Nitroglycerin Group Research Articles

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

BackgroundRodent 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. New methodRats 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. ResultsAnimals 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. Comparison with existing methodsMost 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. ConclusionsThis 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.

Efficacy of nitroglycerine ointment in the treatment of pediatric anal fissure

BackgroundAnal 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. Patients and methodsAn 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. ResultsThe 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. ConclusionThe 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. Type of studyProspective randomized controlled study (treatment study). Level of evidenceType 2.

The effect on myocardial perfusion and clinical outcome of intracoronary nicorandil injection prior to percutaneous coronary intervention in ST-segment elevation myocardial infarction

Objective: To investigate the effect of intracoronary administration of nicorandil prior to primary percutaneous coronary intervention (PPCI) on myocardial perfusion and short-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 158 patients with STEMI undergoing PPCI from January 2014 to December 2015 in Fuzhou General Hospital were enrolled consecutively in this prospective controlled randomized trial. Patients were assigned into three groups with random number table: the nicorandil group (patients received intracoronary administration of 6 mg nicorandil after guide wire or balloon successfully crossed the target lesion, n=53), the nitroglycerin group (patients received intracoronary administration of 300 μg nitroglycerin after after guide wire or balloon successfully crossed the target lesion, n=52) and the control group(patients received routine treatment, n=53). The primary outcomes were myocardial perfusion, including the levels of corrected TIMI frame count (cTFC), and the incidence of no reflow or slow flow after PPCI. The secondary outcomes included the incidence of major adverse cardiovascular events (MACE) during hospitalization (all-cause death, reperfusion arrhythmia within 2 hours after PPCI, angina within 24 hours after PPCI, new heart failure or worsening cardiac function, and repeat revascularization) and within 3 months of follow-up (all-cause death, nonfatal myocardial infarction, repeat revascularization, post-infarction angina, and re-hospitalization for congestive heart failure). Results: The age of enrolled patients was (62.9±11.3) years old, and 130 cases (82.3%) of them were male. The median time of symptom-onset to balloon was 4.50 (3.20, 6.43) hours. There were significantly difference in cTFC immediately after PPCI((21.68±7.43)frames, (24.74±8.66)frames, and(27.06±10.40)frames), incidence of no reflow or slow flow after PPCI(5.7%(3/53), 13.5%(7/52), and 22.6%(12/53)), ST-segment resolution at 2 hours after procedure(90.6%(48/53), 84.6%(44/52), and 74.5%(38/53)), and reperfusion arrhythmia at 2 hours after procedure(15.1%(8/53), 36.6%(19/52), and 34.0%(18/53)) among the 3 groups(P<0.01 or 0.05). In the multivariate logistic regression models, intracoronary administration of nicorandil could lower the cTFC level (OR=0.17, 95%CI 0.10-0.41, P=0.001), acted as a protecting factor on lowering the incidence of no reflow or slow flow (OR=0.13, 95%CI 0.02-0.96, P=0.045) and reperfusion arrhythmia (OR=0.26, 95%CI 0.09-0.74, P=0.012), as well as facilitating the ST-segment resolution at 2 hours after procedure (OR=4.62, 95%CI 1.14-18.82, P=0.033). However, observed parameters were similar between intracoronary administration of nitroglycerin group compared with control group (all P>0.05). MACE within 3 months of follow-up were similar among the 3 groups(all P>0.05). Conclusion: Intracoronary administration of nicorandil prior to balloon dilation can significantly improve the myocardial perfusion and reduce the occurrence of reperfusion arrhythmia during PPCI for STEMI, but does not affect the short-term prognosis in STEMI patients.

Sublingual glyceryl trinitrate during colonoscopy and terminal ileal intubation: a randomized controlled trial.

Background and aims Sublingual glyceryl trinitrate has been used as an aid to cannulate the Sphincter of Oddi during endoscopic retrograde cholangiopancreatography. Its role in terminal ileal intubation during colonoscopy is unknown. This study examines the role of sublingual glyceryl trinitrate in terminal ileal intubation during colonoscopy. Methods A triple-blind randomized controlled trial comparing sublingual glyceryl trinitrate (800 µg) vs. placebo (saline) in relation to terminal ileal intubation during colonoscopy was performed. Following caecal intubation, participants received sublingual glyceryl trinitrate/placebo followed by a 2-min observation period before intubation was attempted. Data on time to intubate the terminal ileum and intubation rate were collected. Results A total of 110 patients (age: 58 years (18-75)) were recruited and randomised as per protocol: 54 received sublingual glyceryl trinitrate. Terminal ileal intubation was successful in all patients receiving sublingual glyceryl trinitrate and in 53 (94.6%) of those receiving saline ( p = 0.243: Fischer's exact). The median time taken for ileal intubation after application of spray was 72.5 (7-900) s in the glyceryl trinitrate group compared with 125 (5-900) s in the placebo group ( p = 0.150: Mann-Whitney). There were no major adverse events reported in either group. Conclusions Terminal ileal intubation rates and timing were very good in both groups. Routine sublingual glyceryl trinitrate was not proven to be beneficial in improving terminal ileal intubation or intubation success rates in the hands of experienced colonoscopists. However, trends in this small study might suggest that glyceryl trinitrate could be useful in the hands of less experienced colonoscopists or in difficult terminal ileal intubation cases.

Comparison of hemodynamic effects of inhaled milrinone and inhaled nitroglycerin in patients with pulmonary hypertension undergoing mitral valve surgery

Introduction Pulmonary hypertension (PH) frequently complicates the perioperative management of patients undergoing mitral valve surgery and has been shown to be a significant independent predictor of postoperative morbidity and mortality. The aim of this work is to compare the effects of inhaled milrinone and inhaled nitroglycerin on pulmonary and systemic hemodynamic responses in patients with PH undergoing mitral valve surgery. Patients and methods A total of 50 patients with PH were randomly divided into two groups with 25 patients in each group: group I patients received inhaled nitroglycerin (5 mg, 1 mg/ml) over 15 min and group II patients received inhaled milrinone (5 mg, 1 mg/ml) over 15 min through an ultrasonic nebulizer connected to the inspiratory limb of the ventilator circuit near the endotracheal tube immediately after separation from cardiopulmonary bypass. Hemodynamic parameters were measured after induction of anesthesia (T1), immediately after the end of cardiopulmonary bypass (T2), 30 min after the start of treatment, and 90 min after the start of treatment (T4). The hemodynamic variables were as follows: heart rate, mean arterial blood pressure (MAP), mean pulmonary artery blood pressure (MPAP), cardiac index (CI), systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), and right ventricular stroke work index (RVSWI). Results At 30 min after the start of treatment, both groups showed a significant comparable decrease in MPAP, PVRI, and RVSWI, with no significant changes in MAP, CI, and SVRI. At 90 min after the start of treatment, MPAP, PVRI, and RVSWI returned to their values in the inhaled nitroglycerin group but remained at significantly lower values in the inhaled milrinone group. Conclusion Inhalation of nitroglycerin and milrinone produces a comparable decrease in MPAP, PVRI, and RVSWI without significant changes in heart rate, MAP, CI, and SVRI. Inhaled milrinone has a longer duration of action than inhaled nitroglycerin.

The clinical course of atrial fibrillation in patients with coronary heart disease

To elucidate evolution of the clinical course of AF in patients with CHD in a long-term prospective study. The study included. 112 patient aged 57-74 (mean 67.44±3.3) years with CHD and paroxysmal form of AF carried outfrom 2011 to 2015. Evolution of the clinical course of AF was evaluated based on the number of arrhythmic attacks during the last 3 months. The appearance of prolonged persistent AF episodes or permanent AF was regarded as progression of arrhythmia. During the 4 year study, 64 (57,2%) patients (group 1) did not experiencea rise in the frequency and duration of AF attacks. Progression of arrhythmia was documented in 48 (42,8%) of the 112 (100%) patients (group 2). These patients more frequently had the history of myocardial infarction and chronic heart failure than patients of group 1. The latter had the mean values of left ventricular (LV) ejection fraction 61,23±6,24%, i.e. significantly higher than 48,47±8,4% in group 2.47 and 28 % of the patients in group 2and 1 respectively suffered mitral regurgitation (p<0,05). Patients of group 2 had significantly more akineticzones. Intake of nitroglycerin in group 1 resulted in positive dynamics of local LV contractility that did not change in patients of group 2. 42,8% of the patients with CHD and paroxysmal form of AF experienced progression of arrhythmia into a persistent or permanent form. Predictors of AF progression in patients with CHD are the history of myocardial infarction, chronic heart failure, mitral regurgitation, and irreversible changes in local myocardial LV contraction.

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

BackgroundPrevious 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. MethodsThe 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. ResultsThe 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. ConclusionIntravenous nicorandil increased renal artery blood flow velocity in comparison with nitroglycerin. Nicorandil has a significant effect on renal hemodynamics.

OS 31-01 BLOOD PRESSURE, INITIAL ORTHOSTATIC HYPOTENSION, GLYCERYL TRINITRATE AND THE GLU504LYS POLYMORPHISM OF ALDEHYDE DEHYROGENASE-2

OBJECTIVE: Glyceryl trinitrate (GTN) is used to treat angina and lower blood pressure. The enzyme mitochondrial aldehyde dehydrogenase-2 (ALDH2) can activate GTN. The polymorphism (Gly504Lys) in the gene encoding ALDH2 is associated with significantly reduced enzyme activity and potentially diminished responses to GTN. DESIGN AND METHOD: Systolic blood pressure (SBP) was measured continuously (Finometer Midi) during 2 orthostatic challenges in 493 healthy young adults (mean age 22 y), 390 of whom took 300 μg GTN sublingually 5 min prior to the second challenge and 103 subjects of whom were untreated. We recorded the average SBP for 30 s after 5 minutes lying, the nadir in SBP within 30 s of standing and the average SBP for 30 s after 2 minutes standing. The ALDH2 polymorphism was measured by the SNP rs671 (allele A = Lys, allele G = Gly). A dominant model (GG v AG/AA) was use to compare SBP with adjustments for age, sex and weight. RESULTS: During the control challenge in the GTN group, the mean lying SBP was 117 mmHg (SD 15.8), 73 mmHg (20.4) on initial standing and 109 mmHg (16.9) after 2 minutes standing. After GTN, SBP was significantly (all P < 0.0001) lower than control lying [114 mmHg (15.9)], on standing [60 mmHg (19.3)] and after 2 minutes standing [103 mmHg (16.9)]. In the 103 untreated subjects there were no significant differences between the SBP between challenges. None of the SBP responses after GTN differed between the 2 ALDH2 genotype groups. CONCLUSIONS: In healthy young adults acute GTN causes a major exaggeration of the initial orthostatic hypotension within 30 s of standing. The hypotensive actions of GTN were not associated with the Gly504Lys polymorphism. These findings suggest that factors other than ALDH2 activity explain the blood pressure effects of acute exposure to GTN.

Randomized clinical trial of the use of glyceryl trinitrate patches to aid arteriovenous fistula maturation.

Arteriovenous fistulas are critical for haemodialysis, but maturation rates remain poor. Experimental and anecdotal evidence has supported the use of transdermal glyceryl trinitrate (GTN) patches. The aim of this RCT was to determine whether use of a GTN patch aids arteriovenous fistula maturation. Patients referred for arteriovenous fistula formation were eligible. The GTN or placebo patch was applied immediately after surgery and left in situ for 24 h. The primary outcome measure was the change in venous diameter at 6 weeks after fistula formation. The secondary outcome measure was clinical fistula patency at 6 weeks. Of 200 patients recruited (533 screened), 101 were randomized to the placebo group and 99 to the GTN group. Of these, 81 and 86 respectively completed surgery, and had follow-up data available at 6 weeks. Improvements in venous diameter were similar in the two groups: mean(s.d.) increase 2·3(1·9) mm in the placebo group compared with 2·2(1·8) mm in the GTN group (P = 0·704). The fistula failure rate did not differ significantly between the two groups: 23 per cent for placebo and 28 per cent for GTN (P = 0·596). GTN transdermal patches used for 24 h after surgery did not improve arteriovenous fistula maturation. NCT01685710 (http://www.clinicaltrials.gov).

Effects of Zhengtian Pills on Migraine Headache in Rats via Transient Receptor Potential Vanilloid 1

ObjectiveTo investigate the effects and molecular mechanism of Zhengtian Pills (ZTP) on migraine headache. MethodsAll rats were randomly divided into control, positive control, migraine model, low- and high-dose ZTP groups, and glyceryl trinitrate was injected to induce migraine headache. The time of ears turning red, frequency of scratching head, climbing the cage, and head-twitching were used to evaluate rat behaviors. After 10 d administration of ZTP, the expression levels of transient receptor potential vanilloid 1 (TRPV1) both in cortex and hippocampus were determined by Western blotting. ResultsAfter 2 min of glyceryl trinitrate injection, rats showed headache phenomena that parallels the clinical symptoms of migraine, which peaked in 30 min, and lasted for 60 min. Frequency of head-twitching and numbers of scratching head in glyceryl trinitrate (GTN) group were significantly increased. In contrast, after ZTP (1.08 g/kg, ig) treatment, the numbers of scratching head with fore-limb, hind-limb and the frequency of head-twitching were significantly decreased. Flunarizine (FLU) and low-dose ZTP (0.54 g/kg) also showed a trend to decrease the numbers of scratching head and head-twitching frequency, but no significant difference. Besides, ZTP significantly decreased the up-regulated TRPV1 protein expression level both in cortex and hippocampus. ConclusionThe present study shows that ZTP could significantly improve the migraine symptoms of headache in rats and TRPV1 might be one of the important molecular mechanisms. This is the first report about the effect of ZTP on TRPV1 protein expression level both in cortex and hippocampus of rats.

Intravenous loading of nitroglycerin during rewarming of cardiopulmonary bypass improves metabolic homeostasis in cardiac surgery: a retrospective analysis.

The aim of the study was to evaluate the effects of high-dose nitroglycerine (NTG) on glucose metabolism, tissue oxygenation and postoperative recovery in cardiac surgical patients. Cardiac surgical patients in the retrospective survey were classified into two groups based on the NTG regimen. NTG group had intravenous loading of NTG (infusion rate 10-20mg/h with total dose of ≥0.5mg/kg) starting at rewarming of cardiopulmonary bypass (CPB) (n=101), and control group had no intravenous loading of NTG (n=151). Data for intraoperative plasma glucose and lactate levels, and regular insulin consumption were collected. Propensity score methodology was utilized to adjust for potential confounders. After adjustment for propensity score, the plasma glucose was significantly lower in the NTG group during (161±39 versus 179±45mg/dl, p=0.005) and after CPB (167±41 versus 184±48mg/dl, p=0.012). Total consumption of regular insulin was significantly lower in the NTG group, median 8 (range 0-50) versus 13 (0-90) international units, p=0.005. There was a trend towards statistical significance in a lower incidence of hyperlactatemia (>2.2mmol/l) in the NTG group during CPB, 21/100 (21%) versus 40/132 (30.3%), p=0.065. The mixed venous oxygen saturation in the intensive care unit was higher in the NTG group, 65±9 versus 62±11%, p=0.056. Intravenous loading of NTG during and after CPB is safe and effective for attenuating the hyperglycemic response and reduce the incidence of hyperlactatemia during cardiac surgery with CPB.

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

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.

Evaluation of analgesic effect of nitroglycerine added to lignocaine in intravenous regional anesthesia

Background: In this study, we used nitroglycerine (NTG) as an adjuvant to lignocaine in intravenous regional anesthesia (IVRA) to enhance the analgesic property of lignocaine. Aim: To evaluate the effect of addition of NTG to lignocaine in IVRA. Objective: To find out the onset, duration, and requirement of postoperative analgesics with the addition of NTG. Materials and Methods: This was a randomized (block randomization), double-blinded, placebo-controlled study of 60 patients of the American Society of Anesthesiologists Class I and II, undergoing hand and forearm surgeries. Patients received IVRA with 3 mg/kg 2% lignocaine diluted to a total volume of 40 ml to which either 150 μg NTG or equal volume of saline was added. Intraoperatively and postoperatively, pain score was evaluated using visual analog scale. The sensory and motor block onset and recovery time and the subsequent analgesic requirement in first 24 h were recorded. Results: Motor and sensory block onset time were significantly shorter (P < 0.001), and motor and sensory block recovery time were prolonged (P < 0.001) in NTG group compared to plain lignocaine group. Intra-operatively fentanyl requirement was significantly lower and quality of sensory and motor blockade was better in study group than control group (P < 0.001). In addition, patients in NTG group required significantly less number of analgesics in the first 24 h as compared to the other group. Nitrates are potent relaxers of vascular smooth muscles and act by dilating veins, arteries, and arterioles. In IVRA, most of the anesthetic agent is absorbed into the limb tissue. Thus, the local anesthetic agent reaches to the nerves and nerve endings quickly. Thus shortens the onset time and also prolongs sensory and motor blockade and reduces total analgesic consumption in first 24 h without significant side effects. Conclusion: NTG as an adjuvant to lignocaine for IVRA reduces the total analgesic consumption in first 24 h and improves sensory and motor block without side effects.

Attenuation of pressor response following intubation: Efficacy of nitro-glycerine lingual spray.

Background and Aims:The role of nitro-glycerine (NTG) lingual spray for attenuation of the hemodynamic response associated with intubation is not much investigated. We conducted this study to evaluate the efficacy of NTG lingual pump or pen spray in attenuation of intubation induced hemodynamic responses and to elucidate the optimum dose.Material and Methods:In a prospective randomized controlled trial, 90 adult patients of ASA I, II, 18-60 year posted for elective general surgery under general anesthesia with intubation were randomly allocated to three groups as Group C (control) - receiving no NTG spray, Group N1 – receiving 1 NTG spray and Group N2 – receiving 2 NTG spray one minute before intubation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate were recorded at baseline, just before intubation (i.e., 60 s just after induction and NTG spray), immediately after intubation, at 1, 2, 5 and 10 min after intubation.Results:Incidence of hypertension was significantly higher in Group C (60%, n = 18) as compared to Group N1 and N2 (10%, n = 3 each), P < 0.01. Mean value of SBP, DBP and MAP showed a significant rise as compared to baseline, following intubation in control group (15.31% in SBP, 12.12% in DBP, 17.77% in MAP) that persisted till 5 min, while no significant rise was observed in Group N1 and N2. There was a trend toward fall in blood pressure in Group N2 (4.95% fall in SBP, 4.72% fall in MAP) 1-min following spray, which was clinically insignificant. Mean value of SBP, DBP and MAP was significantly higher in Group C than in Group N1, which was in turn greater than Group N2 (Group C > N1> N2), P < 0.05. However, incidence of tachycardia was comparable in three groups (70% in group C, 63.33% in Group N1 and 67.77% in Group N2, P > 0.05).Conclusions:We concluded that the NTG lingual spray in dose of 0.4 mg (1 spray) or 0.8 mg (2 sprays) was effective in attenuation of intubation induced hemodynamic response, in terms of preventing significant rise in SBP, DBP and MAP compared to control group.

AN AGGRESSIVE APPROACH TOWARDS TREATMENT OF ACUTE ANAL FISSURE

Objective: To evaluate the efficacy of 0.2% glyceryl trinitrate (GTN) paste as first line treatment in acute anal fissure with no severe side effects. Study Design: Randomized control trial.Place and Duration of Study: Combined Military Hospital Kharian and Combined Military Hospital MalirPakistan from January 2008 to August 2010.Patients and Methods: Patients presenting with acute anal fissure were randomized in 2 groups by using computer generated table. Group A received 0.2% GTN paste and group B received lignocaine gel twice daily in addition to high fiber diet, sitz bath and stool softeners. Pain scores on 100 mm Visual Analogue Scale, healing of fissure and side effects (headache and flatus incontinence) were noted at 0,2,4,6 and 8 weeks. Evolution to chronic anal fissure and recurrence rates (3 and 6 months) was also noted. Data was entered on SPSS 16.0 and p value was calculated. Results: Out of 161 patients, 109 patients (56 in group A and 53 in group B) completed the study. Demographical data was comparable in both the groups. Results were statistically significant (p &lt;0.05 or less) in terms of complete healing of fissure and pain relief at each visit. Patient in group A had less recurrence Conclusion: Use of 0.2% GTN as first line treatment in acute anal fissure showed better pain relief fastened healing, less rec

Effect of Glyceryl Trinitrate Ointment on Pain Control After Hemorrhoidectomy: A Meta-analysis of Randomized Controlled Trials.

Hemorrhoidectomy is associated with postoperative pain and prolonged wound healing. Glyceryl trinitrate has been shown to decrease muscle spasm and increase anodermal blood flow. A meta-analysis of randomized controlled trials was conducted to evaluate the efficacy of topical glyceryl trinitrate application in pain relief after hemorrhoidectomy. PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov registries were searched for studies published before August 2015. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate a pooled effect size using random effects models. Pain was assessed using a visual analog scale on days 1, 3, 7, and 14 after operation. Secondary outcomes included time taken to resume routine activities, wound healing at 3 weeks after operation, complication, and headache incidence. A total of 12 trials with 1095 patients were reviewed. Significant pain reduction was observed on days 1, 3, 7, and 14 after hemorrhoidectomy in the glyceryl trinitrate groups. Glyceryl trinitrate-treated patients appeared to resume routine activities earlier than those in the control group (weight mean difference -7.52; 95% confidence interval: 16.13-1.08). The wound healing rates 3 weeks after operation were significant higher in the glyceryl trinitrate-treated groups than in the control group (risk ratio 1.79; 95% confidence interval: 1.38-2.33). However, the incidence of headache significantly increased in the glyceryl trinitrate group (risk ratio 3.68; 95% confidence interval: 1.62-8.34). Topical application of glyceryl trinitrate effectively relieves pain and promotes wound healing after hemorrhoidectomy; however, the substantial headache incidence may limit extensive application.

Effects of pretreatment with recombinant human B-type natriuretic peptide on infarct size in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

To investigate whether the administration of recombinant human B-type natriuretic peptide (rhBNP) before primary percutaneous coronary intervention (PCI) could further limit the infract size, improve left ventricular function, and alleviate cardiac dilation in patients with acute ST-segment elevation myocardial infarction(STEMI). A total of 93 consecutive patients presenting chest pain within 12 hours from the onset, suspicious of first STEMI located at anterior wall undergoing primary PCI, were eligible for enrollment and randomly assigned to either rhBNP group (rhBNP administration starting at 5 min before PCI, 1.5 µg/kg bolus intravenous injection followed by 0.007 5-0.03 µg·kg(-1)·min(-1) for up to 120 hours, n=48) or nitroglycerin (NIT) group (NIT treatment starting at 5 min before PCI, 10-100 µg/min intravenous infusion for 120 hours, n=45). Primary PCI was performed in both groups using post-conditioning (PC) technique. TIMI flow grade, corrected TIMI frame count, and TIMI myocardial perfusion grade were compared between the two groups at the time of infarct related artery (IRA) re-patency. The levels of serum creatine kinase MB isoenzyme (CK-MB) and troponin I (TnI) were measured. Echocardiography was performed at baseline 7 days and 6 months later. Baseline characteristics were similar between the two groups. The percentage of TIMI grade 3 and TIMI myocardial perfusion grade 3 after PCI both tended to be higher in rhBNP group than those in NIT group (95.8%(46/48) vs. 86.7%(39/45), P=0.162) and (72.9%(35/48) vs. 62.2%(28/45), P=0.500). The corrected TIMI frame count was significantly decreased in rhBNP group (21.0±8.7 vs. 28.2±14.8, P=0.005). The myocardial infarct size expressed as the AUC of CK-MB ((3 249±1 101) U/L vs. (4 474±1 661)U/L, P=0.010) or AUC of TnI ((3 670±942) µg/L vs. (4 541±1 098) µg/L, P=0.021) was significantly decreased in rhBNP group compared with those in NIT group. At 7 days after primary PCI, the left ventricular ejection fraction (LVEF) tended to be higher (P>0.05), while the E/e' index and wall motion score index (WMSI) ((11.95±3.31 vs. 14.60±4.09, P=0.030) and (1.74±0.17 vs. 2.40±0.55, P<0.001)) were significantly improved in rhBNP group compared with those in NIT group. BNP level was also significantly lower in rhBNP group compared that in NIT group ((68.3±37.8) ng/L vs. (129.4±64.4) ng/L, P<0.001). During 6-month follow-up, LVEF and WMSI were significantly improved in rhBNP group compared those in NIT group(51.7%±12.7% vs. 46.9%±9.6%, P=0.024 and 1.69±0.35 vs. 1.92±0.47, P=0.020). Administration of rhBNP before PCI with post-conditioning procedure can further improve myocardial perfusion, limit myocardial infarct size, ameliorate cardiac dysfunction and postpone left ventricular early-stage and long-term remodeling in STEMI patients undergoing primary PCI.

A Multicenter, Randomized, Trial Comparing Urapidil and Nitroglycerin in Multifactor Heart Failure in the Elderly

Multifactor heart failure is a common life-threatening event in elderly patients and often complicated by concomitant hypertension and diabetes mellitus (DM). The aim of this study was to evaluate whether α1-blocker, urapidil, provides additional therapeutic benefits compared to nitroglycerin (NG) in treatment of multifactor heart failure complicated by hypertension and DM in elderly patients. Seventy-two elderly consecutive patients were randomized into 2 groups that received treatment with urapidil or NG. All patients were monitored for blood pressure (BP) and heart rate and received tests for metabolic activity and cardiovascular function. Patients receiving urapidil had significantly lower systolic BP than their counterparts in NG group (P < 0.05). Moreover, patients in urapidil group showed lower N-terminal pro-B-type natriuretic peptide levels but higher ejection fraction (t = 2.206, P < 0.05), cardiac index (t = 3.13, P < 0.05) and left end-diastolic volume (t = -3.104, P < 0.05) compared to NG group. Although both urapidil and NG decreased fasting plasma glucose (FPG) levels, there was no significant difference of FPG levels between these 2 groups. Urapidil demonstrated better efficacy than NG on lowering and stabilizing systolic BP, attenuating cardiac afterload and improving cardiac function. Both NG and urapidil significantly reduced FPG levels in multifactor heart failure patients with DM. Urapidil is a therapeutic option for the multifactor heart failure patients complicated with hypertension and DM.

Glyceryl trinitrate for the treatment of preterm labor.

This study was conducted to compare the tocolytic efficacy of glyceryltrinitrate (GTN) with that of magnesium sulfate (MgSO4) and to investigate serum nitric oxide metabolites before and after tocolysis. In total, 48 women between 27 and 34 weeks' gestation with threatened preterm labor and intact membranes were randomly allocated to receive either GTN or MgSO4 tocolysis. Main outcome measures included tocolytic efficacy and maternal side effect(s) of the tocolytic agent. Obstetric and neonatal outcomes as well as pretreatment and posttreatment nitric oxide (NO) metabolites were assessed. Forty-one patients were included into the final analysis. Uterine contraction cessation times were 3.66±1.28 and 6.83±3.47 hours for GTN and MgSO4 groups, respectively. Similarly, maternal side effects were significantly lower in the GTN group than in the MgSO4 group, and no serious maternal side effects were recorded. Serum NO metabolite levels before treatment were significantly lower in the treatment groups than in the controls. Serum nitrite levels were significantly increased after tocolytic treatment both in MgSO4 and GTN groups. GTN effectively delays preterm delivery and reduces neonatal morbidity and mortality with less maternal side effects and seems to be an effective and safe alternative to MgSO4.

The Effects of Nitroglycerine on Pain Control During the Propofol Injection; a Controlled, Double-Blinded, Randomized Clinical Trial.

Background:The use of Propofol often results in pain upon injection, which is sometimes very distressing for patients. Many patients report some degree of pain or discomfort on injection with propofol. Injection-induced pain during induction of anesthesia can result in patient's discomfort.Objectives:This study was performed to evaluate the effects of nitroglycerine on pain severity in patients undergoing propofol injection.Patients and Methods:In this double-blind randomized clinical trial, 100 patients with ASA class I and II undergoing anesthesia with propofol injection were selected for the study from 2012 to 2013 in Imam Reza training hospital. Patients were randomly assigned to case and control groups and received either 20 μg of nitroglycerine or normal saline as placebo. The severity of injection pain was assessed using a four-point scale. An anesthesiologist observed hemodynamic and local adverse effects.Results:The pain severity in nitroglycerine group was significantly lower compared with the placebo group (P < 0.0001). Moreover, the local adverse reactions were observed only in three patients in the placebo group while no patient in the drug group experienced adverse effects (P = 0.242). The systolic blood pressure showed no significant difference between two groups before and after the induction of anesthesia but the diastolic blood pressure and the heart rate was significantly different between study groups.Conclusions:Nitroglycerine may be a safe and effective adjuvant therapeutic for pain reduction in patients under propofol injection. Hence, its use for reduction of propofol injection-induced pain is recommended.