia in this population precludes a definitive statement regarding the efficacy of IV NTG, but the lower incidence of RWMA in the NTG group suggests a protective effect.« less

Direct analysis in real time mass spectrometry of potential by-products from homemade nitrate ester explosive synthesis.

PubMed

Sisco, Edward; Forbes, Thomas P

2016-04-01

This work demonstrates the coupling of direct analysis in real time (DART) ionization with time-of-flight mass spectrometry (MS) in an off-axis configuration for the trace detection and analysis of potential partially nitrated and dimerized by-products of homemade nitrate ester explosive synthesis. Five compounds relating to the synthesis of nitroglycerin (NG) and pentaerythritol tetranitrate (PETN) were examined. Deprotonated ions and adducts with molecular oxygen, nitrite, and nitrate were observed in the mass spectral responses of these compounds. A global optimum temperature of 350 °C for the by-products investigated here enabled single nanogram to sub nanogram trace detection. Matrix effects were examined through a series of mixtures containing one or more compounds (sugar alcohol precursors, by-products, and/or explosives) across a range of mass loadings. The explosives MS responses experienced competitive ionization in the presence of all by-products. The magnitude of this influence corresponded to both the degree of by-product nitration and the relative mass loading of the by-product to the explosive. This work provides a characterization of potential by-products from homemade nitrate ester synthesis, including matrix effects and potential challenges that might arise from the trace detection of homemade explosives (HMEs) containing impurities. Detection and understanding of HME impurities and complex mixtures may provide valuable information for the screening and sourcing of homemade nitrate ester explosives. Published by Elsevier B.V.

Adult males with haemophilia have a different macrovascular and microvascular endothelial function profile compared with healthy controls.

PubMed

Sun, H; Yang, M; Fung, M; Chan, S; Jawi, M; Anderson, T; Poon, M-C; Jackson, S

2017-09-01

Endothelial function has been identified as an independent predictor of cardiovascular risk in the general population. It is unclear if the haemophilia population has a different endothelial function profile compared to the healthy population. This prospective study aims to assess if there is a difference in endothelial function between haemophilia patients and healthy controls, and the impact of endothelial function on vascular outcomes in the haemophilia population. Baseline cardiovascular risk factors and endothelial function were presented. Adult males with haemophilia A or B recruited from the British Columbia and Southern Alberta haemophilia treatment centres were matched to healthy male controls by age and cardiovascular risk factors. Macrovascular endothelial function was assessed by brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), and microvascular endothelial function was assessed by hyperaemic velocity time integral (VTI). Multivariable linear regression was used to assess the association between haemophilia and endothelial function. A total of 81 patients with haemophilia and 243 controls were included. Patients with haemophilia had a similar FMD and NMD compared to controls, although haemophilia was associated with higher FMD on multivariable analysis. Haemophilia was associated with significantly lower VTI on univariate and multivariable analyses, regardless of haemophilia type and severity. Adult males with haemophilia appear to have lower microvascular endothelial function compared to healthy controls. Future studies to assess the impact of endothelial dysfunction on cardiovascular events in the haemophilia population are needed. © 2017 John Wiley & Sons Ltd.

Oral Panax notoginseng Preparation for Coronary Heart Disease: A Systematic Review of Randomized Controlled Trials

PubMed Central

Xu, Hao; Liu, Zhaolan; Chen, Keji; Liu, Jianping

2013-01-01

This systematic review aims to evaluate current evidence for the benefit and side effect of oral Panax notoginseng preparation for coronary heart disease (CHD). We included 17 randomized clinical trials (17 papers and 1747 participants). Comparing with no intervention on the basis of conventional therapy, oral Panax notoginseng did not show significant effect on reducing cardiovascular events, but it could alleviate angina pectoris (including improving the symptoms of angina pectoris [RR 1.20; 95% CI 1.12 to 1.28; 7 trials, n = 791], improving electrocardiogram [RR 1.35; 95% CI 1.19 to 1.53; 8 trials, n = 727], decreasing the recurrence of angina pectoris [RR 0.38; 95% CI 0.16 to 0.94; 1 trials, n = 60], duration of angina pectoris [RR −1.88; 95% CI −2.08 to −1.69; 2 trials, n = 292], and dosage of nitroglycerin [MD −1.13; 95% CI −1.70 to −0.56; 2 trials, n = 212]); oral Panax notoginseng had no significant difference compared with isosorbide dinitrate on immediate effect for angina pectoris [RR 0.96; 95% CI 0.81 to 1.15; 1 trial, n = 80]. In conclusion, oral Panax notoginseng preparation could relieve angina pectoris related symptoms. However, the small sample size and potential bias of most trials influence the convincingness of this conclusion. More rigorous trials with high quality are needed to give high level of evidence, especially for the potential benefit of cardiovascular events. PMID:24023585

A Systematic Review of Topical Vasodilators for the Treatment of Intraoperative Vasospasm in Reconstructive Microsurgery.

PubMed

Vargas, Christina R; Iorio, Matthew L; Lee, Bernard T

2015-08-01

Intraoperative vasospasm during reconstructive microsurgery is common, often unpredictable, and potentially devastating with regard to flap survival. Current methods of pharmacologic management vary, and may be shifting as a result of changes in the availability of individual medications. This review aims to provide a concise examination of the published literature regarding use, efficacy, and adverse effects of the agents described for local management of vascular spasm during microsurgery. A systematic review of the literature was performed to identify articles relevant to pharmacologic treatment of intraoperative vasospasm in vivo. An additional review of the literature was performed with regard to each agent identified in order to provide clinical background information. Systematic review identified 20 articles, in which 14 vasodilator agents were evaluated. Drugs were classified into five pharmacologic categories: phosphodiesterase inhibitors (papaverine, pentoxifylline, and amrinone), local anesthetics (lidocaine), calcium channel blockers (nicardipine, verapamil, nifedipine, and magnesium sulfate), direct vasodilators (sodium nitroprusside, prostaglandin E1, nitroglycerin, and hydralazine), and alpha antagonists (phentolamine and chlorpromazine). Despite a variety of methods, these studies indicate some degree of experimental evidence of efficacy for each of these agents. Available literature regarding use of topical vasodilating agents for intraoperative management of vasospasm during microsurgery is limited and largely based on animal models, which may not reliably generalize to the reconstructive patient population. Well-controlled translational study in clinically applicable and reproducible models is needed to guide evidence-based clinical management of this important phenomenon.

Influence of tilt training on activation of the autonomic nervous system in patients with vasovagal syncope.

PubMed

Gajek, Jacek; Zyśko, Dorota; Halawa, Bogumił; Mazurek, Walentyna

2006-04-01

Tilt training is a new treatment for vasovagal syncope. Its therapeutic efficacy is thought to be the result of the desensitization of cardiopulmonary receptors, but it could be the influence of the tilt training on the activation of the autonomic nervous system as well. The study group consisted of 24 vasovagal patients (17 women and 7 men) aged 32.5 +/- 11.8 years. The diagnostic head-up tilt test was performed according to the Italian protocol with nitroglycerin if necessary. The monitoring head-up tilt test was performed according to the Westminster protocol without provocation, after 1 to 3 months of tilt training. Holter ECG recordings for HRV parameters (time and frequency domain) were obtained from selected 2-min intervals before, during and after the diagnostic and monitoring tilt test. The diagnostic test was positive in the passive phase in 6 and after provocation in 18 patients. During the training period no syncope occurred. Analysing the HRV parameters we demonstrated the following findings: I. mRR decreases immediately after assumption of a vertical position in both tests (diagnostic and monitoring) but in the diagnostic test its further decrease occurs earlier than in the monitoring test; 2. the absolute power of the HF component is greater in the early phase of tilt after tilt training than in the corresponding period in the diagnostic test. After a longer period of tilt training the activation of the sympathetic nervous system in response to the erect position is diminished.

Vasospasm of atherosclerotic coronary arteries precipitates acute ischemic myocardial damage in myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits.

PubMed

Shiomi, Masashi; Ishida, Tatsuro; Kobayashi, Tsutomu; Nitta, Norihisa; Sonoda, Akinaga; Yamada, Satoshi; Koike, Tomonari; Kuniyoshi, Nobue; Murata, Kiyoshi; Hirata, Ken-ichi; Ito, Takashi; Libby, Peter

2013-11-01

This study tested the hypothesis that vasospasm can trigger coronary plaque injury and acute ischemic myocardial damage. Myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits received an intravenous bolus of ergonovine maleate (0.45 µmol/kg) during intravenous infusion of norepinephrine (12 nmol/kg per minute) to provoke coronary spasm in vivo. After this treatment, coronary angiography demonstrated vasospasm, and the ECG showed ischemic abnormalities (ST depression/elevation and T-wave inversion) in 77% of animals (23/30). These changes normalized after nitroglycerin injection. In rabbits that demonstrated these ECG findings for >20 minutes, echocardiograms showed left ventricular wall motion abnormality. Serum levels of heart-type fatty acid-binding protein, cardiac troponin-I, and myoglobin increased markedly 4 hours after spasm provocation. In coronary lesions of myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits with provoked coronary spasm, we observed intimal injury in 60.9% in the form of endothelial cell protrusions (39.1%), denudation (30.4%), and macrophage extravasation (56.5%). Plaque disruption with luminal thrombus, however, was only seen in 2 of 23 animals (8.7%), and mural microthrombus was rarely observed (4.3%). These observations show that provocation of vasospasm in myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits associates with subsequent ischemic myocardial damage. Although treatment with spasmogens altered aspects of plaque morphology, for example, endothelial protrusion and macrophage emigration, thrombosis was rare in these animals with chronic atherosclerotic disease.

The hypertension of autonomic failure and its treatment

NASA Technical Reports Server (NTRS)

Shannon, J.; Jordan, J.; Costa, F.; Robertson, R. M.; Biaggioni, I.

1997-01-01

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.

Wink Sink

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumgardner, R.W. Jr.

1988-01-01

The Wink Sink formed on June 3, l980. Inferred precursor of the sinkhole was a solution cavity in the Permian Salado Formation formed either by natural dissolution or by water flow in an abandoned oil well. Correlation of well logs in the area indicates that the Salado Formation contains several dissolution zones. Dissolution in the middle of the Salado evaporite sequence may have resulted from ground-water flow along fractured anhydrite interbeds. The Wink Sink lies directly above the Permian Capitan reef on the margin of a natural salt dissolution trough. Other natural collapse features overlie the reef to the north.more » Hydraulic head of water in the reef is higher than the elevation of the Salado Formation but lower than the head in the Triassic Santa Rosa Sandstone, a near-surface freshwater aquifer. Fracture or cavernous permeability occurs above, within, and below the Salado Formation. Consequently, a brine-density flow may be operating: relatively fresh water moves upward through fractures under artesian pressure and dissolves salt; the denser brine moves downward under gravity flow. Alternatively, downward flow of water from freshwater aquifers above the salt may have caused dissolution. An oil well drilled into the Permian Yates Formation (with the aid of nitroglycerine) in 1928 was located within the sinkhole. The well initially produced about 80% saline water from the Permian Tansill Formation, which directly underlies the Salado. About 600 ft of casing was removed from the well when it was plugged and abandoned in 1964.« less

Nitrates for stable angina: a systematic review and meta-analysis of randomized clinical trials.

PubMed

Wei, Jiafu; Wu, Taixiang; Yang, Qing; Chen, Mao; Ni, Juan; Huang, Dejia

2011-01-07

To assess the effect (harms and benefits) of nitrates for stable angina. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Randomized controlled trials with both parallel and crossover design were included. The following outcome measures were evaluated: number of angina attacks weekly and nitroglycerin consumption, quality of life, total exercise duration, time to onset of angina and time to 1 mm ST depression. Fifty-one trials with 3595 patients meeting inclusion criteria were analyzed. Both intermittent and continuous regimens of nitrates lengthened exercise duration significantly by 31 and 53 s respectively. The number of angina attacks was significantly reduced by 2.89 episodes weekly for continuous administration and 1.5 episodes weekly for intermittent administration. With intermittent administration, increased dose provided with 21 s more length of exercise duration. With continuous administration, exercise duration was pronged more in low-dose group. Quality of life was not improved by continuous application of GTN patches and was similar between continuous and intermittent groups. In addition, 51.6% patients receiving nitrates complained with headache. Long-term administration of nitrates was beneficial for angina prophylaxis and improved exercise performance but might be ineffective for improving quality of life. With continuous regimen, low-dose nitrates were more effective than high-dose ones for improving exercise performance. By contrast, with intermittent regimen, high-dose nitrates were more effective. In addition, intermittent administration could bring zero-hour effect. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Understanding organic nitrates – a vein hope?

PubMed Central

Miller, Mark R; Wadsworth, Roger M

2009-01-01

The organic nitrate drugs, such as glyceryl trinitrate (GTN; nitroglycerin), are clinically effective in angina because of their dilator profile in veins and arteries. The exact mechanism of intracellular delivery of nitric oxide (NO), or another NO-containing species, from these compounds is not understood. However, mitochondrial aldehyde dehydrogenase (mtALDH) has recently been identified as an organic nitrate bioactivation enzyme. Nitrate tolerance, the loss of effect of organic nitrates over time, is caused by reduced bioactivation and/or generation of NO-scavenging oxygen-free radicals. In a recent issue of the British Journal of Pharmacology, Wenzl et al. show that guinea-pigs, deficient in ascorbate, also have impaired responsiveness to GTN, but nitrate tolerance was not due to ascorbate deficiency that exhibited divergent changes in mtALDH activity. Thus, the complex function of mtALDH appears to be the key to activation of GTN, the active NO species formed and the induction of tolerance that can limit clinical effectiveness of organic nitrate drugs. British Journal of Pharmacology (2009) 157, 565–567; doi:10.1111/j.1476-5381.2009.00193.x This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 The paper by Wenzl et al. is available from http://www3.interscience.wiley.com/cgi-bin/fulltext/122221718/PDFSTART PMID:19630835

Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease.

PubMed

Duffy, S J; Keaney , J F; Holbrook, M; Gokce, N; Swerdloff, P L; Frei, B; Vita, J A

2001-07-10

Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (P<0.001 by repeated-measures ANOVA). Tea consumption had no effect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.

HMX based enhanced energy LOVA gun propellant.

PubMed

Sanghavi, R R; Kamale, P J; Shaikh, M A R; Shelar, S D; Kumar, K Sunil; Singh, Amarjit

2007-05-08

Efforts to develop gun propellants with low vulnerability have recently been focused on enhancing the energy with a further improvement in its sensitivity characteristics. These propellants not only prevent catastrophic disasters due to unplanned initiation of currently used gun propellants (based on nitrate esters) but also realize enhanced energy levels to increase the muzzle velocity of the projectiles. Now, in order to replace nitroglycerine, which is highly sensitive to friction and impact, nitramines meet the requirements as they offer superior energy due to positive heat of formation, typical stoichiometry with higher decomposition temperatures and also owing to negative oxygen balance are less sensitive than stoichiometrically balanced NG. RDX has been widely reported for use in LOVA propellant. In this paper we have made an effort to present the work on scantily reported nitramine HMX based LOVA gun propellant while incorporating energetic plasticizer glycidyl azide polymer to enhance the energy level. HMX is known to be thermally stable at higher temperature than RDX and also proved to be less vulnerable to small scale shaped charge jet attack as its decomposition temperature is 270 degrees C. HMX also offers improved impulse due to its superior heat of formation (+17 kcal/mol) as compared to RDX (+14 kcal/mol). It has also been reported that a break point will not appear until 35,000 psi for propellant comprising of 5 microm HMX. Since no work has been reported in open literature regarding replacement of RDX by HMX, the present studies were carried out.

Chronic atherosclerotic mesenteric ischemia that started to develop symptoms just after anaphylaxis.

PubMed

Goto, M; Matsuzaki, M; Fuchinoue, A; Urabe, N; Kawagoe, N; Takemoto, I; Tanaka, H; Watanabe, T; Miyazaki, T; Takeuchi, M; Honda, Y; Nakanishi, K; Urita, Y; Shimada, N; Nakajima, H; Sugimoto, M; Goto, T

2012-05-01

An 83-year-old woman was referred to our emergency department with acute urticaria and sudden shortness of breath approximately 30 min after taking rectal diclofenac potassium for lumbago. After treatment with adrenaline and corticosteroids, the patient became hemodynamically stable and left the hospital on the next day. She attended our hospital 1 week after the onset of anaphylaxis because of repeated postprandial epigastric pain. No abnormal lesions were found in endoscopy. Radiographic selective catheter angiography revealed chronic mesenteric ischemia caused by atherosclerosis and abundant collateral arteries between the celiac trunk, the superior mesenteric artery and the inferior mesenteric artery. Patients with chronic mesenteric ischemia usually present with a clinical syndrome characterized by painful abdominal cramps and colic occurring typically during the postprandial phase. Fear of eating resulted in malnutrition. She was prescribed proton pump inhibitor, digestants, anticholinergic agents, serine protease inhibitors, prokinetics, antiplatelet agents and transdermal nitroglycerin intermittently, but these had no beneficial effects. It was most probable that this patient with chronic atherosclerotic mesenteric ischemia was suffering from functional abdominal pain syndrome induced by anaphylaxis. Since psychiatric disorders were associated with alterations in the processing of visceral sensation, we facilitated the patient's understanding of functional abdominal pain syndrome with the psychologist. Postprandial abdominal pain gradually faded after administration of these drugs and the patient left the hospital. Developing a satisfactory patient-physician relationship was considered more effective for the management of persistent abdominal pain caused by complicated mechanisms.

[The role of arteriovenous interrelations in the formation of clinical-pathogenetic variants of hypertonic encephalopathy].

PubMed

Belova, L A

2012-01-01

We studied 209 patients with chronic brain ischemia due to arterial hypertension (hypertonic encephalopathy). 93 patients (44.5%) had clinical-anamnestic features of constitutional phlebopathy and 116 (55.5%) had not. Based on the conception of 5 functional-morphological levels of the vascular brain system, a complex ultrasound study was conducted. The control group included 30 people without cerebrovascular pathology. In hypertonic encephalopathy, pathological processes developing in the 1st and 2nd structural-functional levels (extra- and intracerebral arteries) correspond to remodeling, that is characteristic of arterial hypertension, and do not depend on the presence of the constitutional venous insufficiency. Changes in parameters of the blood flow in the 3rd, 4th and 5th structural-functional levels of the brain's blood supply (microcirculatory bed, head venous system, jugular and spine veins) form a dopplerographic pattern of the cerebral venous dyscirculation which is mostly pronounced in constitutional phlebopathy in patients with hypertonic encephalopathy. This pattern includes the reduction of linear blood flow velocity in nitroglycerine test, lower values of the resistance index and the increase in the linear blood flow velocity in the sinus transversus and Rosenthal vein, lack of ostial valves of the inner jugular veinas well as the decrease of linear and increase in the volume blood flow velocity along it. The methodology of the system approach based on using clinical and instrumental method in the study of cerebral hemodynamics is important for treatment optimization in patients with chronic brain ischemia.

Remedial investigation/feasibility study badger army ammunition plant Baraboo, Wisconsin. Volume 2. Feasibility study report

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1994-08-01

This Feasibility Study (FS) report for the Badger Army Ammunition Plant (BAAP) in Baraboo, Wisconsin, was prepared by ABB Environmental Services, Inc. (ABB-ES) as a component of Task Order 1 of Contract DAAAl5-91-D-OOO8 with the U.S. Army Environmental Center (USAEC). This report uses the results presented in the Final Remedial Investigation (RI) report (ABB-ES, 1993a) to develop and screen alternatives for remediation of contaminated media at BAAP. The purpose of this FS report is to develop, screen, and evaluate site-specific remedial alternatives to mitigate the impact of site-derived chemicals and ultimately provide protection of human health and the environment. Preferredmore » alternatives for each site are included in this report. Based on previous environmental studies at BAAP, 11 potential hazardous waste sites were ranked according to potential contributions of hazardous chemicals to the environment. These sites were designated as Waste Management Areas because some of the sites contain multiple Solid Waste Management Units (SWMUs). The sites selected to undergo facility assessment and corrective actions are: the Propellant Burning Ground (including Landfill), Deterrent Burning Ground, existing Landfill, Settling Ponds and Spoils Disposal Area, Rocket Paste Area, Oleum Plant and Oleum Plant Pond, Nitroglycerine Pond, old Acid Area, new Acid Area, and Ballistics Pond. The USAEC added an 11th site, the Old Fuel Oil Tank, to the list in October 1989 after discovery of fuel-contaminated soils during excavation of a water line in the vicinity of the old fuel oil tank foundation.« less

Remedial investigation/feasibility study badger army ammunition plant Baraboo, Wisconsin. Volume 3. Feasibility study report (Final)

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1994-08-01

This Feasibility Study (FS) report for the Badger Army Ammunition Plant (BAAP) in Baraboo, Wisconsin, was prepared by ABB Environmental Services, Inc. (ABB-ES) as a component of Task Order 1 of Contract DAAAl5-91-D-OOO8 with the U.S. Army Environmental Center (USAEC). This report uses the results presented in the Final Remedial Investigation (RI) report (ABB-ES, 1993a) to develop and screen alternatives for remediation of contaminated media at BAAP. The purpose of this FS report is to develop, screen, and evaluate site-specific remedial alternatives to mitigate the impact of site-derived chemicals and ultimately provide protection of human health and the environment. Preferredmore » alternatives for each site are included in this report. Based on previous environmental studies at BAAP, 11 potential hazardous waste sites were ranked according to potential contributions of hazardous chemicals to the environment. These sites were designated as Waste Management Areas because some of the sites contain multiple Solid Waste Management Units (SWMUs). The sites selected to undergo facility assessment and corrective actions are: the Propellant Burning Ground (including Landfill), Deterrent Burning Ground, existing Landfill, Settling Ponds and Spoils Disposal Area, Rocket Paste Area, Oleum Plant and Oleum Plant Pond, Nitroglycerine Pond, old Acid Area, new Acid Area, and Ballistics Pond. The USAEC added an 11th site, the Old Fuel Oil Tank, to the list in October 1989 after discovery of fuel-contaminated soils during excavation of a water line in the vicinity of the old fuel oil tank foundation.« less

Remedial investigation/feasibility study badger army ammunition plant Baraboo, Wisconsin. Volume 1. Feasibility study report

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1994-08-01

This Feasibility Study (FS) report for the Badger Army Ammunition Plant (BAAP) in Baraboo, Wisconsin, was prepared by ABB Environmental Services, Inc. (ABB-ES) as a component of Task Order 1 of Contract DAAAl5-91-D-OOO8 with the U.S. Army Environmental Center (USAEC). This report uses the results presented in the Final Remedial Investigation (RI) report (ABB-ES, 1993a) to develop and screen alternatives for remediation of contaminated media at BAAP. The purpose of this FS report is to develop, screen, and evaluate site-specific remedial alternatives to mitigate the impact of site-derived chemicals and ultimately provide protection of human health and the environment. Preferredmore » alternatives for each site are included in this report. Based on previous environmental studies at BAAP, 11 potential hazardous waste sites were ranked according to potential contributions of hazardous chemicals to the environment. These sites were designated as Waste Management Areas because some of the sites contain multiple Solid Waste Management Units (SWMUs). The sites selected to undergo facility assessment and corrective actions are: the Propellant Burning Ground (including Landfill), Deterrent Burning Ground, existing Landfill, Settling Ponds and Spoils Disposal Area, Rocket Paste Area, Oleum Plant and Oleum Plant Pond, Nitroglycerine Pond, old Acid Area, new Acid Area, and Ballistics Pond. The USAEC added an 11th site, the Old Fuel Oil Tank, to the list in October 1989 after discovery of fuel-contaminated soils during excavation of a water line in the vicinity of the old fuel oil tank foundation.« less

G-suited for prevention of syncope in patients with vasovagal syncope: a pilot study.

PubMed

Rasmeehirun, Prayuth; Krittayaphong, Rungroj

2014-03-01

Vasovagal syncope (VVS) represents by far the most common cause of syncope as it is diagnosed in around 50% of all patients that come to an emergency department. Although VVS is not fatal, it can cause an injury. Even serious injuries are not common, but there are reports of serious injuries of up to 5%. There are no current studies that demonstrate the effectiveness of any treatment. Past studies found that an Anti-Gravity suit (G-suit) can increase blood pressure and has been reported to prevent orthostatic hypotension effectively in patients with diabetes. It is possible that the G-suit can prevent VVS. In the present study, the authors assessed the efficacy of G-suit for vasovagal syncope prevention. In this open-label, randomized controlled study, we used the Italian tilt protocol, namely 60 degree passive tilting followed by 0.4 mg nitroglycerin challenge when the passive phase fails to induce syncope. If test was positive, then patient was enrolled. Tilt table test was repeated to compare G-suited and no G-suited to assess efficacy of G-suit for vasovagal syncope prevention. 10 patients were enrolled. There is no difference between the control group and an experimental group. In this study there is no cardio-inhibition vasovagal syncope. Positive tilt table test occurred in 50% of the patients receiving G-suited and 100% in control group (p 0.133). G-suit is unable to prevent syncope in patients with positive tilt table test but the result is not statistically significant. However, the number of patients may be too small.

Secondary electrospray ionization-ion mobility spectrometry for explosive vapor detection.

PubMed

Tam, Maggie; Hill, Herbert H

2004-05-15

The unique capability of secondary electrospray ionization (SESI) as a nonradioactive ionization source to detect analytes in both liquid and gaseous samples was evaluated using aqueous solutions of three common military explosives: cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), nitroglycerin (NG) and pentaerythritol tetranitrate (PETN). The adducts formed between the compounds and their respective dissociation product, RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-), gave the most intense signal for the individual compound but were more sensitive to temperature than other species. These autoadducts were identified as RDX.NO(2)(-), NG.NO(3)(-), and PETN.NO(3)(-) and had maximum signal intensity at 137, 100, and 125 degrees C, respectively. The reduced mobility values of the three compounds were constant over the temperature range from 75 to 225 degrees C. The signal-to-noise ratios for RDX, NG, and PETN at 50 mg L(-1) in methanol-water were 340, 270, and 170, respectively, with a nominal noise of 8 +/- 2 pA. In addition to the investigation of autoadduct formation, the concept of doping the ionization source with nonvolatile adduct-forming agents was investigated and described for the first time. The SESI-IMS detection limit for RDX was 116 microg L(-1) in the presence of a traditional volatile chloride dopant and 5.30 microg L(-1) in the presence of a nonvolatile nitrate dopant. In addition to a lower detection limit, the nitrate dopant also produced a greater response sensitivity and a higher limit of linearity than did the traditional volatile chloride dopant.

Effect of genetic deletion and pharmacological antagonism of P2X7 receptors in a mouse animal model of migraine

PubMed Central

2014-01-01

Background Purine receptors participate in peripheral and central sensitization and are associated with migraine headache. We investigated the role of P2X7 receptor (P2X7) in a nitroglycerin (NTG)-induced mouse model of migraine. Methods Intraperitoneal NTG injection (15 mg/kg) triggered thermal hyperalgesia in the hindpaws of wild-type C57BL/6J mice, followed by the induction of c-fos in upper cervical spinal cord and trigeminal nucleus caudalis. The effect of genetic deletion of P2X7 and the selective P2X7 antagonist Brilliant Blue G (BBG) were examined on hyperalgesia and c-fos induction. Results NTG decreased the paw withdrawal threshold in both wild-type and P2X7 knockout mice. Nevertheless, subacute BBG treatment (50 mg/kg/day i.p.) completely prevented the effect of NTG in wild-type, but not in knockout mice. Whereas P2X7 deficiency differentially affected the expression of c-fos, the average number of fos-immuno-reactive neurons in trigeminal nucleus caudalis, but not in upper cervical spinal cord was lower in BBG-treated wild-type mice after NTG treatment. Conclusions Our results show that P2X7 receptors might participate in the pathogenesis of migraine, although upregulation of other P2X receptors probably compensate for the loss of its action in knockout mice. The data also suggest the therapeutic potential of P2X7 antagonists for the treatment of migraine. PMID:24885962

Measurement of oxygen tension in the ischemic myocardium using encased polargraphic oxygen electrodes.

PubMed

Barrett, J A; Lynch, V D; Balkon, J; Wolf, P S

1986-06-01

The ability to continuously monitor the delicate balance between blood flow and oxygen consumption would be a great asset in the study of myocardial ischemia. The present study was performed, in anesthetized dogs, to validate the use of encased polargraphic oxygen electrodes in the study of myocardial ischemia. Polargraphic oxygen electrodes were placed in the area to be rendered ischemic at fixed tissue depths of 3 mm (epicardium) and 9 mm (endocardium). Endocardial and epicardial oxygen tensions as well as the ratio of endocardial to epicardial oxygen tension and left circumflex coronary flow were monitored. Ischemia was induced by decreasing left circumflex coronary flow by 50%. Upon completion of a 20-min poststenotic period, endocardial pO2, endocardial/epicardial ratio, and coronary flow were significantly decreased (59 +/- 7, 52 +/- 7, and 55 +/- 4%, respectively) whereas epicardial pO2 was slightly decreased. Nitroglycerin (10 micrograms/kg, i.v.) markedly increased endocardial pO2 and endocardial/epicardial ratio above poststenotic control (13 +/- 5 mmHg and 64 +/- 10%, respectively) whereas epicardial pO2 was not significantly decreased. The increases in endocardial pO2 occurred at a point where coronary flow and mean arterial pressure were not significantly changed. Conversely, dipyridamole (125 micrograms/kg, i.v.) significantly increased coronary flow (26 +/- 2 ml/min/100 g) although it did not appreciably alter endocardial or epicardial pO2. It is concluded that encased polargraphic oxygen electrodes provide a quantitative method for determination of oxygen tension in the ischemic myocardium.

[Management of coronary artery disease at the acute phase].

PubMed

Chatot, Marion; Schiele, François

2015-03-01

In patients with acute coronary syndrome (ACS), early management is of prime importance. However, the median time taken by the patient to call the emergency services is often very long, up to 2 hours. The presence of a physician as first responder ensures good quality resuscitation in case of cardiac arrest, and allows recording of a first ECG, which can be very informative, especially in ACS without ST segment elevation. Treatment at this stage is limited to sublingual nitroglycerin and aspirin. If the first ECG shows ST segment elevation, the patient should be immediately oriented for reperfusion, usually by percutaneous coronary intervention. in the absence of ST segment elevation, the diagnosis of ACS remains unconfirmed. This does not imply that the risk is lesser, but rather that the risk cannot be evaluated accurately in the pre-hospital setting. The use of risk scores can guide the choice of management towards an invasive strategy, including coronary angiography (immediately, or within 24-72 hours). Low-risk patients are candidates for an invasive strategy, provided non-invasive tests demonstrate the presence of ischemia. During the hospital phase, antiplatelet treatment should be initiated and must be adapted to the patient bleeding and thrombotic risk. Clopidogrel is recommended only in patients who are not amenable to prasugrel or ticagrelor. Statin therapy should be initiated from day one, regardless of the initial cholesterol level, preferably with 80 mg atorvastatin. Angiotensin-converting enzyme inhibitors and beta-blockers should also be prescribed to complete the medical prescription both in-hospital and in the long term.

Closed-loop regulation of arterial pressure after acute brain death.

PubMed

Soltesz, Kristian; Sjöberg, Trygve; Jansson, Tomas; Johansson, Rolf; Robertsson, Anders; Paskevicius, Audrius; Liao, Quiming; Qin, Guangqi; Steen, Stig

2018-06-01

The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups. A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller. A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10%, during 98% of a 12 h experiment. This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.

δ-Opioid receptor agonists inhibit migraine-related hyperalgesia, aversive state and cortical spreading depression in mice

PubMed Central

Pradhan, Amynah A; Smith, Monique L; Zyuzin, Jekaterina; Charles, Andrew

2014-01-01

Background and Purpose Migraine is an extraordinarily common brain disorder for which treatment options continue to be limited. Agonists that activate the δ-opioid receptor may be promising for the treatment of migraine as they are highly effective for the treatment of chronic rather than acute pain, do not induce hyperalgesia, have low abuse potential and have anxiolytic and antidepressant properties. The aim of this study was to investigate the therapeutic potential of δ-opioid receptor agonists for migraine by characterizing their effects in mouse migraine models. Experimental Approach Mechanical hypersensitivity was assessed in mice treated with acute and chronic doses of nitroglycerin (NTG), a known human migraine trigger. Conditioned place aversion to NTG was also measured as a model of migraine-associated negative affect. In addition, we assessed evoked cortical spreading depression (CSD), an established model of migraine aura, in a thinned skull preparation. Key Results NTG evoked acute and chronic mechanical and thermal hyperalgesia in mice, as well as conditioned place aversion. Three different δ-opioid receptor agonists, SNC80, ARM390 and JNJ20788560, significantly reduced NTG-evoked hyperalgesia. SNC80 also abolished NTG-induced conditioned place aversion, suggesting that δ-opioid receptor activation may also alleviate the negative emotional state associated with migraine. We also found that SNC80 significantly attenuated CSD, a model that is considered predictive of migraine preventive therapies. Conclusions and Implications These data show that δ-opioid receptor agonists modulate multiple basic mechanisms associated with migraine, indicating that δ-opioid receptors are a promising therapeutic target for this disorder. PMID:24467301

[Nitroglycerin patch for tocolysis--a prospective randomized comparison with fenoterol by infusion].

PubMed

Schleussner, E; Richter, S; Gross, W; Kähler, C; Möller, A; Möller, U; Seewald, H J

2001-01-01

To evaluate tocolytic efficacy of transdermal glyceryl trinitrate (GTN) in comparison to fenoterol per infusionem in a prospective randomized multicenter study. 50 pregnant women between 27 and 35 weeks of gestation with preterm labour were treated with either GTN patches (0.4-0.8 mg/h) or fenoterol per infusionem (60-120 micrograms/h) up to stop of contractions or 35 weeks in maximum. The primary outcomes were the prolongation of gestation by 48 h, 7 days or up to 37 weeks of gestation as well as the neonatal outcome. The progression of cervical ripening and maternal side effects during tocolysis were assessed as secondary outcome criteria. There was no difference in successful tocolysis for 48 h and 7 days in both groups, whereas significantly more women passed 37 weeks after GTN therapy. So mean duration of pregnancy, birth weight and height were greater, whereas transfer into neonatal care unit was significantly rare after GTN. There were no differences in neonatal outcome and progression of cervical ripening during tocolysis. Maternal side effects during GTN were fewer and weaker compared with fenoterol. Circa 70% of GTN treated women had a headache temporary, whereas more than 90% of the patients with fenoterol suffered from tachycardia and tremor. Tocolytic efficacy of transdermal GTN was at least equivalent to the established beta-mimetic therapy with fenoterol. Because of the lower preterm delivery rate transfer into neonatal care for control was significantly rarer after GTN with equally good neonatal outcome in both groups. Beside the headache transdermal GTN therapy had lower maternal side effects in comparison to fenoterol.

The efficacy and hemodynamic response to Dexmedetomidine as a hypotensive agent in posterior fixation surgery following traumatic spine injury

PubMed Central

Jamaliya, Ramila H; Chinnachamy, Rajesh; Maliwad, Jyotsna; Deshmukh, Varun P; Shah, Bharat J; Chadha, Indu A

2014-01-01

Aim: This study was designed to evaluate the efficacy of dexmedetomidine (DEX) as a hypotensive agent in comparison to nitroglycerin (NTG) in posterior fixation surgery for traumatic spine injury. Materials and Methods: Forty patients ASA I or II aged 18-65 years scheduled for posterior fixation surgery were randomly assigned to receive either DEX 1 μg/kg over 10 min before induction of anesthesia followed by 0.2-0.7 μg/kg/h infusion during maintenance in DEX group or NTG 3-5 μg/kg/min infusion after induction of anesthesia in NTG group to maintain mean arterial blood pressure (MAP) between 65 and 70 mmHg. The two groups were compared for achievement of target MAP, intraoperative blood loss, and reversibility of hypotensive state. Student's t-test was used for continuous variables and chi-square test for categorical variables. P-value < 0.05 was considered significant. Results: Patients in DEX group achieved the target MAP with better heart rate (HR) control, as compared to NTG group during the period of observation. The blood loss was significantly lesser in the DEX group (422.11 ± 149.34 ml) than the NTG group (564.51 ± 160.88 ml), P = 0.01. The time to hypotension reversal in NTG group (5.63 ± 1.93 min) was lesser compared to DEX group (9.15 ± 2.16 min), P = 0.65. Conclusion: DEX is an effective and safe agent in achieving controlled hypotension in adults undergoing posterior fixation spine surgery. PMID:24803758

Extracorporeal shockwave myocardial revascularization improves clinical symptoms and left ventricular function in patients with refractory angina.

PubMed

Zuozienė, Gitana; Laucevičius, Aleksandras; Leibowitz, David

2012-01-01

Medical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. Patients with Canadian Cardiovascular Society (CCS) class III-IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. Twenty patients (four women, 16 men; mean age 64 years, range 45-83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). This study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.

[Evaluation of psychological fear in children undergoing head-up tilt test].

PubMed

Chu, Wei-Hong; Wu, Li-Jia; Wang, Cheng; Lin, Ping; Li, Fang; Zhu, Li-Ping; Ran, Jing; Zou, Run-Mei; Liu, De-Yu

2014-03-01

To investigate the effects of different tilt angles of head-up tilt test (HUTT) and different responses to HUTT on the psychological fear in children undergoing the test. HUTT was performed on children with unexplained syncope or pre-syncope (107 cases: 52 males and 55 females), aged 5.5-17.8 years (mean 12.0±2.8 years). All subjects were randomly assigned to undergo HUTT at an angle of 60°, 70° or 80°; the negative cases underwent sublingual nitroglycerin-provocation HUTT at the same tilt angle. The Wong-Baker Faces Pain Rating Scale was used for self-assessment of psychological fear in subjects during HUTT at the end point of the test. The positive rate, hemodynamic changes and distribution of response types showed no significant differences between children at tilt angles of 60°, 70° and 80° (P>0.05). The greater the tilt angle, the higher the degree of psychological fear in children undergoing the test, but there were no significant differences between them (P>0.05). The degree of psychological fear in children who showed a positive response to HUTT (n=76) was significantly higher than that in children who showed a negative response (n=31) (P<0.01). HUTT can cause psychological fear in children undergoing the test, and the degree of psychological fear increases in children tested at tilt angles from 60° to 80°, but the differences have no statistical significance. A positive response to HUTT can significantly increase the psychological fear in children.

Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics.

PubMed

Vercauteren, M; Palit, S; Soetens, F; Jacquemyn, Y; Alahuhta, S

2009-07-01

Significant side effects of tocolytic and uterotonic substances may be of concern to the anaesthesiologist. Recently, new drugs have been introduced having less side effects for both the mother and the neonate. A literature search was undertaken mainly focusing on meta-analyses, to review the possible side effects that might affect the course of anaesthesia and to suggest which precautions should be considered to prevent the occurrence of significant interactions with anaesthetic manipulations and drugs. Magnesium sulphate has a proven benefit in lowering systolic blood pressure and preventing the occurrence of eclampsia, but not as a tocolytic. beta-adrenergic agonists are being abandoned due to the availability of tocolytic agents causing less side effects. Calcium channel blockers (CCB) are frequently used but can cause major maternal cardiovascular complications. Nitroglycerin seems to be appreciated as an acute tocolytic rather than a routine substance during pre-term labour. Cyclo-oxygenase-2 inhibitors are still under investigation but their tocolytic benefit is questionable mainly due to foetal side effects. Atosiban is considered the first-choice tocolytic. With respect to oxytocic drugs, oxytocine, prostaglandines and methylergometrine may all cause serious side effects especially when combined. The cardiovascular side effects of prostaglandins and methylergometrine can be life-threatening. Both oxytocin and carbetocin have a rather low risk for maternal complications. Atosiban and CCB are at least as effective tocolytic agents as beta-mimetics but have significantly less side effects. Magnesium sulphate can cause neuromuscular blockade, especially when combined with CCB. Concerning oxytocic agents, short-acting oxyctocin and long-acting carbetocin have the least side effects as compared with prostaglandins and methylergometrine.

Current utilization of cardiac computed tomography in mainland China: A national survey.

PubMed

Liu, Kun; Hsieh, Christopher; Zhuang, Nan; Gao, Yang; Li, Zhennan; Ren, Xinshuang; Yang, Li; Zhang, Jiayin; Budoff, Matthew Jay; Lu, Bin

2016-01-01

Surveys that describe the utilization of cardiac CT are available for the United States, Germany, and Taiwan, but not mainland China. To analyze the clinical utilization of cardiac CT in mainland China. A 25-item questionnaire was created and 240 tertiary hospitals were randomly selected to participate. Survey data were collected and confirmed by email as well as phone interviews. In total, 237 (99%) hospitals consented to this survey, but 85 were excluded because of lack of cardiac CT patient volume or advanced technology. Finally, 152 (64%) questionnaires were available for analysis. Median patient volume was 1,037 patients (range: 150-8,072) annually. The most common clinical indications for coronary CT angiography were exclusion of coronary artery disease in patients with low to intermediate pretest likelihood, asymptomatic individuals with cardiovascular risk factors, and follow-up after coronary bypass grafting. The median heart rate threshold for beta blocker administration was >70 beats/min; most centers (86%) used sublingual nitroglycerin. Prospectively ECG triggered acquisition was the predominant technique in 44% of hospitals. Most (59%) providers adjusted the tube current to the body mass, but few (16%) adjusted the contrast injection rate. Per case, the mean examination duration was 14.2 min; post-processing time 13.6 min; and reporting time 18.0 min. Cardiac CT is widely established in clinical practice in mainland China but there is a need for more uniform standards regarding performance and clinical utilization. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Endothelial function across an oral contraceptive cycle in women using levonorgestrel and ethinyl estradiol.

PubMed

Torgrimson, Britta N; Meendering, Jessica R; Kaplan, Paul F; Minson, Christopher T

2007-06-01

Oral contraceptive pills (OCPs) are a popular contraception method. Currently, lower-dose ethinyl estradiol formulations are most commonly prescribed, although they have been linked to increased arterial vascular risk. The aim of this study was to investigate endothelial function in healthy young women using lower-dose ethinyl estradiol OCPs. We examined flow-mediated, endothelium-dependent and nitroglycerin-mediated, endothelium-independent vasodilation of the brachial artery, comparing two doses of ethinyl estradiol/levonorgestrel OCPs in 15 healthy young women on two study days: once during the active phase and once during the placebo phase of an OCP cycle. Group low dose (LD) (n=7) active pills contained 150 microg levonorgestrel/30 microg ethinyl estradiol versus Group very low dose (VLD) (n=8) with 100 microg levonorgestrel/20 microg ethinyl estradiol. Endothelium-dependent vasodilation was lower during the active phase in Group VLD (5.33 +/- 1.77% vs. 7.23 +/- 2.60%; P=0.024). This phase difference was not observed in Group LD (8.00 +/- 0.970% vs. 7.61 +/- 1.07%; P=0.647). Endothelium-independent vasodilation did not differ between phases in either group. Finally, we measured endothelium-dependent vasodilation in two additional women who received 10 microg of unopposed ethinyl estradiol. Endothelium-dependent vasodilation was increased by unopposed ethinyl estradiol compared with the placebo phase (10.88 +/- 2.34% vs. 6.97 +/- 1.83%). These results suggest that levonorgestrel may antagonize the activity of ethinyl estradiol. Thus both the progestin type and estradiol dose need to be considered when assessing arterial vascular risk of OCP use in women.

High-efficiency headspace sampling of volatile organic compounds in explosives using capillary microextraction of volatiles (CMV) coupled to gas chromatography-mass spectrometry (GC-MS).

PubMed

Fan, Wen; Almirall, José

2014-03-01

A novel geometry configuration based on sorbent-coated glass microfibers packed within a glass capillary is used to sample volatile organic compounds, dynamically, in the headspace of an open system or in a partially open system to achieve quantitative extraction of the available volatiles of explosives with negligible breakthrough. Air is sampled through the newly developed sorbent-packed 2 cm long, 2 mm diameter capillary microextraction of volatiles (CMV) and subsequently introduced into a commercially available thermal desorption probe fitted directly into a GC injection port. A sorbent coating surface area of ∼5 × 10(-2) m(2) or 5,000 times greater than that of a single solid-phase microextraction (SPME) fiber allows for fast (30 s), flow-through sampling of relatively large volumes using sampling flow rates of ∼1.5 L/min. A direct comparison of the new CMV extraction to a static (equilibrium) SPME extraction of the same headspace sample yields a 30 times improvement in sensitivity for the CMV when sampling nitroglycerine (NG), 2,4-dinitrotoluene (2,4-DNT), and diphenylamine (DPA) in a mixture containing a total mass of 500 ng of each analyte, when spiked into a liter-volume container. Calibration curves were established for all compounds studied, and the recovery was determined to be ∼1 % or better after only 1 min of sampling time. Quantitative analysis is also possible using this extraction technique when the sampling temperature, flow rate, and time are kept constant between calibration curves and the sample.

Hydralazine and Organic Nitrates Restore Impaired Excitation-Contraction Coupling by Reducing Calcium Leak Associated with Nitroso-Redox Imbalance*

PubMed Central

Dulce, Raul A.; Yiginer, Omer; Gonzalez, Daniel R.; Goss, Garrett; Feng, Ning; Zheng, Meizi; Hare, Joshua M.

2013-01-01

Although the combined use of hydralazine and isosorbide dinitrate confers important clinical benefits in patients with heart failure, the underlying mechanism of action is still controversial. We used two models of nitroso-redox imbalance, neuronal NO synthase-deficient (NOS1−/−) mice and spontaneously hypertensive heart failure rats, to test the hypothesis that hydralazine (HYD) alone or in combination with nitroglycerin (NTG) or isosorbide dinitrate restores Ca2+ cycling and contractile performance and controls superoxide production in isolated cardiomyocytes. The response to increased pacing frequency was depressed in NOS1−/− compared with wild type myocytes. Both sarcomere length shortening and intracellular Ca2+ transient (Δ[Ca2+]i) responses in NOS1−/− cardiomyocytes were augmented by HYD in a dose-dependent manner. NTG alone did not affect myocyte shortening but reduced Δ[Ca2+]i across the range of pacing frequencies and increased myofilament Ca2+ sensitivity thereby enhancing contractile efficiency. Similar results were seen in failing myocytes from the heart failure rat model. HYD alone or in combination with NTG reduced sarcoplasmic reticulum (SR) leak, improved SR Ca2+ reuptake, and restored SR Ca2+ content. HYD and NTG at low concentrations (1 μm), scavenged superoxide in isolated cardiomyocytes, whereas in cardiac homogenates, NTG inhibited xanthine oxidoreductase activity and scavenged NADPH oxidase-dependent superoxide more efficiently than HYD. Together, these results revealed that by reducing SR Ca2+ leak, HYD improves Ca2+ cycling and contractility impaired by nitroso-redox imbalance, and NTG enhanced contractile efficiency, restoring cardiac excitation-contraction coupling. PMID:23319593

Hypertensive emergencies remain a clinical problem and are associated with high mortality.

PubMed

Roubsanthisuk, Weranuj; Wongsurin, Unticha; Buranakitjaroen, Peera

2010-01-01

We suspect that hypertensive emergencies remain a clinical problem and data on their long-term prognosis are lacking. This study was conducted in order to determine the frequency, management, and outcome of hypertensive emergencies in this era, in which hypertension treatment is more effective than in the past. We reviewed the medical records of patients with hypertensive emergencies admitted to the medical wards of Siriraj Hospital in 2003 and collected data on their characteristic, management, investigations, and follow-ups through 31 December 2007. There were 184 patients included. Hypertension has been previously diagnosed in 89% of cases. Nearly half also had diabetes mellitus and around a quarter had chronic kidney failure. Mean +/- SD of blood pressure at presentation was 205.96 +/- 21.36/114.60 +/- 20.59 mmHg. Cardiac complications and stroke accounted for 71% and 23% of all target organ damage, respectively. Intravenous nitroglycerine and furosemide were most frequently prescribed. Additional investigations to search for the causes of hypertension were performed in only 55 cases. The average hospital stay was 9.8 days. The in-hospital mortality rate was 15%. Some 26% of patients were lost to follow-up and another 20% died later. Only 19% of patients had regular follow-ups until the end of 2007 and remained on an average of 2.4 antihypertensive drugs. Hypertensive emergencies are usually found in patients with a history of hypertension and diabetes mellitus or kidney failure. Recommended investigations usually failed to identify the cause of hypertension. The mortality rate of these patients was extremely high while their adherence to treatment was extremely poor.

Neutral endopeptidase modulates substance P-induced vasodilation in vivo.

PubMed

Gao, X P; Rubinstein, I

1995-02-01

The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44-70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1-9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.

Human pharmaceutical products in the environment - the "problem" in perspective.

PubMed

Taylor, David; Senac, Thomas

2014-11-01

Concerns about the potential for significant environmental impact from residues of human pharmaceuticals emerged at the beginning of the 21st century. Since then there has been an exponential rise in the number of publications and conferences on this "problem". However, this intense focus on human pharmaceuticals is misplaced. Pharmaceuticals do not consist of a coherent group of substances with similar chemical, structural, biological or toxicological properties. Pharmaceuticals are only identifiable from their use: in other words substances can be divided into two classes, those that are used as pharmaceuticals and those for which a possible pharmaceutical use has not yet been discovered. For example, nitro-glycerine, Warfarin and dimethyl fumarate, initially sold respectively as an explosive, a rodenticide and a mould inhibitor have subsequently all been used as pharmaceuticals. As analytical science advances, an increasing range of environmental contaminants, including pharmaceuticals, is being identified at sub μgL(-1) concentrations. Although, human and environmental exposure to these contaminants will be low, all of them need to be subjected to risk assessment on a case by case basis. Many of these substances, including human pharmaceuticals, may have little, if any, impact on human health or the environment, however for some substances there may be a significant risk and in these cases appropriate action should be taken. However considering all human pharmaceuticals as a special case, isolated from the wider range of emerging contaminants, is scientifically unjustifiable and diverts resources away from the consideration of other substances that may be of considerably more significance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Salvianolate injection in the treatment of unstable angina pectoris

PubMed Central

Zhang, Dan; Wu, Jiarui; Liu, Shi; Zhang, Xiaomeng; Zhang, Bing

2016-01-01

Abstract Background: To systematically evaluate the clinical efficacy and safety of Salvianolate injection in the treatment of unstable angina pectoris (UAP). Methods: Using literature databases, we conducted a thorough and systematic retrieval of randomized controlled trials (RCTs) that using Salvianolate injection for treating UAP. The Cochrane Risk of Bias Assessment Tool was used to evaluate the methodological quality of the RCTs, and then the data were extracted and meta-analyzed by RevMan5.2 software. Results: A total of 22 RCTs with 2050 participants were included. The meta-analysis indicated that the combined use of Salvianolate injection and western medicine (WM) in the treatment of UAP can achieve a superior effect in angina pectoris total effective rate (risk ratio [RR] = 1.22, 95% confidence interval [CI] (1.17, 1.27), Z = 10.15, P < 0.00001], and the total effectiveness rate of electrocardiogram [RR = 1.26, 95% CI (1.19,1.34), Z = 7.77, P < 0.00001]. In addition, Salvianolate injection can improve the nitroglycerin withdrawal rate and the serum level of NO, decrease high-sensitivity C-reactive protein. Adverse drug reactions (ADRs) or adverse drug events (ADEs) were reported in 6 RCTs involving 15 cases; however, there were no serious ADRs/ADEs. Conclusion: Based on the systematic review, the combined use of Salvianolate injection and WM in the treatment of UAP can achieve a better effect; however, there was no definitive conclusion about its safety. More the large-sample and multicenter RCTs are needed to support its clinical usage. PMID:28002341

Nitrates and Nitrites in the Treatment of Ischemic Cardiac Disease

PubMed Central

Nossaman, Vaughn E.; Nossaman, Bobby D.; Kadowitz, Philip J.

2010-01-01

The organic nitrite, amyl of nitrite, was initially used as a therapeutic agent in the treatment of angina pectoris in 1867, but was replaced over a decade later by the organic nitrate, nitroglycerin (NTG), due to the ease of administration and longer duration of action. The administration of organic nitrate esters, such as NTG, continues to be used in the treatment of angina pectoris and heart failure during the birth of modern pharmacology. The clinical effectiveness is due to vasodilator activity in large veins and arteries through an as yet unidentified method of delivering nitric oxide (NO), or a NO-like compound to vascular smooth muscle cells. The major drawback with NTG administration is the rapid development of tolerance; and with amyl of nitrite, the duration and route of administration. Although amyl of nitrite are no longer used in the treatments of hypertension or ischemic heart disease, the nitrite anion has recently been discovered to possess novel pharmacologic actions such as modulating hypoxic vasodilation and providing cytoprotection in ischemia-reperfusion injury. Although the actions of these two similar chemical classes (nitrites and organic nitrates) have often been considered to be alike, we still do not understand their mechanism of action. However, the recent discovery that the nitrite anion, derived from either sodium nitrite or an intermediate NTG form, may act as a storage form for NO and provides support for investigating the use of these agents in the treatment of ischemic cardiovascular states. We review what is presently known about the use of nitrites and nitrates, the potential uses of these agents, and their mechanisms of action. PMID:20539102

A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena.

PubMed

Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

2009-09-01

The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes.

Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals.

PubMed

Choi, Eun-Yong; Lee, Hansongyi; Woo, Jong Shin; Jang, Hyun Hee; Hwang, Seung Joon; Kim, Hyun Soo; Kim, Woo-Sik; Kim, Young-Seol; Choue, Ryowon; Cha, Yong-Jun; Yim, Jung-Eun; Kim, Weon

2015-09-01

Acute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. This was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. Baseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. Medium-term administration of OPE an improvement in FMD and circulating EPCs. Copyright © 2015 Elsevier Inc. All rights reserved.

Nimodipine-induced hypotension but not nitroglycerin-induced hypotension preserves long- and short-term memory in adult mice.

PubMed

Haile, Michael; Galoyan, Samuel; Li, Yong-Sheng; Cohen, Barry H; Quartermain, David; Blanck, Thomas; Bekker, Alex

2012-05-01

Acute hypotension may be implicated in cognitive dysfunction. L-type calcium channel blockers in the setting of hypoxia are protective of learning and memory. We tested the hypothesis that hypotension induced by nimodipine (NIMO) and nicardipine (NICA) would be protective of long- and short-term memory compared to hypotension induced by nitroglycerin (NTG). Forty Swiss-Webster mice (30 to 35 g, 6 to 8 weeks) were randomized into 4 groups for i.p. injection immediately after passive avoidance (PA) learning on day 0: (1) NTG (30 mg/kg); (2) NICA (40 mg/kg); (3) NIMO (40 mg/kg); and (4) saline. PA training latencies (seconds) were recorded for entry from a suspended platform into a Plexiglas tube where a shock (0.3 mA; 2-second duration) was automatically delivered. On day 2 latencies were recorded during a testing trial during which no shock was delivered. Latencies >900 seconds were assigned this value. Lower testing latency is indicative of an impairment of long-term associative memory. Forty-nine additional mice were randomized into similar groups for object recognition testing (ORT) and given i.p. injections on day 0. ORT measures short-term memory by exploiting the tendency of mice to prefer novel objects where a familiar object is present. On day 5 during training, 2 identical objects were placed in a circular arena and mice explored both for 15 minutes. A testing trial was conducted 1 hour later for 3 minutes after a novel object replaced a familiar one. Mice with intact memory spend about 65% of the time exploring the novel object. Mice with impaired memory devote equal time to each object. Recognition index (RI) is defined as the ratio of time spent exploring the novel object to time spent exploring both objects was the measure of memory. Mean arterial blood pressure (MAP), cerebral bloodflow, and body and brain oxygenation (PO(2)) studies were done in separate groups of mice to determine the dosages for matched degrees of hypotension and the physiological profile of each treatment. The median PA latencies for the different conditions were as follows: NTG (219.5 ± 93.5 second semi-interquartile range [SIQR]), NICA (372.5 ± 75.5 second SIQR), NIMO (540 ± 200 second SIQR) and saline (804 ± 257.5 second SIQR). Rank methods were used to analyze the PA latencies for significant differences. NTG latency was significantly shorter than NIMO latency (P = 0.012) and saline latency (P = 0.006), but not NICA latency (P = 0.126). ORT RI values showed a similar pattern. We found that NTG RI (47.2 ± 5.9% SEM) was different from NIMO RI (60.2 ± 4.6% SEM, P = 0.031) and different from saline RI (66.9 + 3.7% SEM, P = 0.006). Physiological experiments showed that MAP decreased to 45 to 50 mm Hg in all animals who became minimally responsive to external stimuli within 10 to 15 minutes of injection. Intergroup differences for MAP, body and brain oxygenation, and cerebral bloodflow were not statistically significant. Acute hypotension induced by NIMO was protective of 2 categories of memory formation relevant to the clinical posttreatment period. Both immediate long-term associative memory consolidation as measured by the PA learning paradigm and delayed short-term working memory function as measured by the ORT paradigm were significantly improved compared to matched levels of hypotension induced by NTG. These results indicate the utility of further investigation of l-type calcium channel blockers as a potential means of preserving cognition in the setting of hypotensive and low flow states.

Combustion characteristics of SMX and SMX based propellants

NASA Astrophysics Data System (ADS)

Reese, David A.

This work investigates the combustion of the new solid nitrate ester 2,3-hydroxymethyl-2,3-dinitro-1,4-butanediol tetranitrate (SMX, C6H 8N6O16). SMX was synthesized for the first time in 2008. It has a melting point of 85 °C and oxygen balance of 0% to CO 2, allowing it to be used as an energetic additive or oxidizer in solid propellants. In addition to its neat combustion characteristics, this work also explores the use of SMX as a potential replacement for nitroglycerin (NG) in double base gun propellants and as a replacement for ammonium perchlorate in composite rocket propellants. The physical properties, sensitivity characteristics, and combustion behaviors of neat SMX were investigated. Its combustion is stable at pressures of up to at least 27.5 MPa (n = 0.81). The observed flame structure is nearly identical to that of other double base propellant ingredients, with a primary flame attached at the surface, a thick isothermal dark zone, and a luminous secondary flame wherein final recombination reactions occur. As a result, the burning rate and primary flame structure can be modeled using existing one-dimensional steady state techniques. A zero gas-phase activation energy approximation results in a good fit between modeled and observed behavior. Additionally, SMX was considered as a replacement for nitroglycerin in a double base propellant. Thermochemical calculations indicate improved performance when compared with the common double base propellant JA2 at SMX loadings above 40 wt-%. Also, since SMX is a room temperature solid, migration may be avoided. Like other nitrate esters, SMX is susceptible to decomposition over long-term storage due to the presence of excess acid in the crystals; the addition of stabilizers (e.g., derivatives of urea) during synthesis should be sufficient to prevent this. the addition of Both unplasticized and plasticized propellants were formulated. Thermal analysis of unplasticized propellant showed a distinct melt-recrystallization curve, which indicates that a solid phase solution is being formed between SMX and NC, and that SMX would not act as plasticizer. Analysis of propellant prepared with diethyleneglycol dinitrate (DEGDN) plasticizer indicates that the SMX is likely dissolved in the DEGDN. The plasticized material also showed similar hardness and modulus to JA2. However, both plasticized and unplasticized propellants exhibited deconsolidated burning at elevated pressures due to the high modulus of the propellant. Increased amounts of plasticizer or improved processing of the nitrocellulose should be investigated to remedy this issue. Safety characterization showed that sensitivity of the plasticized propellant is similar to JA2. In short, replacing NG with SMX results in a new family of propellants with acceptable safety characteristics and which may also offer improved theoretical performance. Finally, composite propellants based on SMX were theoretically and experimentally examined and compared to formulations based on ammonium perchlorate (AP). Thermochemical equilibrium calculations show that aluminized SMX-based formulations can achieve theoretical sea level specific impulse values upwards of 260 s-- slightly lower than an AP-based composite. Both ignition sensitivity (tested via drop weight impact, electro-static discharge, and BAM friction) and physical properties (hardness and thermal properties) are comparable to those of the AP-based formulations. However, the SMX-based formulation could be detonated using a high explosive donor charge in contact with the propellant, as do other low smoke propellants. Differential scanning calorimetry of the SMX-based propellant indicated an exotherm onset of 140 °C, which corresponds to the known decomposition temperature of SMX. The propellant has a high burning rate of 1.57 cm/s at 6.89 MPa, with a pressure exponent of 0.85. This high pressure sensitivity might be addressed using various energetic and/or stabilizing additives. With high density and performance, smokeless combustion products, and stable combustion, SMX appears to be a viable replacement for existing energetic ingredients in a wide variety of propellant, explosive, and pyrotechnic applications.

Heterogeneity in relaxation of different sized porcine coronary arteries to nitrovasodilators: role of PKG and MYPT1.

PubMed

Ying, Lei; Xu, Xiaojian; Liu, Juan; Dou, Dou; Yu, Xiaoxing; Ye, Liping; He, Qiong; Gao, Yuansheng

2012-02-01

The present study was to determine the role of the type I isoform of cGMP-dependent protein kinase (PKG I) and its downstream effector myosin phosphatase target subunit 1 (MYPT1) in the responses of different sized coronary arteries to nitrovasodilators. Relaxations of isolated porcine coronary arteries were determined by isometric tension recording technique. Protein levels of PKG I and its effectors were analyzed by Western blotting. The activities of PKG I and MYPT1 were studied by analyzing phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and MYPT1, respectively. Nitroglycerin, DETA NONOate, and 8-Br-cGMP caused greater relaxations in large than in small coronary arteries. Relaxations were attenuated to a greater extent by Rp-8-Br-PET-cGMPS (a PKG inhibitor) in large vs. small arteries. The expressions of PKG I and MYPT1 in large arteries were more abundant than in small arteries. DETA NONOate stimulated phosphorylation of VASP at Ser239 and inhibited phosphorylation of MYPT1 at Thr853 to a greater extent in large than in small arteries. A suppressed phosphorylation of MYPT1 at Thr853 was caused by 8-Br-cGMP in large but not small arteries, which was inhibited by Rp-8-Br-PET-cGMPS. These results suggest that the greater responsiveness of large coronary arteries to nitrovasodilators result in part from greater activities of PKG I and MYPT1. Dysfunction in nitric oxide signaling is implicated in the vulnerability of large coronary arteries to certain disorders such as atherosclerosis and spasm. Augmentation of PKG I-MYPT1 signaling may be of therapeutic benefit for combating these events.

Impact of vasomotion type on prognosis of coronary artery spasm induced by acetylcholine provocation test of left coronary artery.

PubMed

Lee, Eun Mi; Choi, Man Ho; Seo, Hong Seog; Kim, Hyun Ki; Kim, Nam-Ho; Choi, Cheol Ung; Kim, Jin Won; Lim, Hong Euy; Kim, Eung Ju; Rha, Seung-Woon; Park, Chang Gyu; Oh, Dong Joo

2017-02-01

The impact of vasomotion types on long-term clinical outcomes in patients with coronary artery spasm (CAS) induced by the acetylcholine provocation test (ACH-test) remains unclear. We evaluated 4644 consecutive patients with typical resting chest pain (CP), but no angiographically significant coronary artery lesion (<50% stenosis), who underwent an ACH-test. According to their vasomotor response, patients were categorized into four types: normal vasomotion (no CP, no ischemic electrocardiographic changes, and no vasoconstriction), microvascular spasm (CP with <75% vasoconstriction but with CP relief after nitroglycerin infusion), epicardial spasm (CP with ≥75% vasoconstriction), and ACH-test inconclusive (vasoconstriction and/or electrocardiographic changes, but no CP). We investigated CP recurrence requiring follow-up angiography and major adverse cardiovascular events (MACEs) during 5 years. CP recurred in 7.9% of patients and was more frequent in abnormal vasomotion types (normal vasomotion, microvascular spasm, epicardial spasm, and inconclusive type: 5.4%, 9.8%, 10.9%, and 8.2%, respectively, log-rank p = 0.009). In multivariate analysis adjusted for medication use after the ACH-test, vasomotion subtype was not an independent predictor, whereas male sex, fixed lesion on baseline angiography, and medications including calcium channel blockers (CCBs), nitrates, and statins were independent positive predictors for recurrent CP. Alcohol consumption at the initial interview was a negative predictor. MACEs were observed in 1.6%, and the incidence was similar among subtypes (p = 0.421). Recurrent CP and long-term outcomes are independent of vasomotion subtypes, but long-term use of CCBs, nitrates, and statins is a significant predictor for recurrent CP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Massage Therapy Restores Peripheral Vascular Function following Exertion

PubMed Central

Franklin, Nina C.; Ali, Mohamed M.; Robinson, Austin T.; Norkeviciute, Edita; Phillips, Shane A.

2014-01-01

Objective To determine if lower extremity exercise-induced muscle injury (EMI) reduces vascular endothelial function of the upper extremity and if massage therapy (MT) improves peripheral vascular function after EMI. Design Randomized, blinded trial with evaluations at 90 minutes, 24 hours, 48 hours, and 72 hours. Setting Clinical research center at an academic medical center and laboratory Participants Thirty-six sedentary young adults were randomly assigned to one of three groups: 1) EMI + MT (n=15; mean age ± standard error (SE): 26.6±0.3), 2) EMI only (n=10; mean age ± SE: 23.6±0.4), and 3) MT only (n=11; mean age ± SE: 25.5 ± 0.4). Intervention Participants were assigned to either EMI only (a single bout of bilateral, eccentric leg-press exercise), MT only (30-minute lower extremity massage using Swedish technique), or EMI + MT. Main outcome measures Brachial artery flow-mediated dilation (FMD) was determined by ultrasound at each time point. Nitroglycerin-induced dilation was also assessed (NTG; 0.4 mg). Results Brachial FMD increased from baseline in the EMI + MT group and the MT only group (7.38±0.18 to 9.02±0.28%, p<0.05 and 7.77±0.25 to 10.20±0.22%, p < 0.05, respectively) at 90 minutes remaining elevated until 72 hrs. In the EMI only group FMD was reduced from baseline at 24 and 48 hrs (7.78±0.14 to 6.75±0.11%, p<0.05 and 6.53±0.11, p<0.05, respectively) returning to baseline after 72 hrs. Dilations to NTG were similar over time. Conclusions Our results suggest that MT attenuates impairment of upper extremity endothelial function resulting from lower extremity EMI in sedentary young adults. PMID:24583315

Long-term effects of bariatric surgery on peripheral endothelial function and coronary microvascular function.

PubMed

Tarzia, Pierpaolo; Lanza, Gaetano A; Sestito, Alfonso; Villano, Angelo; Russo, Giulio; Figliozzi, Stefano; Lamendola, Priscilla; De Vita, Antonio; Crea, Filippo

We previously demonstrated that bariatric surgery (BS) leads to a short-term significant improvement of endothelial function and coronary microvascular function. In this study we assessed whether BS maintains its beneficial effect at long-term follow up. We studied 19 morbidly obese patients (age 43±9years, 12 women) without any evidence of cardiovascular disease who underwent BS. Patients were studied before BS, at 3 months and at 4.0±1.5years follow up. Peripheral vascular function was assessed by flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), i.e., brachial artery diameter changes in response to post-ischemic forearm hyperhaemia and to nitroglycerin administration, respectively. Coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to intravenous adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery. Together with improvement of anthropometric and metabolic profile, at long-term follow-up patients showed a significant improvement of FMD (6.43±2.88 vs. 8.21±1.73%, p=0.018), and CBF response to both adenosine (1.73±0.48 vs. 2.58±0.54; p<0.01) and CPT (1.43±0.30 vs. 2.23±0.48; p<0.01), compared to basal values. No differences in vascular end-points were shown at 3-month and 4-year follow-up after BS. Our data show that, in morbidly obese patients, BS exerts beneficial and long lasting effects on peripheral endothelial function and on coronary microvascular dilator function. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

The enhancement mechanism of wine-processed Radix Scutellaria on NTG-induced migraine rats.

PubMed

Cui, Cheng-Long; He, Xin; Dong, Cui-Lan; Song, Zi-Jing; Ji, Jun; Wang, Xue; Wang, Ling; Wang, Jiao-Ying; Du, Wen-Juan; Wang, Chong-Zhi; Yuan, Chun-Su; Guo, Chang-Run; Zhang, Chun-Feng

2017-07-01

To elucidate the increasing dissolution and enhancement mechanism of wine-processed Radix Scutellaria (RS) by fractal theory in nitroglycerin (NTG)-induced migraine rats. We prepared three RS from the process with 10% (S1), 15% (S2), 20% (S3) (v/m) rice wine. Mercury intrusion porosimetry and scanning electron microscope were employed to explore the internal structure of RS and the components dissolution of RS was analyzed by HPLC. Rats were randomly allocated into following groups and orally given different solutions for 10days: normal group (NOR, normal saline), model group (MOD, normal saline), Tianshu capsule group (TSC, 0.425mg/kg), ibuprofen group (IBU, 0.0821mg/kg), crude RS group (CRU, 1.04mg/kg) and wine-processed RS group (WP, 1.04mg/kg) followed by bolus subcutaneously injection of NTG (10mg/kg) to induce migraine model except NOR. Biochemical indexes (nitric oxide-NO, calcitonin-gene-related peptide-CGRP, and endothelin-ET) and c-fos positive cells were measured with commercial kits and immunohistochemical method, separately. Total surface area significantly increased in wine-processed RS (p<0.05) while fractal dimension markedly decreased (p<0.05) compared with crude RS. Additionally, S3 owned the highest increase of dissolution including the percentage increase of total extract, total flavonoids and main compounds (all p<0.05 vs S1 and S2). Pharmacodynamic data showed c-fos positive cells significantly decreased (p<0.05) in WP compared with MOD and the level of NO, CGRP, ET in WP was better than that of CRU. Wine-processed RS could be a promising candidate medicine for migraine treatment due to its increased component dissolution. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress.

PubMed

Daiber, Andreas; Münzel, Thomas

2015-10-10

Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3',-5'-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed.

Exploration of the rapid effects of personal fine particulate matter exposure on arterial hemodynamics and vascular function during the same day.

PubMed

Brook, Robert D; Shin, Hwashin H; Bard, Robert L; Burnett, Richard T; Vette, Alan; Croghan, Carry; Thornburg, Jonathan; Rodes, Charles; Williams, Ron

2011-05-01

Levels of fine particulate matter [≤ 2.5 μm in aerodynamic diameter (PM(2.5))] are associated with alterations in arterial hemodynamics and vascular function. However, the characteristics of the same-day exposure-response relationships remain unclear. We aimed to explore the effects of personal PM(2.5) exposures within the preceding 24 hr on blood pressure (BP), heart rate (HR), brachial artery diameter (BAD), endothelial function [flow-mediated dilatation (FMD)], and nitroglycerin-mediated dilatation (NMD). Fifty-one nonsmoking subjects had up to 5 consecutive days of 24-hr personal PM(2.5) monitoring and daily cardiovascular (CV) measurements during summer and/or winter periods. The associations between integrated hour-long total personal PM(2.5) exposure (TPE) levels (continuous nephelometry among compliant subjects with low secondhand tobacco smoke exposures; n = 30) with the CV outcomes were assessed over a 24-hr period by linear mixed models. We observed the strongest associations (and smallest estimation errors) between HR and TPE recorded 1-10 hr before CV measurements. The associations were not pronounced for the other time lags (11-24 hr). The associations between TPE and FMD or BAD did not show as clear a temporal pattern. However, we found some suggestion of a negative association with FMD and a positive association with BAD related to TPE just before measurement (0-2 hr). Brief elevations in ambient TPE levels encountered during routine daily activity were associated with small increases in HR and trends toward conduit arterial vasodilatation and endothelial dysfunction within a few hours of exposure. These responses could reflect acute PM(2.5)-induced autonomic imbalance and may factor in the associated rapid increase in CV risk among susceptible individuals.

[Extracorporeal cardiac shock wave therapy for treatment of coronary artery disease].

PubMed

Wang, Yu; Guo, Tao; Cai, Hong-Yan; Ma, Tie-Kun; Tao, Si-Ming; Chen, Ming-Qing; Gu, Yun; Pan, Jia-Hua; Xiao, Jian-Ming; Zhao, Ling; Yang, Xi-Yun; Yang, Chao

2010-08-01

To evaluate the feasibility and efficiency of extracorporeal cardiac shock wave therapy (CSWT) for treatment of coronary artery disease. Twenty-five patients with 1 - 16 years history of chronic angina pectoris underwent the CSWT. Before and after the treatment, low-dose Dobutamine stress echocardiography and (99)Tc(m)-MIBI myocardial perfusion SPECT were applied to locate the ischemic segments, detect the viable myocardium and evaluate the effect of CSWT. Under the guidance of echocardiography, CSWT was applied in R-wave-triggered manner with low energy (0.09 mJ/mm(2)) at 200 shoots/spot for 9 spots (-1-0-+1 combination). Patients were divided group A and group B. Sixteen patients in group A were applied 9 sessions on 29 segments within 3 month and nine patients in group B were applied 9 sessions on 13 segments within 1 month. Ten chronic angina pectoris patients receiving standard medication served as controls. All patients completed the 9 sessions without procedural complications or adverse effects. CSWT significantly improved symptoms as evaluated by NYHA, Canadian Cardiovascular Society (CCS) class sores, Seattle angina questionnaire (SAQ), 6-min walk and the use of nitroglycerin (P < 0.05). CSWT also improved myocardial perfusion and regional myocardium function as evaluated by rest SPECT and stress peak systolic strain rate (PSSR) (P < 0.01). Myocardial perfusion improvement was more significant in group A compared with group B (1.21 ± 0.86 vs. 0.83 ± 0.80, P < 0.01). All parameters remained unchanged in control group during follow up. These preliminary results indicate that CSWT is safe and effective on ameliorating anginal symptoms for chronic angina pectoris patients.

Emergency and urgent care capacity in a resource-limited setting: an assessment of health facilities in western Kenya

PubMed Central

Burke, Thomas F; Hines, Rosemary; Ahn, Roy; Walters, Michelle; Young, David; Anderson, Rachel Eleanor; Tom, Sabrina M; Clark, Rachel; Obita, Walter; Nelson, Brett D

2014-01-01

Objective Injuries, trauma and non-communicable diseases are responsible for a rising proportion of death and disability in low-income and middle-income countries. Delivering effective emergency and urgent healthcare for these and other conditions in resource-limited settings is challenging. In this study, we sought to examine and characterise emergency and urgent care capacity in a resource-limited setting. Methods We conducted an assessment within all 30 primary and secondary hospitals and within a stratified random sampling of 30 dispensaries and health centres in western Kenya. The key informants were the most senior facility healthcare provider and manager available. Emergency physician researchers utilised a semistructured assessment tool, and data were analysed using descriptive statistics and thematic coding. Results No lower level facilities and 30% of higher level facilities reported having a defined, organised approach to trauma. 43% of higher level facilities had access to an anaesthetist. The majority of lower level facilities had suture and wound care supplies and gloves but typically lacked other basic trauma supplies. For cardiac care, 50% of higher level facilities had morphine, but a minority had functioning ECG, sublingual nitroglycerine or a defibrillator. Only 20% of lower level facilities had glucometers, and only 33% of higher level facilities could care for diabetic emergencies. No facilities had sepsis clinical guidelines. Conclusions Large gaps in essential emergency care capabilities were identified at all facility levels in western Kenya. There are great opportunities for a universally deployed basic emergency care package, an advanced emergency care package and facility designation scheme, and a reliable prehospital care transportation and communications system in resource-limited settings. PMID:25260371

Brachial artery endothelial function is stable across a menstrual and oral contraceptive pill cycle, but lower in premenopausal women than age-matched men.

PubMed

Shenouda, Ninette; Priest, Stacey E; Rizzuto, Vanessa I; MacDonald, Maureen J

2018-05-04

Sex hormone concentrations differ between men, premenopausal women with natural menstrual cycles (NAT), and premenopausal women using oral contraceptive pills (OCP), as well as across menstrual or OCP phases. This study sought to investigate how differences in sex hormones, particularly estradiol, between men and women and across cycle phases, may influence brachial artery endothelial function. Fifty-three healthy adults (22{plus minus}3 yrs; 20 men, 15 NAT, 18 second, third or fourth generation OCP) underwent assessments of sex hormones and endothelial (flow-mediated dilation test, FMD) and smooth muscle (nitroglycerin test, NTG) function. Men were tested three times at one-week intervals, and women were tested three times throughout a single menstrual or OCP cycle (NAT: menstrual, mid-follicular, luteal; OCP: placebo/no pill, 'early' and 'late' active pill). Endogenous estradiol concentration was comparable between men and women in their NAT menstrual or OCP placebo phase (p=0.36) but increased throughout a NAT cycle (p<0.001). Allometrically scaled FMD did not change across a NAT or OCP cycle but was lower in both groups of women than men (p=0.005), whereas scaled NTG was lower only in NAT women (p=0.001). Changes in estradiol across a NAT cycle were not associated with changes in relative FMD (r2=0.01, p=0.62) or NTG (r2=0.09, p=0.13). Duration of OCP use was negatively associated with the average relative FMD for second generation OCP users only (r=-0.65, p=0.04). Our findings suggest that brachial endothelial function is unaffected by cyclic hormonal changes in premenopausal women but may be negatively impacted by longer term use of second generation OCPs.

Altered brainstem auditory evoked potentials in a rat central sensitization model are similar to those in migraine

PubMed Central

Arakaki, Xianghong; Galbraith, Gary; Pikov, Victor; Fonteh, Alfred N.; Harrington, Michael G.

2014-01-01

Migraine symptoms often include auditory discomfort. Nitroglycerin (NTG)-triggered central sensitization (CS) provides a rodent model of migraine, but auditory brainstem pathways have not yet been studied in this example. Our objective was to examine brainstem auditory evoked potentials (BAEPs) in rat CS as a measure of possible auditory abnormalities. We used four subdermal electrodes to record horizontal (h) and vertical (v) dipole channel BAEPs before and after injection of NTG or saline. We measured the peak latencies (PLs), interpeak latencies (IPLs), and amplitudes for detectable waveforms evoked by 8, 16, or 32 KHz auditory stimulation. At 8 KHz stimulation, vertical channel positive PLs of waves 4, 5, and 6 (vP4, vP5, and vP6), and related IPLs from earlier negative or positive peaks (vN1-vP4, vN1-vP5, vN1-vP6; vP3-vP4, vP3-vP6) increased significantly 2 hours after NTG injection compared to the saline group. However, BAEP peak amplitudes at all frequencies, PLs and IPLs from the horizontal channel at all frequencies, and the vertical channel stimulated at 16 and 32 KHz showed no significant/consistent change. For the first time in the rat CS model, we show that BAEP PLs and IPLs ranging from putative bilateral medial superior olivary nuclei (P4) to the more rostral structures such as the medial geniculate body (P6) were prolonged 2 hours after NTG administration. These BAEP alterations could reflect changes in neurotransmitters and/or hypoperfusion in the midbrain. The similarity of our results with previous human studies further validates the rodent CS model for future migraine research. PMID:24680742

Evaluation of Early Atherosclerosis Markers in Patients with Inflammatory Bowel Disease.

PubMed

Üstün, Yusuf; Kilincalp, Serta; Çoban, Şahin; Coşkun, Yusuf; Yüksel, İlhami; Ongun, Aydan; Soykan, İrfan; Bektaş, Mehmet; Törüner, Murat; Çetinkaya, Hülya; Örmeci, Necati

2016-10-24

BACKGROUND The aim of this study was to investigate relationships between early atherosclerosis and inflammatory bowel disease (IBD) using laboratory, functional, and morphological markers of atherosclerosis. MATERIAL AND METHODS In the present prospective single-center study, 96 patients with IBD (58 patients with ulcerative colitis and 36 patients with Crohn's disease) and 65 healthy control subjects were included. The demographic data of each patient and control subject were recorded. The patients with IBD and healthy controls were compared in terms of the carotid intima-media thickness (CIMT), the values of flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD), and the levels of von Willebrand factor antigen (VWF-Ag), D-dimer, and lipoprotein (a). RESULTS There were no significant differences between the IBD patients and controls in terms of age, sex, BMI, systolic and diastolic BPs, serum levels of total cholesterol, low-density lipoprotein, or triglycerides. IBD patients had significantly higher levels of VWF-Ag (156.6±58.9 vs. 104.2±43.3, P<0.001) and D-dimer (337.2±710.8 vs. 175.9±110.9, P<0.001) as compared to the controls. No significant differences were determined between the 2 groups in terms of FMD and NMD values. Although statistically not significant, the CIMT values were higher in the IBD patients than in the controls (0.517±0.141 mm vs. 0.467±0.099 mm, P=0.073). In the correlation analysis, the CIMT was found to be correlated negatively with FMD and positively with high sensitive C-reactive protein, VWF-Ag, and D-dimer. CONCLUSIONS These findings suggest that VWF-Ag and D-dimer can be beneficial early atherosclerosis markers in IBD patients.

Comprehensive assessment of impaired peripheral and coronary artery endothelial functions in smokers using brachial artery ultrasound and oxygen-15-labeled water PET.

PubMed

Ochi, Noriki; Yoshinaga, Keiichiro; Ito, Yoichi M; Tomiyama, Yuuki; Inoue, Mamiko; Nishida, Mutsumi; Manabe, Osamu; Shibuya, Hitoshi; Shimizu, Chikara; Suzuki, Eriko; Fujii, Satoshi; Katoh, Chietsugu; Tamaki, Nagara

2016-10-01

Comprehensive evaluation of endothelium-dependent and endothelium-independent vascular functions in peripheral arteries and coronary arteries in smokers has never been performed previously. Through the use of brachial artery ultrasound and oxygen-15-labeled water positron emission tomography (PET), we sought to investigate peripheral and coronary vascular dysfunctions in smokers. Eight smokers and 10 healthy individuals underwent brachial artery ultrasound at rest, during reactive hyperemia [250mmHg cuff occlusion (flow-mediated dilatation (FMD)], and following sublingual nitroglycerin (NTG) administration. Myocardial blood flow (MBF) was assessed through O-15-labeled water PET at rest, during adenosine triphosphate (ATP) administration, and during a cold pressor test (CPT). Through ultrasound, smokers were shown to have significantly reduced %FMD compared to controls (6.62±2.28% vs. 11.29±2.75%, p=0.0014). As assessed by O-15-labeled water PET, smokers were shown to have a significantly lower CPT response than were controls (21.1±9.5% vs. 50.9±16.9%, p=0.0004). There was no relationship between %FMD and CPT response (r=0.40, p=0.097). Endothelium-independent vascular dilatation was similar for both groups in terms of coronary flow reserve with PET (p=0.19). Smokers tended to have lower %NTG in the brachial artery (p=0.055). Smokers exhibited impaired coronary endothelial function as well as peripheral brachial artery endothelial function. In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in peripheral arteries and coronary arteries. Copyright © 2016. Published by Elsevier Ltd.

Extravasation of Noncytotoxic Drugs: A Review of the Literature.

PubMed

Le, Ann; Patel, Samit

2014-07-01

Extravasation is a potential complication associated with intravenous therapy administration. Inadvertent leakage of medications with vesicant properties can cause severe tissue necrosis, which can lead to devastating long-term consequences. Recognizing potential agents is an essential step in mitigating the risk of extravasation. A literature search was carried out using PubMed with the following key words: extravasation, soft tissue injury, phlebitis, and infiltration, from January 1961 through January 2014. The publications were screened manually and reviewed to identify reports for medications that included synonyms of the International Nonproprietary Name, while excluding antineoplastic agents, radiographic contrast material, investigational or nonmarketed drugs, and animal data, to yield 70 articles. Furthermore, reference citations from publications were also reviewed for relevance and yielded 4 articles. We discovered 232 cases of extravasation involving 37 agents (in order of frequency): phenytoin, parenteral nutrition, calcium gluconate, potassium chloride, calcium chloride, dopamine, dextrose solutions, epinephrine, sodium bicarbonate, nafcillin, propofol, norepinephrine, mannitol, arginine, promethazine, vancomycin, tetracycline, dobutamine, vasopressin, sodium thiopental, acyclovir, amphotericin, ampicillin, cloxacillin, gentamicin, metronidazole, oxacillin, penicillin, amiodarone, albumin, furosemide, lipids, lorazepam, immunoglobulin, morphine, and sodium valproate. Potential properties contributing to extravasation include the following: pH, osmolarity, diluent, vasoactive properties, and inactive ingredients. Antidotes and supportive care agents used in the management of these cases of extravasation include hyaluronidase, phentolamine, terbutaline, topical anesthetics (such as lidocaine and prilocaine cream), topical antimicrobials (such as silver sulfadiazine and chlorhexidine), topical debridement agents (collagenase ointment), topical steroids, and topical vasodilators (nitroglycerin). Data on the management of noncytotoxic extravasations is sparse, consisting primarily of case reports and anecdotal evidence. Fortunately, this adverse outcome is preventable and identification of vesicant agents plays a pivotal role. The intent of this review is to provide a reference identifying noncytotoxic vesicants and the management of extravasations associated with specific agents. © The Author(s) 2014.

Angeli's Salt, a nitroxyl anion donor, reverses endothelin-1 mediated vascular dysfunction in murine aorta.

PubMed

Wynne, Brandi M; Labazi, Hicham; Carneiro, Zidonia N; Tostes, Rita C; Webb, R Clinton

2017-11-05

Nitroglycerin (Gtn) is a treatment for cardiovascular patients due to its vasodilatory actions, but induces tolerance when given chronically. A proposed mechanism is the superoxide (O 2 - )-oxidative stress hypothesis, which suggests that Gtn increases O 2 - production. Nitric oxide (NO) exists in three different redox states; the protonated, reduced state, nitroxyl anion (HNO) is an emerging candidate in vascular regulation. HNO is resistant to scavenging and of particular interest in conditions where high levels of reactive oxygen species (ROS) exist. We hypothesize that treatment with Gtn will exacerbate endothelin 1 (ET-1) induced vascular dysfunction via an increase in ROS, while treatment with Angeli's Salt (AS), an HNO donor, will not. Aorta from mice were isolated and divided into four groups: vehicle, ET-1 [0.1μM, 1μM], ET-1+Gtn [Gtn 1μM] and ET-1+AS [AS 1μM]. Concentration response curves (CRCs) to acetylcholine (ACh) and phenylephrine (Phe) were performed. Aorta incubated with ET-1 (for 20-22h) exhibited a decreased relaxation response to ACh and an increase in Phe-mediated contraction. Aorta incubated with AS exhibited a reversal in ET-1 induced vascular and endothelial dysfunction. ET-1 increased ROS in aortic vascular smooth muscle cells (VSMCs), visualized by dihydroethidium (DHE) staining. AS incubated reduced this ROS generation, yet maintained with Gtn treatment. These data suggest that aorta incubated with the HNO donor, AS, can reverse ET-1 mediated vascular dysfunction, which may be through a decrease or prevention of ROS generation. We propose that HNO may be vasoprotective and that HNO donors studied as a therapeutic option where other organic nitrates are contraindicative. Copyright © 2017 Elsevier B.V. All rights reserved.

Fixed-dose combination of losartan and hydrochlorothiazide significantly improves endothelial function in uncontrolled hypertension by low-dose amlodipine: a randomized study.

PubMed

Takase, Bonpei; Nagata, Masayoshi

2014-12-01

Flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery are well-known indices for evaluating endothelial function (ECF). The blood pressure-lowering effects of the combination of losartan (ARB) and low-dose hydrochlorothiazide (H: ARB-H; ARB, 50 mg and H, 12.5 mg) are useful. The aim of the present study was to examine whether the combination of losartan and low-dose hydrochlorothiazide could improve ECF. To investigate the effect of ARB-H on ECF in patients with uncontrolled hypertension despite the use of amlodipine (2.5 mg daily), we performed a randomized controlled open-labeled study by using the envelope method and assigned 42 patients to either a control (CTRL) group or an ARB-H combination group, both of which received amlodipine 2.5 mg daily during the treatment period. In addition, both the CTRL (n=21, 69±7 years old) and ARB-H groups (n=21, 69±7 years old) received additional behavioral modification. Before and after 8 weeks of therapy, FMD and NMD were measured in both groups using novel FMD equipment (UNEXEF18G). Although baseline FMD was not different between the two groups, post-therapy FMD increased in the ARB-H group (2.97±1.56 to 3.95±1.86%, p<0.05) but did not change significantly in the CTRL group (2.95±1.43 to 3.11±1.27%, NS). No significant change was seen in NMD when comparing baseline and post-therapy values in either group. No treatment complications were observed. A fixed-dose combination of losartan and hydrochlorothiazide enhances ECF, suggesting that this combination might have both anti-hypertensive and anti-atherosclerotic effects in patients with hypertension.

Hemofiltration in ex vivo lung perfusion-a study in experimentally induced pulmonary edema.

PubMed

Nilsson, Tobias; Hansson, Christoffer; Wallinder, Andreas; Malm, Carl-Johan; Silverborn, Martin; Ricksten, Sven-Erik; Dellgren, Göran

2016-02-01

Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight. In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF. After in vivo induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups. In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Treatment of denture-related stomatitis improves endothelial function assessed by flow-mediated vascular dilation.

PubMed

Osmenda, Grzegorz; Maciąg, Joanna; Wilk, Grzegorz; Maciąg, Anna; Nowakowski, Daniel; Loster, Jolanta; Dembowska, Elżbieta; Robertson, Douglas; Guzik, Tomasz; Cześnikiewicz-Guzik, Marta

2017-02-01

The presence of oral inflammation has recently been linked with the pathogenesis of cardiovascular diseases. While numerous studies have described links between periodontitis and endothelial dysfunction, little is known about the influence of denture-related stomatitis (DRS) on cardiovascular risk. Therefore, the aim of this study was to determine whether the treatment of DRS can lead to improvement of the clinical measures of vascular dysfunction. The DRS patients were treated with a local oral antifungal agent for 3 weeks. Blood pressure, flow-mediated dilatation (FMD) and nitroglycerine-mediated vascular dilatation (NMD) were measured during three study visits: before treatment, one day and two months after conclusion of antifungal therapy. Flow-mediated dilatation measurements showed significant improvement of endothelial function 2 months after treatment (FMD median 5%, 95 CI: 3-8.3 vs. 11%, 95% CI: 8.8-14.4; p < 0.01), while there was no difference in control, endothelium-independent vasorelaxations (NMD; median = 15.3%, 95% CI: 10.8-19.3 vs. 12.7%, 95% CI: 10.6-15; p = 0.3). Other cardiovascular parameters such as systolic (median = 125 mm Hg; 95% CI: 116-129 vs. 120 mm Hg, 95% CI: 116-126; p = 0.1) as well as diastolic blood pressure and heart rate (median = 65.5 bpm, 95% CI: 56.7-77.7 vs. 71 bpm, 95% CI: 66.7-75; p = 0.5) did not change during or after the treatment. Treatment of DRS is associated with improvement of endothelial function. Since endothelial dysfunction is known to precede the development of severe cardiovascular disorders such as atherosclerosis and hypertension, patients should be more carefully screened for DRS in general dental practice, and immediate DRS treatment should be advised.

Rapid identification and desorption mechanisms of nitrogen-based explosives by ambient micro-fabricated glow discharge plasma desorption/ionization (MFGDP) mass spectrometry.

PubMed

Tian, CaiYan; Yin, JinWei; Zhao, ZhongJun; Zhang, Yinchenxi; Duan, YiXiang

2017-05-15

A novel technique of micro-fabricated glow discharge plasma desorption/ionization mass spectrometry was investigated for the first time in negative ion mode in this study. Negative ion micro-fabricated glow discharge plasma desorption/ionization mass spectrometry (NI-MFGDP-MS) was successfully applied to identify trace explosives in open air. Six explosives and explosives-related compounds were directly analyzed in seconds with this ion source. The ions of [M-H] - were predominant for 2-methyl-1,3,5-trinitrobenzene (trinitrotoluene, TNT) and 2,4,6-trinitrophenol (picric acid), and [M+NO 3 ] - were dominant ions for 1,3,5-trinitro-perhydro-1,3,5-triazine (cyclonite, RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (octogen, HMX), 1,2,3-trinitroxypropane (nitroglycerin, NG), and pentaerythritol tetranitrate (PETN). The limits of detection (LOD) were from 87.5pgmm -2 to 0.4 fg mm -2 and the relative standard deviation (RSD) ranged between 5.8% and 16.8% for the explosives involved in this study. The reliability of NI-MFGDP-MS was characterized by the analysis of a picric acid-RDX-PETN mixture and a mixture of RDX-pond water. NI-MFGDP-MS and ESI-MS were compared with these explosives and along with collision induced dissociation (CID) experiments. The results showed that electron capture, proton abstraction reaction, nucleophilic attack, ion-molecule attachment, decomposition and anion attachment took place during the NI-MFGDP-MS measurement. These findings provide a guideline and a supplement to the chemical libraries for rapid and accurate detection of explosives. The method shows great potential for fast, in situ, on-line and high throughput detection of explosives in the field of antiterrorism. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Combined General/Epidural Anesthesia on Hemodynamics, Respiratory Function, and Stress Hormone Levels in Patients with Ovarian Neoplasm Undergoing Laparoscopy.

PubMed

Xu, Qiang; Zhang, Hao; Zhu, Yan-Mei; Shi, Nian-Jun

2016-11-08

BACKGROUND The aim of this study was to evaluate the influence of combined general/epidural anesthesia (GEA) on hemodynamics, respiratory function and stress hormone levels in patients with ovarian neoplasm undergoing laparoscopy. MATERIAL AND METHODS A total of 177 patients with ovarian neoplasm (screened by inclusion/exclusion criteria) receiving laparoscopy were divided into groups G (general anesthesia alone), L1.0 (GEA with 1.0% lidocaine), and L1.5 (GEA with 1.5% lidocaine). Hemodynamics, respiratory parameters and stress hormone levels in the 3 groups were recorded and analyzed. RESULTS Hemodynamic indexes and PaO2/PaCO2 in group L1.0 showed no differences at each time point (all P>0.05). At the end of anesthesia tracheal intubation (T1), 10 min after pneumoperitoneum (T2) and the end of anesthesia tracheal extubation (T3), there were significant differences in hemodynamic indexes, respiratory parameters, epinephrine (E), and noradrenalin (NE) of group G/L1.5, compared with before anesthesia induction (T0) (all P<0.05). Compared with group G, there were big differences in dosage of anesthetics (sufentanil, vecuronium, and propofol) and pharmaceutic adjuvants (ephedrine, atropine, and nitroglycerin), postoperative recovery time, extubation time, and incidence of agitation in group L1.0/L1.5 (all P<0.05). CONCLUSIONS GEA can improve the quality and efficiency in laparoscopy for ovarian neoplasm, with the advantages of reduced anesthetics dosage, satisfactory postoperative analgesia, maintained hemodynamic stability, excellent uterine relaxation, and reduced time of anesthesia induction, surgery, recovery, and extubation. In addition, compared with group L1.5, group L1.0 was more secure and worthy of clinical promotion in laparoscopy.

Enhanced alkaline hydrolysis and biodegradability studies of nitrocellulose-bearing missile propellant

NASA Technical Reports Server (NTRS)

Sidhoum, Mohammed; Christodoulatos, Christos; Su, Tsan-Liang; Redis, Mercurios

1995-01-01

Large amounts of energetic materials which have been accumulated over the years in various manufacturing and military installations must be disposed of in an environmentally sound manner. Historically, the method of choice for destruction of obsolete or aging energetic materials has been open burning or open detonation (OB/OD). This destruction approach has become undesirable due to air pollution problems. Therefore, there is a need for new technologies which will effectively and economically deal with the disposal of energetic materials. Along those lines, we have investigated a chemical/biological process for the safe destruction and disposal of a double base solid rocket propellant (AHH), which was used in several 8 inch projectile systems. The solid propellant is made of nitrocellulose and nitroglycerin as energetic components, two lead salts which act as ballistic modifiers, triacetin as a plasticizer and 2-Nitrodiphenylamine (2-NDPA) as a stabilizer. A process train is being developed to convert the organic components of the propellant to biodegradable products and remove the lead from the process stream. The solid propellant is first hydrolyzed through an enhanced alkaline hydrolysis process step. Following lead removal and neutralization, the digested liquor rich in nitrates and nitrites is found to be easily biodegradable. The digestion rate of the intact ground propellant as well as the release of nitrite and nitrate groups were substantially increased when ultrasound were supplied to the alkaline reaction medium compared to the conventional alkaline hydrolysis. The effects of reaction time, temperature, sodium hydroxide concentration and other relevant parameters on the digestion efficiency and biodegradability have been studied. The present work indicates that the AHH propellant can be disposed of safely with a combination of physiochemical and biological processes.

Forearm Vascular Reactivity and Arterial Stiffness in Asymptomatic Subjects from the Community

PubMed Central

Malik, A. Rauoof; Kondragunta, Venkateswarlu; Kullo, Iftikhar J.

2010-01-01

Vascular reactivity may affect the stiffness characteristics of the arterial wall. We investigated the association between forearm microcirculatory and conduit artery function and measures of arterial stiffness in 527 asymptomatic non-Hispanic white adults without known cardiovascular disease. High-resolution ultrasonography of the brachial artery (ba) was performed to assess forearm microcirculatory function (ba blood flow velocity, local shear stress, and forearm vascular resistance at rest and during reactive hyperemia) and conduit artery function (ba flow-mediated dilatation baFMD and ba nitroglycerin-mediated dilatation baNMD). Arterial stiffness was assessed by cuff-derived brachial pulse pressure and aortic pulse wave velocity (aPWV) measured by applanation tonometry. In regression analyses that adjusted for heart rate, mean arterial pressure, height, cardiovascular risk factors, and hypertension medication and statin use, higher baseline ba systolic velocity and systolic shear stress were associated with greater pulse pressure (P=0.0002 and P=0.006, respectively) and higher aPWV (each P<0.0001). During hyperemia, lower ba mean velocity and lower mean shear stress were associated with higher pulse pressure (P=0.045 and P=0.036, respectively) while both systolic and mean velocity (P<0.0001 and P=0.002, respectively) and systolic and mean shear stress (P<0.0001 and P=0.003, respectively) were inversely associated with aPWV. baFMD was not associated with pulse pressure but was inversely associated with aPWV (P=0.011). baNMD was inversely associated with pulse pressure (P=0.0002) and aPWV (P=0.008). Our findings demonstrate that impaired forearm microvascular function (in the form of elevated resting blood flow velocity and impaired flow reserve) and impaired brachial artery reactivity are associated with increased arterial stiffness. PMID:18426995

A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena

PubMed Central

Schuhmacher, S; Schulz, E; Oelze, M; König, A; Roegler, C; Lange, K; Sydow, L; Kawamoto, T; Wenzel, P; Münzel, T; Lehmann, J; Daiber, A

2009-01-01

Background and purpose: The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Experimental approach: Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Key results: Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. Conclusions and implications: The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes. PMID:19563531

Use of Mass Spectrometric Vapor Analysis To Improve Canine Explosive Detection Efficiency.

PubMed

Ong, Ta-Hsuan; Mendum, Ted; Geurtsen, Geoff; Kelley, Jude; Ostrinskaya, Alla; Kunz, Roderick

2017-06-20

Canines remain the gold standard for explosives detection in many situations, and there is an ongoing desire for them to perform at the highest level. This goal requires canine training to be approached similarly to scientific sensor design. Developing a canine training regimen is made challenging by a lack of understanding of the canine's odor environment, which is dynamic and typically contains multiple odorants. Existing methodology assumes that the handler's intention is an adequate surrogate for actual knowledge of the odors cuing the canine, but canines are easily exposed to unintentional explosive odors through training material cross-contamination. A sensitive, real-time (∼1 s) vapor analysis mass spectrometer was developed to provide tools, techniques, and knowledge to better understand, train, and utilize canines. The instrument has a detection library of nine explosives and explosive-related materials consisting of 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 2,4,6-trinitrotoluene (TNT), nitroglycerin (NG), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), pentaerythritol tetranitrate (PETN), triacetone triperoxide (TATP), hexamethylene triperoxide diamine (HMTD), and cyclohexanone, with detection limits in the parts-per-trillion to parts-per-quadrillion range by volume. The instrument can illustrate aspects of vapor plume dynamics, such as detecting plume filaments at a distance. The instrument was deployed to support canine training in the field, detecting cross-contamination among training materials, and developing an evaluation method based on the odor environment. Support for training material production and handling was provided by studying the dynamic headspace of a nonexplosive HMTD training aid that is in development. These results supported existing canine training and identified certain areas that may be improved.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

PubMed

Dai, Yuk-Ling; Luk, Ting-Hin; Yiu, Kai-Hang; Wang, Mei; Yip, Pandora M C; Lee, Stephen W L; Li, Sheung-Wai; Tam, Sidney; Fong, Bonnie; Lau, Chu-Pak; Siu, Chung-Wah; Tse, Hung-Fat

2011-06-01

Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Investigation of endothelial function by pulse contour analysis: a protocol for drug administration and timing of pulse contour assessment

PubMed Central

Gordon, Sarah E; Cartwright, Neil; Griffiths, Mark J D

2009-01-01

AIMS Pulse contour analysis (PCA) obtained by finger photoplethysmography produces a digital volume pulse (DVP) including an inflection point in its down-slope. The reflection index (RI: ratio of the inflection point height over the maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose and time interval for assessing endothelial function using PCA in healthy volunteers and patients with severe coronary artery disease. METHODS Time and dose to RI response relationships were constructed in 16 volunteers and nine patients to inhaled salbutamol (100–400 µg) or sublingual nitroglycerin (NTG; 25–400 µg). RESULTS For the volunteers, the time to maximum RI response to inhaled salbutamol and sublingual NTG was 10.73 ± 0.41 and 3.66 ± 0.21 min, respectively. A plateau in the RI response to salbutamol occurred between 5 and 15 min after inhalation and results were averaged over this period. A dose-dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05 and P < 0.001 by repeated-measures anova, respectively) in healthy volunteers. By contrast, in patients with severe coronary artery disease inhaled salbutamol (100–400 µg) did not cause a significant change in RI. CONCLUSIONS In healthy volunteers the RI response to inhaled salbutamol (100–200 µg) averaged over 5–15 min after administration may be used to investigate endothelial function by PCA. The response to sublingual NTG (50 µg) should be determined at 4 min. This technique may not be suitable for the assessment of endothelial function in subjects with extensive coronary artery disease owing to the small responses observed and potential confounding effect of vasoactive medication. PMID:19843066

Environmental impacts of training activities at an air weapons range.

PubMed

Bordeleau, Geneviève; Martel, Richard; Ampleman, Guy; Thiboutot, Sonia

2008-01-01

Within Canada, it has been recognized in the last decade that military training activities may have impacts on the environmental quality of training ranges. However, impacts of activities specific to Air Force Bases have not yet been intensely documented. A hydrogeological study was accomplished at the Cold Lake Air Weapons Range, Alberta, to evaluate the environmental impacts of using bombs, rockets, strafing, and open burning/open detonation (OB/OD) on the quality of soil, ground water, surface water, and lake sediments. Samples were analyzed for metals, anions, ammonium perchlorate (NH(4)ClO(4)), and energetic materials (EM). It was found that training activities did not result in measured values being exceeded on the basis of guidance values for surface water and lake sediments. Contamination by metals was mostly limited to soils, and some metals may be related to the use of bombs (Cd, Cu, Pb), strafe (Cu), and rockets (As, Ba, Cd, Cr, Cu, Fe, Ni, Pb, U, V, Zn). TNT (2,4,6-trinitrotoluene) was the main EM found in soils, while RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) was more common in ground water. Both are related to live bombing, while nitroglycerine (NG) is related to rocket use and was detected in soils only. Aluminum, nitrate, and ammonium perchlorate detected in ground water may be related to live bombing or rockets. OB/OD operations resulted in the presence of various EM in soils, and of perchlorate and nitrate in ground water. Contamination by metals and explosives in soils was localized around the targets and varied significantly in time; however, in ground water it was more constant and may persist for a period of several years after a target has been removed.

[Effect of Xinling Wan in treatment of stable angina pectoris: a randomized, double-blinded, placebo parallel-controlled, multicenter trial].

PubMed

Gao, Jian-Wei; Gao, Xue-Min; Zou, Ting; Zhao, Tian-Meng; Wang, Dong-Hua; Wu, Zong-Gui; Ren, Chang-Jie; Wang, Xing; Geng, Nai-Zhi; Zhao, Ming-Jun; Liang, Qiu-Ming; Feng, Xing; Yang, Bai-Song; Shi, Jun-Ling; Hua, Qi

2018-03-01

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group. Copyright© by the Chinese Pharmaceutical Association.

Endothelial dysfunction in normoglycaemic first-degree relatives of type 2 diabetes mellitus complicated with hyperuricaemia.

PubMed

Zhang, Junxia; Xiang, Lin; Zhang, Bilin; Cheng, Yangyang

2017-03-01

To reveal the effect of hyperuricaemia on endothelial function in normoglycaemic first-degree relatives of type 2 diabetes mellitus. In all, 40 first-degree relatives of type 2 diabetes mellitus with hyperuricaemia, 40 first-degree relatives of type 2 diabetes mellitus with normouricaemia and 35 healthy subjects without diabetic family history were recruited in this study. Anthropometric parameters as well as blood pressure, blood lipids, fasting blood glucose, fasting insulin, C-reactive protein, tumour necrosis factor-α and interleukin-6 were measured. Insulin resistance was assessed with homoeostasis model assessment index-insulin resistance index. To assess endothelial function, high-resolution ultrasonography was used for measuring flow- and nitroglycerine-mediated brachial artery vasodilation. When compared with control, flow-mediated dilation was lower in first-degree relatives with or without hyperuricaemia (both p < 0.001). When compared with first-degree relative subjects with normouricaemia, there were lower flow-mediated dilation ( p < 0.001) and higher levels of uric acid ( p < 0.001), fasting blood glucose ( p < 0.001), C-reactive protein ( p = 0.001), tumour necrosis factor-α ( p < 0.001) and interleukin-6 ( p < 0.001) in first-degree relative subjects with hyperuricaemia. Flow-mediated dilation was found to be negatively related to uric acid ( r = -0.597, p < 0.001). Stepwise multiple regressions demonstrated that uric acid was a significant determinant of flow-mediated dilation independent of other variables in first-degree relatives of type 2 diabetes mellitus (β = -0.677, p < 0.001; confidence interval: -0.010 to -0.006). Further endothelial dysfunction is found in normoglycaemic first-degree relatives of type 2 diabetes mellitus complicated with hyperuricaemia.

Effect of paricalcitol on endothelial function and inflammation in type 2 diabetes and chronic kidney disease.

PubMed

Thethi, Tina K; Bajwa, Muhammad A; Ghanim, Husam; Jo, Chanhee; Weir, Monica; Goldfine, Allison B; Umpierrez, Guillermo; Desouza, Cyrus; Dandona, Paresh; Fang-Hollingsworth, Ying; Raghavan, Vasudevan; Fonseca, Vivian A

2015-04-01

Patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD) have impaired endothelial function. Vitamin D and its analogs may play a role in regulation of endothelial function and inflammation. We studied effects of paricalcitol compared to placebo on endothelial function and markers of inflammation and oxidative stress in patients with T2DM and CKD. A double blind, randomized, placebo-controlled trial was conducted in 60 patients with T2DM and stage 3 or 4 CKD. Paricalcitol 1 mcg or placebo was administered orally once daily for three months. Brachial artery flow mediated dilatation (FMD), nitroglycerine mediated dilation (NMD), and plasma concentrations of inflammatory cytokines, tumor necrosis factor -α and interleukin-6, highly-sensitive C-reactive protein; endothelial surface proteins, intercellular adhesion molecule -1 and monocyte chemo attractant protein-1, and plasma glucose, insulin, free fatty acids, and urinary isoprostane were measured at baseline and end of three months. 27 patients in the paricalcitol group and 28 patients in the control group completed the study, though analysis of FMD at both time points was possible in 23 patients in each group. There was no significant difference in the change in FMD, NMD or the biomarkers examined after paricalcitol or placebo treatment. Treatment with paricalcitol at this dose and duration did not affect brachial artery FMD or biomarkers of inflammation and oxidative stress. The lack of significance may be due to the fact that the study patients had advanced CKD and that effects of paricalcitol are not additive to the effects of glycemic, lipid and anti-hypertensive therapies. Published by Elsevier Inc.

A physarum-inspired prize-collecting steiner tree approach to identify subnetworks for drug repositioning.

PubMed

Sun, Yahui; Hameed, Pathima Nusrath; Verspoor, Karin; Halgamuge, Saman

2016-12-05

Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning. Drug Similarity Networks (DSN) are generated using the chemical, therapeutic, protein, and phenotype features of drugs. In DSNs, vertex prizes and edge costs represent the similarities and dissimilarities between drugs respectively, and terminals represent drugs in the cardiovascular class, as defined in the Anatomical Therapeutic Chemical classification system. A new Physarum-inspired Prize-Collecting Steiner Tree algorithm is proposed in this paper to identify subnetworks. We apply both the proposed algorithm and the widely-used GW algorithm to identify subnetworks in our 18 generated DSNs. In these DSNs, our proposed algorithm identifies subnetworks with an average Rand Index of 81.1%, while the GW algorithm can only identify subnetworks with an average Rand Index of 64.1%. We select 9 subnetworks with high Rand Index to find drug repositioning opportunities. 10 frequently occurring drugs in these subnetworks are identified as candidates to be repositioned for cardiovascular diseases. We find evidence to support previous discoveries that nitroglycerin, theophylline and acarbose may be able to be repositioned for cardiovascular diseases. Moreover, we identify seven previously unknown drug candidates that also may interact with the biological cardiovascular system. These discoveries show our proposed Prize-Collecting Steiner Tree approach as a promising strategy for drug repositioning.

Peroxide generation by p47phox-Src activation of Nox2 has a key role in protein kinase C-induced arterial smooth muscle contraction.

PubMed

Gupte, Sachin A; Kaminski, Pawel M; George, Shimran; Kouznestova, Lioubov; Olson, Susan C; Mathew, Rajamma; Hintze, Thomas H; Wolin, Michael S

2009-04-01

Protein kinase C (PKC) stimulation of NAD(P)H oxidases (Nox) is an important component of multiple vascular disease processes; however, the relationship between oxidase activation and the regulation of vascular smooth muscle contraction by PKC remains poorly understood. Therefore, we examined the signaling cascade of PKC-elicited Nox activation and the role of superoxide and hydrogen peroxide in mediating PKC-induced vascular contraction. Endothelium-denuded bovine coronary arteries showed a PKC-dependent basal production of lucigenin (5 muM)-detected Nox oxidase-derived superoxide, which was stimulated fourfold by PKC activation with 10 muM phorbol 12,13-dibutyrate (PDBu). PDBu appeared to increase superoxide generation by Nox2 through both p47(phox) and peroxide-dependent Src activation mechanisms based on the actions of inhibitors, properties of Src phosphorylation, and the loss of responses in aorta from mice deficient in Nox2 and p47(phox). The actions of inhibitors of contractile regulating mechanisms, scavengers of superoxide and peroxide, and responses in knockout mouse aortas suggest that a major component of the contraction elicited by PDBu appeared to be mediated through peroxide derived from Nox2 activation stimulating force generation through Rho kinase and calmodulin kinase-II mechanisms. Superoxide generated by PDBu also attenuated relaxation to nitroglycerin. Peroxide-derived from Nox2 activation by PKC appeared to be a major contributor to the thromboxane A(2) receptor agonist U46619 (100 nM)-elicited contraction of coronary arteries. Thus a p47(phox) and Src kinase activation of peroxide production by Nox2 appears to be an important contributor to vascular contractile mechanisms mediated through activation of PKC.

Evidence for hydroxyl radical scavenging action of nitric oxide donors in the protection against 1-methyl-4-phenylpyridinium-induced neurotoxicity in rats.

PubMed

Banerjee, Rebecca; Saravanan, Karuppagounder S; Thomas, Bobby; Sindhu, Kizhake M; Mohanakumar, Kochupurackal P

2008-06-01

In the present study we provide evidence for hydroxyl radical (*OH) scavenging action of nitric oxide (NO*), and subsequent dopaminergic neuroprotection in a hemiparkinsonian rat model. Reactive oxygen species are strongly implicated in the nigrostriatal dopaminergic neurotoxicity caused by the parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). Since the role of this free radical as a neurotoxicant or neuroprotectant is debatable, we investigated the effects of some of the NO* donors such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine hydrochloride (SIN-1), sodium nitroprusside (SNP) and nitroglycerin (NG) on in vitro *OH generation in a Fenton-like reaction involving ferrous citrate, as well as in MPP+-induced *OH production in the mitochondria. We also tested whether co-administration of NO* donor and MPP+ could protect against MPP+-induced dopaminergic neurotoxicity in rats. While NG, SNAP and SIN-1 attenuated MPP+-induced *OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused up to 18-fold increase in *OH production in the latter reaction. Striatal dopaminergic depletion following intranigral infusion of MPP+ in rats was significantly attenuated by NG, SNAP and SIN-1, but not by SNP. Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO*, when administered similarly failed to attenuate MPP+-induced neurotoxicity in vivo. Conversely, long-time air-exposed SNP solution when administered in rats intranigrally, caused a dose-dependent depletion of the striatal dopamine. These results confirm the involvement of *OH in the nigrostriatal degeneration caused by MPP+, indicate the *OH scavenging ability of NO*, and demonstrate protection by NO* donors against MPP+-induced dopaminergic neurotoxicity in rats.

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

PubMed Central

2015-01-01

Abstract Organic nitrates, such as nitroglycerin (GTN), isosorbide-5-mononitrate and isosorbide dinitrate, and pentaerithrityl tetranitrate (PETN), when given acutely, have potent vasodilator effects improving symptoms in patients with acute and chronic congestive heart failure, stable coronary artery disease, acute coronary syndromes, or arterial hypertension. The mechanisms underlying vasodilation include the release of •NO or a related compound in response to intracellular bioactivation (for GTN, the mitochondrial aldehyde dehydrogenase [ALDH-2]) and activation of the enzyme, soluble guanylyl cyclase. Increasing cyclic guanosine-3′,-5′-monophosphate (cGMP) levels lead to an activation of the cGMP-dependent kinase I, thereby causing the relaxation of the vascular smooth muscle by decreasing intracellular calcium concentrations. The hemodynamic and anti-ischemic effects of organic nitrates are rapidly lost upon long-term (low-dose) administration due to the rapid development of tolerance and endothelial dysfunction, which is in most cases linked to increased intracellular oxidative stress. Enzymatic sources of reactive oxygen species under nitrate therapy include mitochondria, NADPH oxidases, and an uncoupled •NO synthase. Acute high-dose challenges with organic nitrates cause a similar loss of potency (tachyphylaxis), but with distinct pathomechanism. The differences among organic nitrates are highlighted regarding their potency to induce oxidative stress and subsequent tolerance and endothelial dysfunction. We also address pleiotropic effects of organic nitrates, for example, their capacity to stimulate antioxidant pathways like those demonstrated for PETN, all of which may prevent adverse effects in response to long-term therapy. Based on these considerations, we will discuss and present some preclinical data on how the nitrate of the future should be designed. Antioxid. Redox Signal. 23, 899–942. PMID:26261901

Transgenic overexpression of uncoupling protein 2 attenuates salt-induced vascular dysfunction by inhibition of oxidative stress.

PubMed

Ma, Shuangtao; Wang, Qiang; Zhang, Yan; Yang, Dachun; Li, De; Tang, Bing; Yang, Yongjian

2014-03-01

Ablation of uncoupling protein 2 (UCP2) has been involved in the enhancement of salt sensitivity associated with increased superoxide level and decreased nitric oxide (NO) bioavailability. However, the role of overexpression of UCP2 in salt-induced vascular dysfunction remains elusive. UCP2 transgenic (TG) and wild-type (WT) mice were placed on either a normal-salt (NS, 0.5%) or a high-salt (HS, 8%) diet for 12 weeks. Blood pressure (BP) and hypotensive responses were measured, and the vascular tone, superoxide level, and NO bioavailability in aortas were measured in each group. The TG mice had increased expression and function of UCP2 in vascular smooth muscle cells. The acetylcholine (ACh)- and nitroglycerin (NTG)-induced hypotensive responses and aortic relaxations were significantly blunted in WT mice fed with an HS diet compared with an NS diet. These harmful effects were prevented in UCP2 TG mice. The impairments of ACh- and NTG-induced relaxation in aorta were inhibited by the endothelial NO synthase (eNOS) inhibitor L-NAME and mitochondrial antioxidant MitoQ, respectively. The HS intake led to a significant increase in superoxide production and a comparable decrease in NO bioavailability in aortas, and these effects were blunted in UCP2 TG mice. The expression of UCP2 was slightly increased in the HS group. However, the expression and phosphorylation of eNOS were not affected by an HS diet and overexpression of UCP2. These findings suggest that overexpression of UCP2 can ameliorate salt-induced vascular dysfunction. This beneficial effect of UCP2 is mediated by decreased superoxide and reserved NO bioavailability.

Parallel decrease in arterial distensibility and in endothelium-dependent dilatation in young women with a history of pre-eclampsia.

PubMed

Pàez, Olga; Alfie, José; Gorosito, Marta; Puleio, Pablo; de Maria, Marcelo; Prieto, Noemì; Majul, Claudio

2009-10-01

Pre-eclampsia not only complicates 5 to 8% of pregnancies but also increases the risk of maternal cardiovascular disease and mortality later in life. We analyzed three different aspects of arterial function (pulse wave velocity, augmentation index, and flow-mediated dilatation), in 55 nonpregnant, normotensive women (18-33 years old) according to their gestational history: 15 nulliparous, 20 with a previous normotensive, and 20 formerly pre-eclamptic pregnancy. Former pre-eclamptic women showed a significantly higher augmentation index and pulse wave velocity (P < 0.001 and P < 0.05, respectively) and lower flow-mediated dilatation (p = 0.01) compared to control groups. In contrast, sublingual nitroglycerine elicited a comparable vasodilatory response in the three groups. The augmentation index correlated significantly with pulse wave velocity and flow-mediated dilatation (R = 0.28 and R = -0.32, respectively, P < 0.05 for both). No significant correlations were observed between augmentation index or flow-mediated dilatation with age, body mass index (BMI), brachial blood pressure, heart rate, or metabolic parameters (plasma cholesterol, glucose, insulin, or insulin resistance). Birth weight maintained a significantly inverse correlation with the augmentation index (R = -0.51, p < 0.002) but not with flow-mediated dilatation. Our findings revealed a parallel decrease in arterial distensibility and endothelium-dependent dilatation in women with a history of pre-eclampsia compared to nulliparous women and women with a previous normal pregnancy. A high augmentation index was the most consistent alteration associated with a history of pre-eclampsia. The study supports the current view that the generalized arterial dysfunction associated with pre-eclampsia persists subclinically after delivery.

Enjoying hobbies is related to desirable cardiovascular effects.

PubMed

Saihara, Keishi; Hamasaki, Shuichi; Ishida, Sanemasa; Kataoka, Tetsuro; Yoshikawa, Akiko; Orihara, Koji; Ogawa, Masakazu; Oketani, Naoya; Fukudome, Tsuyoshi; Atsuchi, Nobuhiko; Shinsato, Takuro; Okui, Hideki; Kubozono, Takuro; Ichiki, Hitoshi; Kuwahata, So; Mizoguchi, Etsuko; Fujita, Shoji; Takumi, Takuro; Ninomiya, Yuichi; Tomita, Kaai; Tei, Chuwa

2010-03-01

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 +/- 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% +/- 77% vs 25% +/- 37%, P < 0.05, 4% +/- 13% vs -3% +/- 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.

Effect of teriparatide treatment on endothelial function, glucose metabolism and inflammation markers in patients with postmenopausal osteoporosis.

PubMed

Celer, Ozgen; Akalın, Aysen; Oztunali, Cigdem

2016-10-01

Teriparatide, an anabolic agent used in the treatment of postmenopausal osteoporosis, can induce effects similar to primary hyperparathyroidism. Our objective was to evaluate the effects of teriparatide on endothelial functions, glucose metabolism and inflammation markers in patients diagnosed with postmenopausal osteoporosis. This was a single-centre, single-arm, 6-month prospective study. Twenty-three postmenopausal women over 65 years old with a lumbar spine or femoral neck T-score of -4·0 or lower and having at least two compression fractures in thoracic or lumbar spine were studied. Low-dose intermittent teriparatide (20 μg/day) was supplemented with calcium carbonate (1000 mg elemental calcium) and 880 IU cholecalciferol for 6 months. The biochemical parameters for glucose metabolism, inflammation and atherosclerosis were determined. For the assessment of vascular endothelial function, carotid intima-media thickness (CIMT), brachial artery intima-media thickness (BIMT), per cent change in flow-mediated dilation (FMD%) and nitroglycerine-induced dilations (NID%) were measured on ultrasonography. The fasting plasma glucose, homoeostatic model assessment of insulin resistance, fibrinogen, homocysteine and high-density lipoprotein cholesterol increased significantly with teriparatide treatment (P < 0·05 for all). Baseline CIMT and BIMT did not change significantly with 6 months of teriparatide treatment (P > 0·05); however, FMD% and NID% showed significant decrease after treatment (P < 0·01 for both). Intermittent teriparatide treatment may adversely affect some parameters of glucose metabolism, inflammation and endothelial function. On the basis of our findings, further large-scale and controlled studies are needed to clarify the exact effect of teriparatide treatment on glucose metabolism, inflammation and endothelial function. © 2016 John Wiley & Sons Ltd.

A randomised controlled trial evaluating the effect of potassium supplementation on vascular function and the renin-angiotensin-aldosterone system.

PubMed

Graham, U M; McCance, D R; Young, I S; Mullan, K R

2014-05-01

There is limited evidence on the effect of potassium supplementation on the vasculature in patients at increased cardiovascular risk. Potassium increases aldosterone and there is a strong association of hyperaldosteronism with poor cardiac outcomes. We aimed to determine whether potassium supplementation has a significant medium-term effect on aldosterone levels and, if so, what the overall effect of this is on vascular function in patients at moderate cardiovascular disease risk. Forty patients at moderate cardiovascular disease risk were included in a randomised placebo-controlled crossover study. Patients were assigned to 64 mmol potassium chloride or placebo for 6 weeks. Vascular function was assessed using pulse-wave analysis including the detection of a change in augmentation index to salbutamol and nitroglycerine-induced vasodilation. There was no change in augmentation index with potassium vs placebo (25.2±1.4 vs. 26.0±1.3%, respectively). Potassium improved brachial systolic blood pressure (131.8±2.2 vs. 137.1±2.4 mm Hg; P=0.013), central systolic blood pressure (123.2±2.3 vs. 128.4±2.3 mm Hg; P=0.011) and central diastolic blood pressure (80.3±1.3 vs. 83.7±1.4 mm Hg; P=0.019). Plasma renin activity and serum aldosterone both increased with potassium (P=0.001 and P=0.048 respectively). We found that potassium supplementation had no effect on endothelial function or pulse-wave analysis. It lowered brachial systolic and central blood pressure. It was associated with increased plasma renin activity and serum aldosterone.

Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women.

PubMed

Hallund, J; Bügel, S; Tholstrup, T; Ferrari, M; Talbot, D; Hall, W L; Reimann, M; Williams, C M; Wiinberg, N

2006-06-01

Soya isoflavones are thought to be cardioprotective due to their structural similarity to oestrogen. In order to investigate the effect of soya isoflavones on markers of endothelial function we conducted a randomised, double-blind, placebo-controlled, cross-over study with thirty healthy postmenopausal women. The women consumed cereal bars, with or without soya isoflavones (50 mg/d), for 8 weeks, separated by an 8-week washout period. Systemic arterial compliance (SAC), isobaric arterial compliance (IAC), flow-mediated endothelium-dependent vasodilation (FMD) and nitroglycerine-mediated endothelium-independent vasodilation (NMD) were measured at the beginning of the study and after each intervention period. Blood pressure (BP) and plasma concentrations of nitrite and nitrate (NOx) and endothelin-1 (ET-1) were measured at the beginning and end of each intervention period. NMD was 13.4 (SEM 2.0)% at baseline and 15.5 (SEM 1.1) % after isoflavone treatment compared with 12.4 (SEM 1.0)% after placebo treatment (P=0.03). NOx increased from 27.7 (SEM 2.7) to 31.1 (SEM 3.2) microM after isoflavones treatment compared with 25.4 (SEM 1.5) to 20.4 (SEM 1.1) microM after placebo treatment (P=0.003) and a significant increase in the NOx:ET-1 ratio (P=0.005) was observed after the isoflavone treatment compared with placebo. A significant difference in SAC after the isoflavone and placebo treatment was observed (P=0.04). No significant difference was found in FMD, IAC, BP and ET-1. In conclusion, 8 weeks' consumption of cereals bars enriched with 50 mg soya isoflavones/d increased plasma NOx concentrations and improved endothelium-independent vasodilation in healthy postmenopausal women.

Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke.

PubMed

Chan, Yap-Hang; Lau, Kui-Kai; Yiu, Kai-Hang; Li, Sheung-Wai; Chan, Hiu-Ting; Fong, Daniel Yee-Tak; Tam, Sidney; Lau, Chu-Pak; Tse, Hung-Fat

2008-11-01

To investigate the effect of oral isoflavone supplement on vascular endothelial function in patients with established cardiovascular disease. A randomized, double-blinded, placebo-controlled trial was performed to determine the effects of isoflavone supplement (80 mg/day, n = 50) vs. placebo (n = 52) for 12 weeks on brachial flow-mediated dilatation (FMD) in patients with prior ischaemic stroke. Compared with controls, FMD at 12 weeks was significantly greater in isoflavone-treated patients [treatment effect 1.0%, 95% confidence interval (95% CI) 0.1-2.0, P = 0.035]. Adjusted for baseline differences in FMD, isoflavone treatment was independently associated with significantly less impairment of FMD at 12 weeks (odds ratio 0.32, 95% CI 0.13-0.80, P = 0.014). The absolute treatment effect of isoflavone on brachial FMD was inversely related to baseline FMD (r = -0.51, P < 0.001), suggesting that vasoprotective effect of isoflavone was more pronounced in patients with more severe endothelial dysfunction. Moreover, isoflavone treatment for 12 weeks resulted in a significant decrease in serum high-sensitivity (hs)-C-reactive protein level (treatment effect -1.7 mg/L, 95% CI -3.3 to -0.1, P = 0.033). Nevertheless, isoflavone did not have any significant treatment effects on nitroglycerin-mediated dilatation, blood pressure, heart rate, serum levels of fasting glucose and insulin, haemoglobin A1c, and oxidative stress as determined by serum superoxide dismutase, 8-isoprostane, and malondialdehyde (all P > 0.05). This study demonstrated that 12 week isoflavone treatment reduced serum hs-C-reactive protein and improved brachial FMD in patients with clinically manifest atherosclerosis, thus reversing their endothelial dysfunction status. These findings may have important implication for the use of isoflavone for secondary prevention in patients with cardiovascular disease, on top of conventional interventions.

Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease.

PubMed

Widlansky, Michael E; Hamburg, Naomi M; Anter, Elad; Holbrook, Monika; Kahn, David F; Elliott, James G; Keaney, John F; Vita, Joseph A

2007-04-01

Epidemiological studies demonstrate an inverse relation between dietary flavonoid intake and cardiovascular risk. Recent studies with flavonoid-containing beverages suggest that the benefits of these nutrients may relate, in part, to improved endothelial function. We hypothesized that dietary supplementation with epigallocatechin gallate (EGCG), a major catechin in tea, would improve endothelial function in humans. We examined the effects of EGCG on endothelial function in a double blind, placebo-controlled, crossover design study. We measured brachial artery flow-mediated dilation by vascular ultrasound at six time points: prior to treatment with EGCG or placebo, two hours after an initial dose of EGCG (300 mg) or placebo, and after two weeks of treatment with EGCG (150 mg twice daily) or placebo. The order of treatments (EGCG or placebo) was randomized and there was a one-week washout period between treatments. A total of 42 subjects completed the study, and brachial artery flow-mediated dilation improved from 7.1 +/- 4.1 to 8.6 +/- 4.7% two hours after the first dose of 300 mg of EGCG (P = 0.01), but was similar to baseline (7.8 +/- 4.2%, P = 0.12) after two weeks of treatment with the final measurements made approximately 14 hours after the last dose. Placebo treatment had no significant effect, and there were no changes in reactive hyperemia or the response to sublingual nitroglycerin. The changes in vascular function paralleled plasma EGCG concentrations, which increased from 2.6 +/- 10.9 to 92.8 +/- 78.7 ng/ml after acute EGCG (P < 0.001), but were unchanged from baseline after two weeks of treatment (3.4 +/- 13.1 ng/ml). EGCG acutely improves endothelial function in humans with coronary artery disease, and may account for a portion of the beneficial effects of flavonoid-rich food on endothelial function.

Systemic oxidoreductive balance and vascular function in individuals without clinical manifestation of atherosclerosis

PubMed Central

Majer, Marcin; Gackowski, Daniel; Różalski, Rafał; Siomek-Górecka, Agnieszka; Oliński, Ryszard; Budzyński, Jacek

2017-01-01

Introduction Endothelial dysfunction is recognized as the earliest disorder in the development of atherosclerosis, in the pathogenesis of which oxidative stress plays a crucial role. The aim of this study was to determine the relationships between non-invasive parameters of vascular dysfunction and oxidative stress. Material and methods Forty-eight individuals without clinical manifestation of atherosclerosis were studied. The plasma concentrations of the following were determined in all 48 subjects: retinol, ascorbic acid, α-tocopherol and uric acid, as well as the products of oxidative DNA damage repair: 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) in blood leukocytes and urine, and 8-oxo-7,8-dihydroguanine (8-oxoGua) in urine. The following parameters of vascular dysfunction were also examined: flow- (FMD) and nitroglycerin- (NMD) mediated dilatation of the brachial artery, pulse pressure (PP), distensibility coefficient (DC), pulsation (PI) and resistance (RI) index, carotid intima-media thickness (cIMT), and ankle-brachial index (ABI). Results Individuals with an FMD value of ≥ 8.8% had significantly higher blood concentrations of antioxidative vitamins and lower concentrations of 8-oxodG in their urine and blood leukocytes than their counterparts. Blood concentration of alpha-tocopherol or ascorbic acid positively correlated with FMD, PI, RI, DC and ABI and negatively with PP and cIMT. The reverse was the case for 8-oxodG in urine and leukocytes. In multiple regression analysis, markers of oxidative DNA damage positively determined the variance in PP and ABI. Conclusions In persons without clinical manifestation of atherosclerosis, oxidative stress was an independent factor associated with vascular wall dysfunction, and a better predictor than smoking and blood concentrations of glucose, lipids and creatinine. PMID:29242843

Flow-mediated vasodilation is augmented in a corkscrew collateral artery compared with that in a native artery in patients with thromboangiitis obliterans (Buerger disease).

PubMed

Fujii, Yuichi; Fujimura, Noritaka; Mikami, Shinsuke; Maruhashi, Tatsuya; Kihara, Yasuki; Chayama, Kazuaki; Noma, Kensuke; Higashi, Yukihito

2011-12-01

A healthy endothelium maintains vascular tone and structure. The purpose of this study was to evaluate endothelial function in corkscrew collateral arteries in Buerger disease. We measured flow-mediated vasodilation (FMD) in corkscrew arteries in 26 patients with Buerger disease, in control arteries in 26 healthy subjects, and in native arteries in 16 patients with Buerger disease. Hyperemic flow was lower in corkscrew arteries than in native arteries in patients with Buerger disease and in control arteries in healthy subjects. There was no significant difference between hyperemic flow in patients with Buerger disease in whom measurements were performed in native arteries and that in healthy subjects. FMD was lower in corkscrew arteries and native arteries in patients with Buerger disease than in control arteries in healthy subjects. There was no significant difference between FMD in corkscrew arteries in patients with Buerger disease and in that in native arteries. The ratio of FMD to hyperemic flow was significantly smaller in native arteries in patients with Buerger disease than in corkscrew arteries and in control arteries in healthy subjects (5.5 ± 6.2 vs 8.8 ± 8.9 and 9.6 ± 7.6 mL/min, P < .001, respectively). There was no significant difference in the ratio of FMD to hyperemic flow between corkscrew arteries in Buerger disease and control arteries in healthy subjects. Nitroglycerin-induced vasodilation was similar in all leg arteries. Endothelial function of a corkscrew collateral artery in patients with Buerger disease is maintained, while endothelial function is impaired in a native artery in Buerger disease. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Treatment of Angina and Microvascular Coronary Dysfunction

PubMed Central

Samim, Arang; Nugent, Lynn; Mehta, Puja K.; Shufelt, Chrisandra; Merz, C. Noel Bairey

2014-01-01

Opinion statement Microvascular coronary dysfunction (MCD) is an increasingly recognized cause of cardiac ischemia and angina, more commonly diagnosed in women. Patients with MCD present with the triad of persistent chest pain, ischemic changes on stress testing, and no obstructive coronary artery disease (CAD) on cardiac catheterization. Data from National Heart, Lung and Blood Institute (NHLBI)-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study has shown that the diagnosis of MCD is not benign, with a 2.5% annual risk of adverse cardiac events including myocardial infarction, stroke, congestive heart failure, or death. The gold standard diagnostic test for MCD is an invasive coronary reactivity test (CRT), which uses acetylcholine, adenosine, and nitroglycerin to test the endothelial dependent and independent, microvascular and macrovascular coronary function. The CRT allows for diagnostic and treatment options as well as further risk stratifying patients for future cardiovascular events. Treatment of angina and MCD should be aimed at ischemia disease management to reduce risk of adverse cardiac events, ameliorating symptoms to improve quality of life, and to decrease the morbidity from unnecessary and repeated cardiac catheterization in patients with open coronary arteries. A comprehensive treatment approach aimed at risk factor managment, including lifestyle counseling regarding smoking cessation, nutrition and physical activity should be initiated. Current pharmacotherapy for MCD can include the treatment of microvascular endothelial dysfunction (statins, angiotensin-converting enzyme inhibitor, low dose aspirin), as well as treatment for angina and myocardial ischemia (beta blockers, calcium channel blockers, nitrates, ranolazine). Additional symptom management techniques can include tri-cyclic medication, enhanced external counterpulsation, autogenic training, and spinal cord stimulation. While our current therapies are effective in the treatment of angina and MCD, large randomized outcome trials are needed to optimize strategies to improve morbidity and mortality. PMID:20842559

Chemical Composition and Antimigraine Activity of Essential Oil of Angelicae dahuricae Radix.

PubMed

Sun, Jingbo; Li, He; Sun, Jinghui; Liu, Huimin; Chen, Jianguang; Wang, Chunmei

2017-08-01

The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO 2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio. The optimal conditions for CO 2 supercritical fluid extraction of EOAD, as determined by orthogonal test [L 9 (3 4 )], were as follows: 2 h extraction time, 20 MPa pressure, 40°C temperature, and 30 mesh. The yield of EOAD was 1.8%. On gas chromatography-mass spectrometry, 45 peaks were found in EOAD, and 22 compounds were identified and quantified. The main constituents of EOAD were 1-dodecanol (13.71%), elemene (7.54%), palmitic acid ethyl ester (7.32%), α-pinene (6.25%), and 1-pentadecanol (6.08%). Compared with rat migraine model controls, EOAD (35, 70, and 140 mg/kg) significantly reduced the number of head shaking, head scratching, and hind leg shooting events, decreased serum and brain NO levels, decreased plasma CGRP, and increased ET levels in rats. ET/NO ratio was elevated to 28.68 in the EOAD high-dose group. EOAD ameliorates NTG-induced migraine in rats likely by modulating the levels of vasoactive substances.

Protective effects of vitamin E against myocardial ischemia/reperfusion injury in rats.

PubMed

Saleh, Nermine K; Saleh, Hanan A

2010-02-01

To clarify the cardioprotective effects of a short course of vitamin E treatment (vit E) as compared with a nitric oxide donor, nitroglycerin (GTN) against ischemia-reperfusion induced heart injury in rats. This randomized control study was conducted in the Physiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt from 1st June to 31 August 2009. This work was undertaken on 28 female Wistar rats weighing 150- 200 gm. Rats were allocated into 4 groups; control group (non-treated), GTN-treated group (rats received GTN intraperitoneally 25 minutes before sacrifice, in a dose of 120 ug/kg body weight), vit E-treated group (rat received vit E by oral tubal feeding 16-20 hours before sacrifice, in a dose of 250 mg/rat), and vit E and GTN-treated group (rats received vit E and GTN as in both GTN-treated group and vit E -treated group). After sacrifice, the hearts were excised and perfused in a Langendorff preparation and subjected to 30 minutes global ischemia and reperfused for 30 minutes. Following reperfusion, heart tissues were used for assessment of malondialdehyde (MDA) and nicotinamide adenine dinucleotide (NAD)+, and for histological examination. Vitamin E treatment resulted in an enhanced post-ischemic recovery of systolic function in vit E-treated groups (vit E-treated group, and vit E and GTN-treated group) compared to the control group. Post-ischemic recovery of coronary flow was enhanced in the vit E-treated group compared to the GTN-treated group. Post ischemic tissue degeneration indicators: MDA, and NAD+ indicated a cardioprotective effect of vit E. Histological study revealed marked improvement of myocytes and mitochondrial structure in the vit E-treated group as compared with the control group. Preconditioning with vit E treatment afforded substantial recovery of post-ischemic contractile, and vascular functions compared to GTN treatment, the mechanism might involve less opening of mitochondrial permeability transition during postischemic reperfusion.

Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.

PubMed

Shechter, M; Ginsberg, S; Scheinowitz, M; Feinberg, M S; Laron, Z

2007-04-01

Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress. Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls. All subjects underwent symptom-limited exercise testing (Bruce protocol). LS patients had a significantly higher body mass index (29+/-6 vs. 25+/-2 kg/m(2), p=0.04), lower low-density lipoprotein cholesterol (142+/-28 vs. 176+/-12 mg/dl, p=0.03) and a smaller mean brachial artery diameter (4.63+/-0.72 vs. 5.70+/-1.06 mm, p=0.01) compared to controls. However, brachial artery %FMD and %NTG were not significantly different between the LS patients and controls (13.1+/-6.2% vs. 15.4+/-5.2%, p=0.28 and 22.3+/-6.0% vs. 18.9+/-6.2%, p=0.30; respectively). Cardiac performance, assessed by exercise duration time and metabolic equivalents (METs), was significantly greater in control subjects than in LS patients (10.3+/-2.0 vs. 6.0+/-1.4 min, p<0.01 and 10.2+/-2.0 vs. 7.2+/-1.4 METs, p<0.01; respectively). FMD was found to be within normal limits in non-IGF-I-treated adult patients with LS, despite congenital absence of IGF-I and obesity.

Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association.

PubMed

Takahashi, Jun; Nihei, Taro; Takagi, Yusuke; Miyata, Satoshi; Odaka, Yuji; Tsunoda, Ryusuke; Seki, Atsushi; Sumiyoshi, Tetsuya; Matsui, Motoyuki; Goto, Toshikazu; Tanabe, Yasuhiko; Sueda, Shozo; Momomura, Shin-ichi; Yasuda, Satoshi; Ogawa, Hisao; Shimokawa, Hiroaki

2015-01-21

Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA. A total of 1429 VSA patients (median 66 years; male/female, 1090/339) were enrolled. The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the study patients, 695 (49%) were treated with nitrates, including conventional nitrates [e.g. nitroglycerin (GTN), isosorbide mono- and dinitrate] in 551 and nicorandil in 306. Calcium channel blockers were used in >90% of patients. During the median follow-up period of 32 months, 85 patients (5.9%) reached the primary endpoint. Propensity score-matched analysis demonstrated that the cumulative incidence of MACE was comparable between the patients with and those without nitrates [11 vs. 8% at 5 years; hazard ratio (HR): 1.28; 95% confidence interval (CI): 0.72-2.28, P = 0.40]. Although nicorandil itself had a neutral prognostic effect on VSA (HR: 0.80; 95% CI: 0.28-2.27, P = 0.67), multivariable Cox model revealed the potential harm of concomitant use of conventional nitrates and nicorandil (HR: 2.14; 95% CI: 1.02-4.47; P = 0.044), particularly when GTN and nicorandil were simultaneously administered. Chronic nitrate therapy did not improve the long-term prognosis of VSA patients when combined with CCBs. Furthermore, the VSA patients with multiple nitrates would have increased risk for cardiac events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.