Nitroglycerin Group Research Articles

Feasibility of Nitroglycerin Patch as a Pretreatment for the Distal Radial Approach: Study Protocol for a Randomized Controlled Trial (DRANG Study)

BackgroundThe distal radial approach (DRA) is a novel catheter cannulation technique to access the distal radial artery for coronary angiography (CAG). It is associated with less occurrence of puncture site occlusion than the conventional transradial approach. However, cannulation failure occasionally occurs due to difficulty in puncturing the smaller distal radial artery. Nitroglycerin is expected to improve the rate of successful DRA via its vasodilative and vasospasm-preventive effects. MethodsThe DRA in CAG using transdermal NitroGlycerin patch (DRANG) study is a single-center, double-arm, parallel-assignment, double-blinded, randomized, controlled trial. Eligible patients with angina pectoris who are scheduled to receive CAG via DRA at the National Cerebral and Cardiovascular Center will be enrolled and allocated to the nitroglycerin group (n = 46) or the no-treatment group (n = 46). The nitroglycerin group will receive a transdermal nitroglycerin patch pre-integrated with a covering material that completely conceals the patch on their upper arm on the puncture side. The no-treatment group will receive only the covering material. Applications are performed 2–8 h before puncture while the patient wears an eye mask. Physicians who are blinded to the allocation and have similar experience with DRA puncture will perform DRA using the Seldinger technique with a 22-gauge needle. The primary outcome is the rate of successful palpation-guided distal radial artery cannulation with the first puncture. The secondary outcomes are the rate of successful distal radial artery cannulation, number of punctures, procedure time, use of ultrasound guidance, diameter of the distal radial artery and changes before and after patch application, and occurrence of arterial vasospasm, occlusion, or hypotension. ConclusionsThis study will allow us to determine the impact of a transdermal nitroglycerin patch on the rate of successful DRA and validate its effectiveness as a DRA pretreatment. Trial registrationjRCTs051210128.

Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial

Hypoxia has been associated with chemoradioresistance secondary to vascular endothelial growth factor receptor induced by hypoxia-induced factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in tissues, and this may have antiangiogenic, proapoptotic, and antiefflux effects. Particularly, epidermal growth factor-mutated (EGFRm) tumor cell lines have been shown to overexpress both vascular endothelial growth factor and HIF. In this phase 2 study, we evaluated the effect of transdermal NTG plus whole brain radiation therapy (WBRT) in patients with non-small cell lung cancer (NSCLC) with brain metastases (BM). This was an open-label, phase 2 clinical trial with 96 patients with NSCLC and BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. The primary endpoint was intracranial objective response rate (iORR) evaluated 3 months posttreatment. NTG was administered using a transdermal 36-mg patch from Monday through Friday throughout WBRT administration (10 days). The protocol was retrospectively registered at ClinicalTrials.gov (NCT04338867). Fifty patients were allocated to the control group, and 46 were allocated to the experimental group (NTG); among these, 26 (52%) had EGFRm in the control group and 21 (45.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response compared with controls (56.5% [n = 26/46 evaluable patients] vs 32.7% [n = 16/49 evaluable patients]; relative risk, 1.73; 95% confidence interval [CI], 1.08-2.78; P = .024). Additionally, patients who received NTG + WBRT had an independently prolonged intracranial progression-free survival (ICPFS) compared with those who received WBRT alone (27.7 vs 9.6; hazard ratio [HR], 0.5; 95% CI, 0.2-0.9; P = .020); this positively affected overall progression-free survival among patients who received systemic therapy (n = 88; HR, 0.5; 95% CI, 0.2-0.9; P = .043). The benefit of ICPFS (HR, 0.4; 95% CI, 0.2-0.9; P = .030) was significant in the EGFRm patient subgroup. No differences were observed in overall survival. A significantly higher rate of vomiting presented in the NTG arm of the study (P = .016). The concurrent administration of NTG and radiation therapy improves iORR and ICPFS among patients with NSCLC with BM. The benefit in ICPFS is significant in the EGFRm patient subgroup.

Cerebral Oximetry-Monitored Nitroglycerin Infusion and Tissue Perfusion during Rewarming of Cardiopulmonary Bypass in Cardiac Surgery: A Prospective Randomized Trial.

Background: Nitroglycerin facilitates microcirculation and oxygen delivery through vasodilation. The purpose of this study was to clarify the effects of nitroglycerin-induced vasodilation and potential hypotension on tissue perfusion under cerebral oximetry monitoring during rewarming in cardiopulmonary bypass. Methods: Elective cardiac surgical patients were randomly assigned to either a nitroglycerin group (n = 32) with an intravenous infusion of 1–5 mcg/kg/min or a control group (n = 31) with 0–0.1 mcg/kg/min infusion, since the initiation of rewarming. Perioperative arterial blood gas data were collected in addition to hemodynamic variables, cerebral oximetry values, urine output, and postoperative outcomes. Results: Nearly one-fifth (6/32) of patients in the nitroglycerin group experienced transient (≤5 min) profound hypotension (mean arterial blood pressure ≤40 mmHg) after the initiation of infusion. There were no significant differences between groups in terms of perioperative levels of cerebral oximetry, cardiac index, plasma glucose, lactate, bicarbonate, base excess, or post-bypass activated coagulation time. In the nitroglycerin group, urine output was nonsignificantly higher during cardiopulmonary bypass (p = 0.099) and within 8 h after surgery (p = 0.157). Perioperative transfused blood products, postoperative inotropic doses, extubation time, and intensive care unit stay were comparable for the two groups. Conclusions: Initiation of intravenous nitroglycerin infusion (at 1–5 mcg/kg/min) during rewarming in hypothermic cardiopulmonary bypass resulted in transient profound hypotension in one-fifth of patients and did not improve perioperative cerebral oxygenation, tissue perfusion, and coagulation in cardiac surgery.

Classical prescription Dachuanxiong Formula delays nitroglycerin-induced pain response in migraine mice through reducing endothelin-1 level and regulating fatty acid biosynthesis

Ethnopharmacological relevanceDachuanxiong Formula (DCXF) is a classical Chinese medicine prescription and is composed of dried rhizomes from Ligusticum striatum DC. (Chuanxiong Rhizoma) and Gastrodia elata Bl. (Gastrodiae Rhizoma) at the ratio of 4:1 (w/w). It has been used as Chinese medicine prescription for thousands of years. DCXF is used traditionally to treat many diseases, including migraine, atherosclerosis and ischemic stroke. Aim of the studyThis study aimed to investigate the effects of DCXF on pain response in migraine mice, and the underlying mechanisms using proteomics and bioinformatics analyses. Materials and methodsDCXF extract was prepared by mixing Chuanxiong Rhizoma and Gastrodiae Rhizoma at a mass ratio of 4:1 (w/w). After extraction, the extract was filtered prior to high performance liquid chromatography (HPLC) analysis. Nitroglycerin (NTG) was used to establish a mouse migraine model, and a behaviour study was conducted by hot plate test. In addition, proteomics and bioinformatics studies were conducted to investigate the mechanisms of DCXF-mediating anti-migraine treatment. ResultsOur results showed that there were significant differences in the latencies between NTG-treated and DCXF low dose- and high doses-treated groups at 30 min after NTG injection, this suggested that DCXF could ameliorate pain response in migraine mice. Besides, the plasma levels of endothelin-1 were also measured. NTG group significantly enhanced the endothelin-1 level compared to the control group. In contrast, DCXF low dose and high dose groups significantly reduced this level compared to NTG group. In addition, the underlying mechanisms were also investigated. Our results demonstrated that the anti-migraine treatment of DCXF was highly associated with fatty acid synthesis, suggesting that DCXF ameliorated pain response through reducing endothelin-1 level and regulating fatty acid synthesis. ConclusionsThe present study revealed the anti-migraine effect of DCXF in migraine mice and provided insights into the mechanisms of DCXF-mediating anti-migraine treatment.

Pre-hospital transdermal glyceryl trinitrate in patients with stroke mimics: data from the RIGHT-2 randomised-controlled ambulance trial

BackgroundPrehospital stroke trials will inevitably recruit patients with non-stroke conditions, so called stroke mimics. We undertook a pre-specified analysis to determine outcomes in patients with mimics in the second Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial (RIGHT-2).MethodsRIGHT-2 was a prospective, multicentre, paramedic-delivered, ambulance-based, sham-controlled, participant-and outcome-blinded, randomised-controlled trial of transdermal glyceryl trinitrate (GTN) in adults with ultra-acute presumed stroke in the UK. Final diagnosis (intracerebral haemorrhage, ischaemic stroke, transient ischaemic attack, mimic) was determined by the hospital investigator. This pre-specified subgroup analysis assessed the safety and efficacy of transdermal GTN (5 mg daily for 4 days) versus sham patch among stroke mimic patients. The primary outcome was the 7-level modified Rankin Scale (mRS) at 90 days.ResultsAmong 1149 participants in RIGHT-2, 297 (26%) had a final diagnosis of mimic (GTN 134, sham 163). The mimic group were younger, mean age 67 (SD: 18) vs 75 (SD: 13) years, had a longer interval from symptom onset to randomisation, median 75 [95% CI: 47,126] vs 70 [95% CI:45,108] minutes, less atrial fibrillation and a lower systolic blood pressure and Face-Arm-Speech-Time tool score than the stroke group. The three most common mimic diagnoses were seizure (17%), migraine or primary headache disorder (17%) and functional disorders (14%). At 90 days, the GTN group had a better mRS score as compared to the sham group (adjusted common odds ratio 0.54; 95% confidence intervals 0.34, 0.85; p = 0.008), a difference that persisted at 365 days. There was no difference in the proportion of patients who died in hospital, were discharged to a residential care facility, or suffered a serious adverse event.ConclusionsOne-quarter of patients suspected by paramedics to have an ultra-acute stroke were subsequently diagnosed with a non-stroke condition. GTN was associated with unexplained improved functional outcome observed at 90 days and one year, a finding that may represent an undetected baseline imbalance, chance, or real efficacy. GTN was not associated with harm.Trial registrationThis trial is registered with International Standard Randomised Controlled Trials Number ISRCTN 26986053.

The effects of neonatal maternal deprivation and chronic unpredictable stresses on migraine-like behaviors in adult rats

BackgroundStress is known to cause migraine. This study investigates the effects of neonatal maternal deprivation (MD) and chronic unpredictable stress (CUS) on migraine in rats. MethodsSeventy rats were randomly divided into ten groups (five groups of each sex, and seven rats/group). The groups included: untreated intact, nitroglycerin (NTG) only, NTG + MD, NTG + CUS (10 weeks after birth), and NTG + MD + CUS. For the induction of MD, pups were separated from their mothers from postnatal day 2 to day 14. The CUS was conducted by daily exposure to different stressors for 2 weeks. For the induction of migraine after stress, NTG (5 mg/kg/IP) was administered every second day for 9 days. Afterward, NTG-related symptoms, including climbing behavior, facial rubbing, body grooming, freezing behavior, and head-scratching, were recorded for 90 min. Statistical differences between the groups were analyzed by one-way and two-way ANOVA followed by the Newman–Keuls test. ResultsMigraine symptoms, including increased head-scratching, facial rubbing, and decreased climbing behavior, were more significant in females than in males. Head scratching and facial rubbing increased in stressed females, but not in males as compared to NTG-treated rats. Body grooming was significantly decreased in MD males compared to the NTG group. The effects of NTG in MD + CUS on the rats did not differ from those in the MD or CUS groups. ConclusionsMD and CUS had a sex-related aggravating effect on the development of migraine, while the combination of MD and CUS had no additive migraine-aggravating effect.

Nicardipine versus nitroglycerin for hypertensive acute heart failure syndrome: a single-center observational study.

Objective: Nitroglycerin is a first-line treatment for hypertensive acute heart failure syndrome (AHFS). However, nicardipine is frequently used to treat hypertensive emergencies, including AHFS. In this study, we compared the effectiveness of nicardipine and nitroglycerin in patients with hypertensive AHFS.Patients and Methods: This single-center, retrospective, observational study was conducted at the intensive care unit of a Japanese hospital. Patients diagnosed with AHFS and systolic blood pressure 140 mmHg on arrival between April 2013 and March 2021 were included. The outcomes were the time to optimal blood pressure control, duration of continuous infusion of antihypertensive agents, duration of positive pressure ventilation, need for additional antihypertensive agents, length of hospital stay, and body weight changes. Outcomes were compared between the nicardipine and nitroglycerin groups. We also compared these outcomes between the groups after excluding patients who received renal replacement therapy.Results: Fifty-eight patients were enrolled (26 and 32 patients were treated with nitroglycerin and nicardipine, respectively). The nicardipine group had a shorter time to optimal blood pressure control (2.0 [interquartile range, 2.0–8.5] h vs. 1.0 [0.5–2.0] h), shorter duration of continuous anti-hypertensive agent infusion (3.0 [2.0–5.0] days vs. 2.0 [1.0–2.0] days), less frequent need for additional anti-hypertensive agents (1 patients [3.1%] vs. 11 patients [42.3%]), and shorter length of hospital stay (17.5 [10.0–33.0] days vs. 9.0 [5.0–15.0] days) than the nitroglycerin group. The duration of positive pressure ventilation and body weight changes were similar between the groups. The outcomes were similar after excluding patients who received renal replacement therapy.Conclusion: Nicardipine may be more effective than nitroglycerin for treating hypertensive AHFS.

The role of basolateral amygdala orexin 1 receptors on the modulation of pain and psychosocial deficits in nitroglycerin-induced migraine model in adult male rats.

BackgroundMigraine headaches have been associated with sensory hyperactivity and anomalies in social/emotional responses. The main objective of this study was to evaluate the potential involvement of orexin 1 receptors (Orx1R) within the basolateral amygdala (BLA) in the modulation of pain and psychosocial dysfunction in a nitroglycerin (NTG)-induced rat model of migraine.MethodsAdult male Wistar rats were injected with NTG (5 mg/kg, intraperitoneal) every second day over nine days to induce migraine. The experiments were done in the following six groups (6 rats per group) untreated control, NTG, NTG plus vehicle, and NTG groups that were post-treated with intra-BLA microinjection of Orx1R antagonist SB-334867 (10, 20, and 40 nM). Thermal hyperalgesia was assessed using the hot plate and tail-flick tests. Moreover, the elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behaviors. The animals’ sociability was evaluated using the three-chamber social task. The NTG-induced photophobia was assessed using a light-dark box.ResultsWe observed no change in NTG-induced thermal hyperalgesia following administration of SB-334867 (10, 20, and 40 nM). However, SB-334867 (20 and 40 nM) aggravated the NTG-induced anxiogenic responses in both the EPM and OF tasks. The NTG-induced social impairment was overpowered by SB-334867 at all doses. Time spent in the dark chamber of light-dark box was significantly increased in rats treated with SB-334867 (20 and 40 nM/rat).ConclusionsThe findings suggest a role for Orx1R within the BLA in control comorbid affective complaints with migraine in rats.

The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice.

Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.

Features of ozone effect on oxygen-dependent processes in the blood under hypoxic conditions

Introduction. Ozone is a physiological factor that can change hemoglobin oxygen affinity and the formation of gaseous transmitters (NO, H2S). The aim is to study the effect of ozone with gaseous transmitters donors on oxygen-dependent processes in the blood under hypoxic conditions in vitro. Materials and methods. Blood samples were divided into 6 groups of 3 ml each. Groups 2, 4, 5, 6 were pretreated with a deoxygenating gas mixture (5.5 % CO2; 94.5 % N2). In groups 3, 4, 5, 6, ozonized isotonic sodium chloride solution (with an ozone concentration of 6 mg/l) was added, and in groups 5 and 6, the donors of gas transmitters nitroglycerin and sodium hydrosulfide, respectively, were additionally introduced. Results. Pre-deoxygenation reduces the effect of ozone on oxygen transport in the blood. Nitroglycerin prevents this effect. The action of ozone under hypoxic conditions leads to an increase of content of NO3-/NO2- and H2S, and combination with nitroglycerin and sodium hydrosulfide increase these parameters. Deoxygenation due to ozone reduces parameters of lipid peroxidation (malonic dialdehyde, diene conjugates), retinol and α-tocopherol, and the same result in the nitroglycerin group. Conclusion. Under hypoxic conditions, a decrease in the effect of ozone on oxygen-dependent processes is reported. Nitroglycerin reduces its manifestation, while sodium hydrosulfide does not have a similar effect.

Milrinone is better choice for controlled low central venous pressure during hepatectomy: A randomized, controlled trial comparing with nitroglycerin

BackgroundTo explore the feasibility and effectiveness of controlled low central venous pressure(CLCVP)induced by milrinone during hepatectomy, and its influence on perioperative hemodynamics, blood loss and patients’ recovery, comparing with the traditional method by nitroglycerin. Methods52 patients who underwent elective open hepatectomy were enrolled in the study and randomly divided into two groups: milrinone (M) group and nitroglycerin (NG) group. Milrinone was infused with the rate of 0.5 μg/kg/min in group M, while nitroglycerin was given 0.2–0.5 μg/kg/min in group NG to maintain CVP≤ 5 mmHg during liver resection. The demographic variables, data of the operative procedure and intraoperative hemodynamics were recorded. The postoperative recovery profiles and pre- and post-operative haematological markers of vital organs were also collected and compared. Results1. The blood loss of group M, no matter during liver resection or in the whole procedure, was both less than that of group NG (P < 0.05), so did the hemoglobin detected by blood gas analysis (P < 0.05). Meanwhile, time of hepatectomy and hepatic hilum occlusion were shorter in group M (P < 0.05). 2. Compared with the NG group, cardiac index (CI) and stroke volume index (SVR) were higher in group M in the operation. The norepinephrine dosage necessary in the operation was of no difference in two groups (P > 0.05). 3. Drainage indwelling time and postoperative hospital stay of group M were shorter than that of group NG (P < 0.05). Most of the blood biomarkers increased on postoperative day (POD)-1, and returned to the preoperative level on POD-7 without inter-group difference (P > 0.05). Brain natriuretic peptide precursor (Pro-BNP) in group M was higher than NG group on POD-1 (P < 0.05), and the statistical difference disappeared on POD-7. ConclusionMilrinone can effectively maintain a controlled low central venous pressure during hepatectomy. Compared with nitroglycerin, milrinone can reduce the amount of blood loss, with the benefit of better manifestation of hemodynamics and enhanced postoperative recovery.

Comparing the Efficacy of 2% Diltiazem Gel with 0.2% Glyceryl Trinitrate in Anal Fissure

Objective: To compare the efficacy of 2% diltiazem gel with 0.2% glyceryl trinitrate in patients presenting with chronic anal fissure at Tertiary Care Hospital, Larkana.&#x0D; Methodology: This prospective comparative Study was conducted at department of Surgery ward-II Chandka Medical Hospital, Larkana from 14-01-19 to 14-07-19. A total of 130 patients who were treated as OPD cases were included in this study. Each patient detailed history &amp; clinical examination, details of symptomatology was recorded in a epically diagnosed proforma. These patients were randomly divided in two equal groups i-e group A 65 patients and group B 65 patients. Group A patients were treated with 02% glyceryl trinitrate and group B patients were treated with diltiazem gel 02%. All the patients of group A &amp; B were followed up to 02 months after start of leadema as a OPD cases.&#x0D; Results: A total of 130 patients (65 each in 2% diltiazem gel with 0.2% glyceryl trinitrate group) were included. Mean age in both groups was 42.56±3.91 and 41.71±4.01. 46 (70.8%) and 19 (29.2%) were male and female in Group A and 39 (60%) and 26 (40%) were male and female in Group B. Efficacy of 2% diltiazem gel with 0.2% glyceryl trinitrate in patients presenting with chronic anal fissure was 76.9% and 50.8% respectively.&#x0D; Conclusion: DTZ (2%) and GTN (0.2%) are equally effective in healing anal fissures. DTZ is better than GTN as it causes less side effects, low recurrence rate, healing rate and therefore better compliance.

Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID) After Stroke: Rationale, Design and Protocol for a Prospective Randomized Controlled Trial

Background: Despite intravenous thrombolysis and endovascular therapy for acute ischemic stroke (AIS), many survivors still have varying degrees of disability. Glyceryl trinitrate (GTN), a nitric oxide (NO) donor, has been previously reported to induce neuroprotection after AIS. The use of GTN to reduce brain damage after stroke remains yet to be elucidated. This study was designed to explore the safety, feasibility, and preliminary efficacy of intravenous administration of GTN after AIS.Methods: A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to GTN group and control group with a 1:1 ratio (n = 40). Both groups will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the GTN group will receive intravenous administration of GTN (5 mg GTN in 50 ml saline at a rate of 0.4 mg/h that is continued for 12.5 h/day for 2 days) within 24 h of symptom onset. Participants allocated to the control group will receive intravenous administration at equal capacity of 0.9% normal saline (NS) (total 50 ml/day at 4 ml/h that is continued for 12.5 h/day for 2 days). The primary outcome is safety [systolic blood pressure (SBP) <110 mmHg, headache], while the secondary outcomes include changes in functional outcome and infarction volume.Discussion: Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID) is a prospective randomized controlled trial that aims to ascertain the safety, feasibility, and preliminary efficacy of intravenous GTN as a neuroprotection strategy after AIS. These results will provide parameters for future studies as well as provide insights into treatment effects. Any possible neuroprotective qualities of GTN in AIS will also be elucidated.Trial Registration:www.chictr.org.cn, identifier: ChiCTR2100046271.

Nitroglycerin (NTG) plus whole intracranial radiotherapy for brain metastases (BM) in non-small cell cancer patient (NSCLC): A randomized open label, phase II clinical trial.

9114 Background: Hypoxia has been associated with chemo-radioresistance secondary to Vascular Endothelial Growth Factor Receptor induced by Hypoxia Induced Factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in cell lines, and this may have anti-angiogenic, pro-apoptotic, and anti-efflux effects. Particularly, EGFR mutated (EGFRm) tumor cell lines have been shown to overexpress both VEGF and HIF. In this phase II study, we evaluated the effect of transdermal NTG on intracranial objective response rate (iORR), intracranial progression-free survival (ICPFS), and overall survival (OS) of NSCLC patients with BM. Methods: We performed an open-label, phase II clinical trial among ninety-six histologically confirmed NSCLC patients with BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. iORR and ICPFS were evaluated by MRI by two independent, blinded radiologists. Nitroglycerin was administered using a transdermal 36 mg patch, which released 10 mg in 24 hours with a rest interval of 12 hours from Monday-Friday throughout WBRT administration (10 days). Results: Fifty patients were allocated to the control group, while 46 were allocated to the experimental group (NTG); among these 26 (55.3%) had EGFRm in the control group and 21 (44.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response when compared to controls (56.6% vs. 43.5%; p = 0.024). Additionally, patients who received NTG in addition to WBRT had an independently prolonged ICPFS compared with those who received WBRT alone (27.7 vs. 9.6; HR: 0.470 [95%CI: 0.24-0.89]; p = 0.021). PFS was also positively impacted (HR: 0.519 [95%CI: 0.27-0.98]; p = 0.043). The benefit in terms of iORR and ICPFS (HR: 0.38 [95%CI: 0.16-0.91]; p = 0.030) was particularly important in the EGFRm patient subgroup. No differences were observed in OS. A significantly higher rate of vomiting presented in the NTG arm of the study ( p= 0.016). Conclusions: The concurrent administration of NTG and chemo-radiotherapy improves iORR and ICPFS among NSCLC patients with BM. The benefit is particularly significant in the EGFRm patient subgroup. Clinical trial information: NCT04338867.

Myocardial protective effect of intracoronary administration of nicorandil and alprostadil via targeted perfusion microcatheter in patients undergoing elective percutaneous coronary intervention: A randomized controlled trial.

Background:The aim of the study was to evaluate the efficacy of nicorandil and alprostadil on myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI).Methods:In this prospective, single-blinded, randomized controlled study, 90 consecutive patients scheduled for elective PCI for de novo coronary lesions were assigned to the nicorandil, alprostadil, and nitroglycerin groups in a 1:1:1 ratio. Drugs were administered intracoronary via a targeted perfusion microcatheter. The primary endpoint was the thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC). Additionally, the corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), and incidence of periprocedural myocardial injury (PMI) were assessed.Results:Both nicorandil and alprostadil were significantly effective in reducing TMPFC (114.6 ± 33.7 vs 93.4 ± 30.9, P = .016; 114.3 ± 34.3 vs 94.7 ± 33.3, P = .029, respectively). Similar findings were observed in the improvement of cTFC (20.3 ± 10.5 vs 13.5 ± 5.0, P = .003; 20.2 ± 7.4 vs 15.2 ± 5.2, P = .003, respectively) and percentage of TMPG 3 (100% vs 82.8%, P = .052; 83.3% vs 96.7%, P = .196, respectively); whereas, nitroglycerin produced a limited effect on TMPFC (114.4 ± 30.9 vs 112.1 ± 31.9, P = .739), cTFC (19.4 ± 7.2 vs 19.3 ± 7.2, P = .936), and percentage of TMPG 3 (86.7% vs 86.7%, P = 1.000). No significant difference was found in the incidence of PMI (16.7% vs 16.0% vs 27.6%, P = .537), though it was comparatively lower in the nicorandil and alprostadil groups. Furthermore, the intracoronary administration of nicorandil and alprostadil had a mild effect on blood pressure and heart rate.Conclusions:The intracoronary administration of nicorandil and alprostadil via a targeted perfusion microcatheter was more effective in improving myocardial perfusion in patients undergoing elective PCI than nitroglycerin.

Effects of milrinone on cerebral perfusion and postoperative cognitive function in spine surgery: Secondary analysis of a CONSORT-compliant randomized controlled trial.

Objective:To compare the effects of milrinone, sodium nitroprusside (SNP), and nitroglycerin (NTG) on induced hypotension, cerebral perfusion, and postoperative cognitive function in elderly patients undergoing spine surgery.Methods:Sixty patients >60 years scheduled for lumbar fusion surgery were assigned to receive milrinone (group M), SNP (group S), or NTG (group N). The administration of the study drug was initiated immediately after perivertebral muscle retraction and was stopped after completion of interbody fusion. Target blood pressure was a decrease of 30% in systolic blood pressure from baseline or mean blood pressure of 60 to 65 mm Hg. The regional cerebral venous oxygen saturation (rSVO2), as a measure of cerebral perfusion, and the change in perioperative Mini-Mental State Examination (MMSE) score, as a measure of postoperative cognitive function, were assessed.Results:During the administration of the study drug, the overall and lowest intraoperative rSVO2 values were significantly higher (P = .01 and P = .01, respectively), and the duration of rSVO2 <60% was shorter in group M than in the other groups (P = .03). In group M, intraoperative rSVO2 was not different from the basal value, whereas in groups S and N, rSVO2 was significantly lower than the basal value during the administration of the study drug, but then returned to the basal value after terminating the study drug. Basal MMSE scores were comparable among the 3 groups. The MMSE score on postoperative day 5 was higher in group M than the other groups.Conclusions:Milrinone used to induce hypotension resulted in better intraoperative cerebral perfusion and postoperative cognitive function compared to SNP and nitroglycerin.

Prophylactic effect of rectal indomethacin plus nitroglycerin administration for preventing pancreatitis after endoscopic retrograde cholangiopancreatography in female patients.

Prophylactic pancreatic stent placement (PSP) and rectal indomethacin suppository are recommended to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Clinical trials on the use of nitroglycerin to reduce PEP have reached no definitive conclusion. Our study aimed to determine whether treatment with rectal indomethacin plus nitroglycerin could eliminate the need for PSP in patients. In this randomized clinical trial, patients were allocated into groups using a random number table, with each patient receiving a pre-made envelope containing their intervention prior to ERCP. The three treatment groups were: the placebo group, the indomethacin + nitroglycerin group, and the PSP group. The subjects were assessed for PEP and its severity by a panel of independent and blinded adjudicators. A total of 526 patients were eligible for inclusion. The placebo group included 176 patients, the indomethacin + nitroglycerin group included 176 patients and the PSP group included 174.A diagnosis of PEP was made in 64 (12.2%) cases. The rate of PEP in the three study groups placebo group, indomethacin + nitroglycerin group and the PSP group was 19.3%, 5.1%, and 12.1%, respectively. The risk of post-ERCP pancreatitis in the indomethacin + nitroglycerin group was 7% lower than that in the PSP. Indomethacin + nitroglycerin is superior to PSP in preventing and relieving the severity of post-ERCP pancreatitis in patients with difficult intubation. Indomethacin plus nitroglycerin can avoid the need for PSP in the prevention of post-ERCP pancreatitis. Current Controlled Trials ChiCTR2000033944.

Efficacy of Glyceryl Trinitrate Ointment for Perianal- Intrarectal Local Anesthesia in Transrectal Ultrasound- Guided Prostate Biopsy- Compared to Topical Lignocaine

Objective: Anorectal pain and discomfort during transrectal ultrasound (TRUS)-guided prostate biopsy is an important issue of this procedure. Therefore present study was designed to compare whether the use of topical glyceryl trinitrate (GTN) ointment or lignocaine gel is more effective as an adjunct to periprostatic nerve block (PPNB) in reducing pain associated with transrectal ultrasound (TRUS)-guided prostate biopsy. Methods: In all, 120 consecutive patients having their first TRUS-guided prostate biopsy were randomized to receive either 0.4% GTN ointment or 2% lignocaine gel, 10 minutes or 5 minutes respectively before biopsy. All patients had a biopsy preceded by an injection with 5 ml of 2% lignocaine local anaesthesia. Results: A 100-point visual analogue score was used to record overall pain due to the presence of the probe, the biopsy itself and pain after the procedure. There was no significant difference in age, PSA level and prostate volume between the groups. There was a significantly lower mean pain score due to probe insertion, in the GTN than lignocaine group (18.32 vs 37.48, P &lt; 0.001); pain perception was lower for the whole procedure in the GTN group (16.59 vs 35.17, P &lt; 0.001); and was most pronounced in men aged d”65 years (21.45 vs 40.7, P &lt; 0.001). Five patients (8.3%) in the GTN group complained of headache. Conclusion: So it can be concluded that, topical GTN ointment is safe and effective in reducing the discomfort and pain associated with TRUS-guided prostate biopsy, in particular the insertion of the ultrasound probe. It might be of maximum benefit in the younger patient(d”65years). Bangladesh Journal of Urology, Vol. 21, No. 1, January 2018 p.14-19

EFFICACY OF NITROGLYCERINE INFUSION VERSUS SUBLINGUAL NIFEDIPINE IN SEVERE PRE-ECLAMPSIA

Background: Pre-eclampsia is a pregnancy-specific syndrome of reduced organ perfusion secondary to vasospasm and endothelial activation. The incidence of preeclampsia is estimated to range between 2.5 and 5%. An accurate estimate, as well as its global burden, is difficult to obtain, due to lack of data from several countries and standardization of diagnostic criteria. Objective: To compare between the uses of continuous i.v. administration of nitroglycerine versus sublingual nifedipine in the management of women with severe pre-eclampsia who were being managed with controlled plasma volume expansion and MgSO4 loading and maintenance doses. Patients and Methods: Patients were taken from Sayed Galal Hospital. This study was carried out on 100 women with severe pre-eclampsia who were being managed with controlled plasma volume expansion and MgSO4 loading and maintenance doses. Those women were randomly assigned into two equal groups: Nitroglycerine or nifedipine. Both groups were compared as regard maternal adverse effects of vasodilator therapy, mean arterial pressure changes within one hour after vasodilator therapy, post therapy changes in fetal cardiotocography (CTG) and for feto-maternal complications including gestational age of termination of pregnancy, time of maternal intensive care unit (ICU) stay and the need of neonatal ICU. Results: Statistical analysis of the magnitude and time course of maternal hypotensive responses after initiation of the vasodilator therapy showed that, in nitroglycerine group, a statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) started just 5 min. after the initiation of nitroglycerine infusion, while in nifedipine group, the significant decrease in SBP and DBP started 15 min. after oral nifedipine. The SBP and DBP measurements in nitroglycerine group were significantly lower than those in nifedipine group. The feto-maternal safety margin observed was similar in the two study groups. Conclusion: IV infusion of nitroglycerine was effective, safe and alternative therapy for severe pre-eclampsia.

Comparison of Labetalol, Nitroglycerine and High Dose Propofol for Induced Hypotension in Functional Endoscopic Sinus Surgery in Massive Nasal Polyposis: A Randomized Trial

Background: Objective: The aim of this study was to assess the quality of the surgical field, amount of blood loss, and duration of surgery following induced hypotension with labetalol, nitroglycerin, and high dose propofol in patients undergoing FESS under general anesthesia. Methods: One hundred and eight patients scheduled for FESS under general anesthesia were recruited in this randomized trial and were allocated to one of the three study groups: 1) Nitroglycerine (NTG) group: nitroglycerine with a dose of 2-5 μg/kg/min was administered; 2) Labetalol (LAB) group: an IV bolus dose of labetalol (20 mg) was injected at first and then IV infusion of labetalol at a rate of 1-2 mg/min; 3) High dose propofol plus normal saline (0.5-1 ml/min) group. Hemodynamic variables and the amount of bleeding were recorded intraoperatively and the surgeons' satisfaction was asked following each surgery considering the surgical field quality using a 5-item Likert scale. Results: The average blood loss (ml) in patients in the LAB group was significantly less than patients in NTG and high dose propofol groups (127 ml vs 198 and 145 ml, respectively) (p- value=0.001) and the surgeons expressed greater satisfaction with the surgical field quality in the LAB group (p- value=0.001). Conclusion: Labetalol infusion may be a safe and effective method for induction of controlled hypotension to provide a comparatively bloodless field. High dose propofol may be a second choice if labetalol is not available.