Sublingual Nitrate Research Articles

Nitrate-Induced Headache Response in Patients with Coronary Artery Disease and Coronary Artery Ectasia: A Retrospective Case-Control Study

Abstract Background: Coronary artery ectasia (CAE), while being considered a variant of atherosclerosis, harbors distinct features that significantly differ from atherosclerosis in terms of pathophysiological mechanisms. On the other hand, headache appears to be the most common side effect of nitrates that have been used traditionally for decades. In this context, we aimed to compare the frequency and temporal characteristics of nitrate-induced headache (NIH) between subjects with sole coronary artery disease (CAD) and subjects with CAD and coexisting CAE. Materials and Methods: Two hundred and forty-four patients who had undergone coronary angiogram (CAG) and received a single dose of sublingual isosorbide dinitrate during the procedure comprised in this retrospective study population. CAG is performed in the indications due to guidelines. All patients who had undergone CAG were held under close supervision, at least, for 6 h following CAG (and administration of sublingual nitrate); duration and emergence time of NIH were recorded for all patients. Of these 244 patients, 225 patients having sole CAD were assigned to Group I, whereas 19 patients having both CAD and CAE were assigned to Group II. Results: NIH was observed in 19 out of 225 patients (8%) with sole CAD and in 9 out of 19 patients (56%) with CAD and CAE (P = 0.003). The mean interval between the administration of sublingual isosorbide dinitrate and NIH onset was significantly lower in Group II in comparison to Group I (44 ± 14 min vs. 87 ± 63 min, respectively, P = 0.018). However, the duration of NIH was comparable between the two groups (Group I: 203 ± 53 min vs. Group II: 173 ± 61 min, P = 0.24); logistic regression analysis revealed an independent association between NIH and CAE (odds ratio: 11.5, 95% confidential interval: 3.9–33.8, P < 0.001). Conclusion: We have demonstrated that sublingual nitrates might induce NIH more frequently in subjects with CAE and CAD in comparison to those with sole CAD. Furthermore, NIH has been demonstrated to be independently associated with CAE.

Nontopical Nitrates in Flap Perfusion and Delay Phenomenon.

Topical nitrates have demonstrated efficacy in improving flap perfusion. However, evidence for nontopical nitrates in modulation of flap perfusion dynamics has yet to be consolidated. Here, we review evidence regarding the use of intravascular, sublingual, and oral nitrates in modulating flap perfusion. We performed a review of the literature for evidence linking nontopical nitrates and flap perfusion, and included clinical studies, animal studies, and in vitro studies. Evidence suggests that intravascular, sublingual, and oral nitrates exert vasodilatory properties, which may be harnessed for identification of perforators and improved flap perfusion. We also found evidence suggesting nitrates may facilitate ischemic preconditioning while reducing ischemia-reperfusion injury. Nitrates delivered intravascularly, sublingually, or orally may increase flap perfusion and serve as a method for ischemic preconditioning, particularly in the intraoperative setting.

Anti-Anginal Efficacy of Zibotentan in the Coronary Slow-Flow Phenomenon.

Patients with coronary microvascular disorders often experience recurrent angina for which there are limited evidence-based therapies. These patients have been found to exhibit increased plasma levels of endothelin; thus, selective endothelin-A (Et-A) receptor blockers such as zibotentan may be an effective anti-anginal therapy in these patients. The study evaluated the impact of a 10 mg daily dose of zibotentan on spontaneous angina episodes in patients with the coronary slow-flow phenomenon who had refractory angina (i.e., experiencing angina at least three times/week despite current anti-anginal therapy). Using a randomized, double-blind, placebo-controlled, crossover trial design with 4-week treatment periods, 18 patients (63.2 ± 9.9 years, 33% females) were recruited. The primary endpoint was angina frequency as measured by an angina diary, with secondary endpoints including nitrate consumption, angina duration/severity and the Seattle Angina Questionnaire (SAQ) domains. During the 4 weeks of therapy, angina frequency significantly improved with zibotentan therapy (placebo 41.4 (58.5) vs. zibotentan 29.2 (31.6), p < 0.05), and sublingual nitrate consumption significantly reduced (placebo 11.8 (15.2) vs. zibotentan 8.8 (12.9), p < 0.05. Zibotentan improved the frequency of spontaneous angina episodes and reduced sublingual nitrate consumption in patients unresponsive to standard anti-anginal therapy.

Clinical features of coronary artery disease and 5-year survival of patients after myocardial infarction against the background of depressive disorders

Aim. To assess the features of the clinical picture of coronary artery disease (CAD) and the prognosis of patients with myocardial infarction with depressive disorder (DD).&#x0D; Materials and methods. We examined 101 patients with stable CAD who had myocardial infarction more than six months ago: 67 CAD patients with depression (Group 1) and 34 CAD patients without depression (Group 2). The clinical picture of CAD was assessed by complaints, angina self-monitoring diaries, and exercise tests. The presence and severity of DD was determined using psychometric scales: BDI (Beck Depression Scale), HADS (Hospital Anxiety and Depression Scale) and the opinion of a psychiatrist. Five-year survival information was obtained through telephone interviews with patients and their relatives.&#x0D; Results. In patients with CAD and DD in comparison with patients without DD self-monitoring diaries revealed more frequent angina attacks: 9 [6; 12] vs 6 [4; 7] per week (p=0.0001), the greater need for sublingual nitrates: 2 [0; 9] pills vs 0 [0; 4] pills (p=0.0001). DD significantly reduced exercise tolerance: 370 [250; 450] meters vs 435 [350; 500] meters using the six-minute walk test (p=0.04), according to the results of bicycle ergometry – 50 [25; 75] W vs 75 [50; 75] W (p=0.03). After 5 years of follow-up patients with comorbidities (CAD and DD) had a greater number of deaths: 13 (19.4%) vs 2 (5.9%), respectively, survived – 54 (80.6%) vs 32 (94.1%) (Gehan–Wilcoxon test, p=0.04).&#x0D; Conclusion. The comorbidity CAD and DD leads to a worsening of the clinical course of CAD and prognosis, which actualizes the need for verification of the diagnosis of DD and timely prescription of antidepressant therapy.

Safety of prehospital intravenous bolus dose nitroglycerin in patients with acute pulmonary edema: A 4-year review.

Intravenous nitrates are a primary therapy for hypertensive congestive heart failure (CHF) with acute pulmonary edema (APE) in the hospital setting. Historically, sublingual nitrates are the mainstay of emergency medical services (EMS) pharmacologic therapy for these patients. We aimed to evaluate the safety of prehospital bolus dose intravenous nitroglycerin in patients with APE. This is a retrospective evaluation of EMS data between March 15, 2018, and March 15, 2022, where CHF with APE was suspected and bolus-dose intravenous nitroglycerin was administered. Protocol inclusion criteria were hypertension (systolic blood pressure [SBP]>160mmHg) and acute respiratory distress, with a presumption of decompensated CHF with APE. These patients received 1mg intravenous nitroglycerin, with the option to repeat once for ongoing distress if the SBP remained>160mmHg. The primary outcomes were adverse events, defined as hypotension (SBP<90mmHg), syncope, vomiting, or dysrhythmia. The final analysis included 235 patients. In patients receiving intravenous bolus nitroglycerin, the median (interquartile range [IQR]) initial and final EMS SBP values decreased from 198mmHg (180-218) to 168 (148-187), respectively. The median (IQR) pulse decreased from 108 (92-125) to 103 (86-119), and the median oxygen saturation increased from 89% (82-95) to 98% (96-99). Three episodes (1.3%) of asymptomatic hypotension occurred, and none required intervention. This study supports a favorable safety profile for prehospital bolus-dose intravenous nitroglycerin for decompensated CHF with APE. Blood pressure, heart rate, and oxygen saturation improvements are also demonstrated. Further, prospective studies are needed to confirm these findings.

Pharmacological and non-pharmacological prophylaxis in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a narrative review

Endoscopic retrograde cholangiopancreatography is a diagnostic and therapeutic procedure for various gastrointestinal problems. Pancreatitis is a severe complication of the procedure. The main objective of this study was to address if post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be prevented and what are the various pharmacological and non-pharmacological options along with their efficacy. Keywords “post-ERCP” and “pancreatitis” were used to search articles in Pubmed. Randomized controlled trials on patients undergoing ERCP due to any disease using pharmacological or non-pharmacological intervention published in the last 7 years were included. Observational studies, descriptive studies, reviews, and studies with no full access were excluded. The primary outcome in the trials was a frequency of post-ERCP pancreatitis. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most effective drugs in reducing the incidence of pancreatitis. The preferred route was rectal. After NSAIDs, intravenous hydration and sublingual nitrate showed promising outcomes, especially when combined with rectal NSAIDs. Other drugs like magnesium sulfate and nafamostat mesilate did reduce the incidence, but the results were not statistically significant. Epinephrine spray on duodenal papilla showed no benefits and instead had a risk of increasing the incidence. Stent placement also reduced the incidence of pancreatitis. In conclusion, rectal NSAIDs alone or combined with IV hydration and sublingual nitrate significantly reduced the incidence of pancreatitis, and stent placement was comparable to pharmacological interventions. Thus, regular use of pharmacological interventions before the procedure can help to reduce the incidence of this grave complication.

Can Sublingual Nitrate Improve Visualization of Lower Limb Arteries on Computed Tomography Angiography?

The aim of the study is to evaluate the role of sublingual nitrate in improving vessel visualization on peripheral computed tomography angiography (CTA). Fifty patients clinically diagnosed with peripheral arterial disease of the lower limb were prospectively included in this study: Twenty-five underwent CTA after sublingual nitrate administration (nitrate group) and 25 without (non-nitrate group). Two blinded observers qualitatively and quantitatively assessed the data thus generated. The mean luminal diameter, intraluminal attenuation, site, and percentage of stenosis were evaluated in all segments. Assessment of collateral visualization at sites of significant stenosis was also done. Patients in the nitrate and non-nitrate groups were similar in age and sex characteristics (P > 0.05).On subjective evaluation, there was significantly improved visualization of the femoropopliteal and tibioperoneal vasculature of the lower limb in the nitrate group compared with the non-nitrate group (P < 0.05). Quantitative evaluation showed a statistically significant difference in the measured arterial diameters for all evaluated segments in the nitrate group versus the non-nitrate group (P < 0.05). Intra-arterial attenuation was significantly greater for all segments in the nitrate group resulting in better contrast opacification in these studies. Collateral visualization around segments with more than 50% stenosis/occlusion was also better in the nitrate group. Our study suggests that nitrate administration before peripheral vascular CTA can improve visualization, especially in the distal segments by increasing the vessel diameter and intraluminal attenuation along with better delineation of the collateral circulation around stenotic areas. It may also improve the number of evaluable segments of vasculature in these angiographic studies.

279 LAYERED PLAQUES: NOT ALL ARE HEALED

Abstract Layered plaques are the effect of a previous plaque event. They are associated with coronary spasm and found in more than 50% of patients with stable angina and a quarter of those with an acute coronary syndrome. Nevertheless, it is not clear whether their presence is indicative of a healing process or rather is predictive of an increased risk of future events. A 71-year-old male, heavy smoker and hypertensive, presented with episodes of angina at rest that resolved spontaneously in less than 5 minutes, with evidence of ST-segment elevation (STE) in the lower leads during one of these episodes. Coronary angiography showed an intermediate stenosis at the end of the mid segment of the dominant right coronary artery (RCA) (Figure A). Optical coherence tomography (OCT) revealed a layered plaque, consisting of high backscattering layers alternated with low reflection layers (Figures A1-3). Given the minimum luminal area of 3.65 mm2 and the absence of other criteria for plaque instability (erosion, thin-cap, etc.), we treated the patient conservatively with medical therapy alone, consisting of a single antiplatelet agent and a high-dose statin with ezetimibe. A non-dihydropyridine calcium antagonist and a long-acting nitrate were started given the suspicion of coronary spasm. Four months later the patient returned to the emergency department for persistent oppressive chest pain unresponsive to sublingual nitrates with evidence of STE in the lower leads. Emergency coronary angiography showed an acute occlusion of RCA with TIMI 0 flow in correspondence to the layered plaque highlighted 4 months earlier on OCT (Figure B). Antegrade flow was restored with manual thrombus aspiration (Figure C) and OCT showed lesion progression with many new layers, together with a cavity suggestive of plaque rupture (Figures C1-3). A 3.5×38 mm everolimus eluting stent was deployed – based on OCT sizing – and post-dilated with a 4.0×8 mm non-compliant balloon, obtaining an excellent angiographic result with TIMI 3 flow (Figure D). Low-reflecting layers within layered plaques are generally considered to be lipid deposits, but they could also represent intraplaque haemorrhages, generated by coronary spasm. The haematoma can be reorganised within the plaque to create a new layer, leading to lesion progression without necessarily requiring a loss of endothelial integrity. The progressive increase of the haematoma may lead to plaque rupture when the pressure exceeds the resistance of superficial layers. This case reveals a new possible mechanism of plaque progression in patients with coronary spasm and explains how layered plaques can be ambivalently considered to be either stable or vulnerable. Their treatment should be meticulously tailored not only based on classical criteria of plaque instability but also according to the underlying trigger mechanism.

Sublingual Nitrates for Patients as a Default in the Post-ACS Discharge Pack: Is It Time for a Rethink?

HomeCirculationVol. 145, No. 11Sublingual Nitrates for Patients as a Default in the Post-ACS Discharge Pack: Is It Time for a Rethink? No AccessArticle CommentaryRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessArticle CommentaryRequest AccessFull TextSublingual Nitrates for Patients as a Default in the Post-ACS Discharge Pack: Is It Time for a Rethink? Avedis A. Ekmejian, MBBS, MSc, Ravinay Bhindi, MBBS, MSc, PhD and Gemma A. Figtree, MBBS, DPhil Avedis A. EkmejianAvedis A. Ekmejian Department of Cardiology, Royal North Shore Hospital, Sydney, Australia (A.A.E., R.B., G.A.F.). Search for more papers by this author , Ravinay BhindiRavinay Bhindi Department of Cardiology, Royal North Shore Hospital, Sydney, Australia (A.A.E., R.B., G.A.F.). Cardiovascular Discovery Group, Kolling Institute of Medical Research (R.B., G.A.F.), University of Sydney, Australia. Search for more papers by this author and Gemma A. FigtreeGemma A. Figtree Correspondence to: Gemma A. Figtree, MBBS, DPhil, Royal North Shore Hospital, Cardiovascular Discovery Group, Kolling Institute, University of Sydney, Level 12, Kolling Institute of Medical Research, 10 Westbourne Street, St Leonards, 2065, Australia. Email E-mail Address: [email protected] Department of Cardiology, Royal North Shore Hospital, Sydney, Australia (A.A.E., R.B., G.A.F.). Cardiovascular Discovery Group, Kolling Institute of Medical Research (R.B., G.A.F.), University of Sydney, Australia. Charles Perkins Centre (G.A.F.), University of Sydney, Australia. Search for more papers by this author Originally published14 Mar 2022https://doi.org/10.1161/CIRCULATIONAHA.121.058008Circulation. 2022;145:791–792"Sublingual Nitrates for Patients as a Default in the Post-ACS Discharge Pack: Is It Time for a Rethink?." Circulation, 145(11), pp. 791–792FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 792.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Gemma A. Figtree, MBBS, DPhil, Royal North Shore Hospital, Cardiovascular Discovery Group, Kolling Institute, University of Sydney, Level 12, Kolling Institute of Medical Research, 10 Westbourne Street, St Leonards, 2065, Australia. Email gemma.[email protected]edu.au

Abstract 14075: Infective Endocarditis Associated With Irreversible Coronary Spasm and Cardiac Arrest

Introduction: Coronary artery spasm (CAS) can elicit ischemia with transient ST-segment deviation that usually responds to nitrates; however, CAS can precipitate arrhythmias leading to sudden cardiac arrest. Infective endocarditis (IE) is associated with the acute coronary syndrome (ACS) usually via coronary embolism and compression secondary to peri-annular complications. CAS in association with IE causing ACS is extremely rare. Case: A 54-year-old man had a recent ST-elevation (STE) myocardial infarction, which required stenting to obtuse marginal artery (OM2) artery. He presented with a fever for one week. A new diastolic murmur at the aortic area on examination. Echocardiography showed a bicuspid aortic valve with perforation and new-onset aortic regurgitation suggestive of vegetation. Diagnosis of infective endocarditis was established, and the patient was started on medical treatment and was being prepared for surgical repair. During the hospital stay, he had recurrent episodes of severe chest pain accompanied by transient STE on ECG but normal troponin level. It was always responding to sublingual nitrates. CT coronary Angiogram showed no significant coronary stenosis and patent stent in OM2. The patient had again an attack of severe chest pain with ECG showed extensive STE then he developed pulseless electrical activity. Result: Resuscitation was started and emergency coronary angiography was performed and showed severe spasms in both LAD and LCX with TIMI-1 flow. A repeated image during resuscitation showed patent arteries with TIMI-III flow. A prolonged CPR in Cath-lab failed and the patient died. Although there was no clear explanation of the mechanism, the simultaneous association between the CAS and IE raises the suspicion of a possible relationship between both pathologies. Conclusions: Severe coronary spasm should be considered as a possible cause of ACS in association with IE.

Nitric oxide for the prevention and treatment ofviral, bacterial,protozoalandfungalinfections.

Although the antimicrobial potential of nitric oxide(NO)is widelypublished, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses.Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite andS-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (includingβ-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts in vitro. Therapeutic effects have been seen in animal models in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trialsshould test dietary inorganic nitrate forpre- or post-exposureprophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment ofmild-to-severe infections, including due to SARS-CoV-2(COVID-19). This review summarises the evidence base from in vitro, in vivoand early phase clinical studies of NO activity inviral, bacterial,protozoalandfungalinfections.

The Efficacy of Ringer lactate and Sublingual Nitrates vs Indomethacin to Reduce Post-ERCP Pancreatitis: A Review Article

The Efficacy of Ringer lactate and Sublingual Nitrates vs Indomethacin to Reduce Post-ERCP Pancreatitis: A Review Article

A Cost-Effectiveness Analysis for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis in the United States

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common adverse event after endoscopic retrograde cholangiopancreatography, and is responsible for substantial morbidity and health care expenditures of at least $200 million. Therapies for PEP prevention include pancreatic stent placement (PSP), rectal indomethacin, sublingual nitrates, and aggressive lactated Ringer's hydration. Our objective was to determine which PEP prophylactic strategies are cost effective. We developed 2 separate decision trees to evaluate PEP prophylactic strategies. The first, in high-risk patients, compared rectal indomethacin, PSP, PSP with indomethacin, sublingual nitrates, aggressive hydration with lactated Ringer's, and no prophylaxis. The second, in average-risk patients, compared rectal indomethacin, sublingual nitrates, aggressive hydration, and no prophylaxis. We used incidence rates, transition probabilities, and costs from publications and public data sources. Outcome measures were reported as incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life years (QALYs). Compared with no prophylaxis, all strategies were cost effective at a WTP of $100,000 in preventing PEP in high-risk patients. When directly compared with each other, rectal indomethacin was the cost-effective strategy in high-risk patients ($31,589/QALYs). In average-risk patients, indomethacin and sublingual nitrates were cost effective at a WTP of $100,000/QALYs compared with no prophylaxis. When directly compared with each other, rectal indomethacin was the cost-effective strategy ($53,016/QALYs). Rectal indomethacin was the cost-effective strategy for preventing PEP in both average-risk and high-risk patients undergoing endoscopic retrograde cholangiopancreatography. All strategies were cost effective when compared with no prophylaxis in high-risk patients, whereas all strategies except for aggressive hydration with lactated Ringer's were cost effective in average-risk patients. Further studies are needed to improve the utilization of PEP prevention strategies.

English

Angioplasty is considered superior to fibrinolytic therapy in acute myocardial infarction (AMI) if the patient receives it within the therapeutic window. It is unclear if such advantages are available for patients who need to travel from a community hospital to a facility where invasive care is available, since primary thrombolysis often re-establishes coronary artery blood flow in patients with ST elevation acute myocardial infarction (STEMI). At the most severe end of the range of acute coronary syndromes is ST - segment elevation myocardial infarction (STEMI), which generally occurs when a fibrin-rich thrombus fully occludes an epicardial coronary artery. The diagnosis of STEMI is based on clinical features and persistent ST-segment elevation as evidenced by 12 - lead electrocardiography. Patients with STEMI should have a quick reperfusion treatment evaluation and a reperfusion strategy should be performed immediately following contact with the system. All patients with AMI who had chest pain within 12 hours were evaluated. The detailed history of chest pain, character, and radiation, had been taken in terms of duration from the beginning of chest pain in minutes. After 10 minutes, patients were given 10 mg of sublingual isosorbide dinitrate and repeated ECG. Patients were excluded if chest pain or ST elevation was resolved after 10 minutes of nitrate administration. In the analysis only those cases in which chest pain and ST shift were not resolved following sublingual nitrates. Serum CKMB estimates have been performed. All patients were treated with 1.5 million IU streptokinase in 100 ml of normal saline for more than 45 minutes. Clinical assessment for 2 hours every half hour was done to evaluate: 1. Chest pain reduction in a subjective scale percentage and to assess changes in the Killip class. 2. Continuous ECG monitoring of reperfusion rhythm occurrences. Patients are assessed at the end of 2 hours of follow-up for: a. Percentage reduction in subjective chest pain a. A 12 lead ECG to identify changes in the ST height c. Repeat CK-MB estimate. Patients with thrombolysis were classified into two classes on the basis of presence or absence of SCR at the end of two hours of initiation. Those with successful reperfusion were grouped into the SCR Group and into the SCR (negative) Group without successful reperfusion. Coronary prognostic index is a set of questionnaires which prognosticate the outcome in AMI. This review describes the role of Coronary Prognostic Index and thrombolysis in patients of STEMI. KEY WORDS ECG, AMI, STEMI, Angioplasty

Nitric oxide for the prevention and treatment ofviral, bacterial,protozoalandfungalinfections.

Although the antimicrobial potential of nitric oxide(NO)is widelypublished, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses.Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite andS-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (includingβ-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts in vitro. Therapeutic effects have been seen in animal models in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trialsshould test dietary inorganic nitrate forpre- or post-exposureprophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment ofmild-to-severe infections, including due to SARS-CoV-2(COVID-19). This review summarises the evidence base from in vitro, in vivoand early phase clinical studies of NO activity inviral, bacterial,protozoalandfungalinfections.

Efficacy of Combining Aggressive Hydration With Rectal Indomethacin in Preventing Post-ERCP Pancreatitis: A Systematic Review and Network Meta-Analysis.

Postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography pancreatitis (ERCP). No randomized controlled trial (RCT) has compared the efficacy of the American Society of Gastrointestinal Endoscopy and European Society of Gastrointestinal Endoscopy recommended interventions for PEP prevention. We assessed the effectiveness of these interventions using network meta-analysis. PubMed, EMBASE, and Cochrane databases were searched to identify RCTs investigating guideline-recommended interventions and their combinations [rectal nonsteroidal anti-inflammatory drugs (NSAIDs): indomethacin or diclofenac, pancreatic stent (PS), aggressive hydration (AH), sublingual nitrate) for PEP prevention. We performed direct and Bayesian network meta-analysis, and the surface under the cumulative ranking curve to rank interventions. Subgroup network meta-analysis for high-risk populations was also performed. We identified a total of 38 RCTs with 10 different interventions. Each intervention was protective against PEP on direct and network meta-analysis compared with controls. Except AH+diclofenac and NSAIDs+ sublingual nitrate, AH+indomethacin was associated with a significant reduction in risk of PEP compared with PS [odds ratio (OR), 0.09; credible interval (CrI), 0.003-0.71], indomethcin+PS (OR, 0.09; CrI, 0.003-0.85), diclofenac (OR, 0.09; CrI, 0.003-0.65), AH (OR, 0.09; CrI, 0.003-0.65), sublingual nitrate (OR, 0.07; CrI, 0.002-0.63), and indomethacin (OR, 0.06; CrI, 0.002-0.43). AH with either rectal NSAIDs or sublingual nitrate had similar efficacy. AH+indomethacin was the best intervention for preventing PEP with 95.3% probability of being ranked first. For high-risk patients, although the efficacy of PS and indomethacin were comparable, PS had an 80.8% probability of being ranked first. AH+indomethacin seems the best intervention for preventing PEP. For high-risk patients, PS seems the most effective strategy. The potential of combination of interventions need to be explored further.

Assessment of Endothelial Dysfunction by Brachial Artery Flow-Mediated Dilatation in Postmenopausal Women at Low Risk for Cardiovascular Disease.

Objective:The objective is to compare endothelial dysfunction measured by brachial artery flow-mediated dilation (BAFMD) in nonobese, nondiabetic post-menopausal women with their age-matched menstruating controls and to identify the correlation of BAFMD with Framingham risk score (FRS) and with the individual parameters of FRS in low-risk women.Methods:This study was done in the department of Obstetrics and Gynaecology, Chandigarh, India, for 1 year. Fifty postmenopausal and 50 menstruating females aged 45–55 years who were nondiabetic and nonobese and were low risk according to FRS were selected as cases and controls, respectively. All cases and controls were age-matched. The diameter of the brachial artery and the blood flow in it was measured at rest. Ischemia was produced and released after 5 min. The maximum blood flow velocity diameter of the brachial artery was measured. After 10 min of reactive hyperemia, 400 μg of sublingual nitrate was given, and vasodilatation mediated by nitroglycerine was subsequently measured.Results:Menopause did not have any significant effect on the endothelial dysfunction as measured by the brachial artery flow-mediated dilatation (P = 0.74) but did influence vascular smooth muscle as measured by nitroglycerine-mediated dilatation (P = 0.028). A significant correlation was found between flow-mediated dilatation with FRS helps us conclude that flow-mediated dilation is a reliable tool to estimate the cardiovascular risk (P < 0.001). A strong correlation was found between nitroglycerine-mediated dilatation and flow-mediated dilatation, demonstrating that both endothelial dysfunction and vascular smooth muscle are interrelated (P < 0.001).Conclusion:Menopause did not affect endothelial function, but it has a significant effect on vascular smooth muscle function. To know the effect of longer duration of menopause on vascular function in elderly women further studies with large number of postmenopausal women of different duration of menopause, may be needed.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non-steroidal anti-inflammatory drugs: A systematic review and network meta-analysis.

Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta-analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP. We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents. The NMA included 24 studies evaluating 14 regimens in 11321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin+lactated Ringer's solution, followed by diclofenac+nitrate and indomethacin+normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high-risk group. Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.

Emerging Therapies to Prevent Post-ERCP Pancreatitis

The aim of this review is to evaluate emerging, novel therapies for the prevention of post-ERCP pancreatitis. Rectal indomethacin reduces the risk of pancreatitis in low- and average-risk patients, who comprise the majority of patients undergoing ERCP. An 8-h protocol of aggressive lactated Ringer's reduces the risk of pancreatitis in average-risk patients. Sublingual nitrate may provide additional benefit to rectal NSAIDs in preventing PEP. A tacrolimus trough > 2.5ng/mL was recently shown to be associated with a lower risk of PEP in liver transplant patients undergoing ERCP. Routine usage of rectal indomethacin in all patients undergoing ERCP reduces the risk of PEP. Pancreatic-duct stents reduce the risk of PEP in high-risk patients. There is emerging data that aggressive hydration with lactated Ringer's and nitrates may further reduce PEP. Tacrolimus is a promising potential agent to prevent PEP but needs further clinical study.

S0006 Efficacy of Combining Aggressive Hydration With Rectal Indomethacin in Preventing Post-ERCP Pancreatitis: A Systemic Review and Network Meta-Analysis

INTRODUCTION: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is a major adverse event after endoscopic retrograde cholangiopancreatography. No RCT has compared the efficacy of all American Society of Gastrointestinal Endoscopy (ASGE)- and European Society of Gastrointestinal Endoscopy (ESGE)-recommended interventions for PEP prevention. We assessed the effectiveness of these interventions and their combinations amongst each other using network meta-analysis approach. METHODS: We conducted a literature search of PubMed, EMBASE, and Cochrane databases from inception to January 14, 2020, to identify RCTs comparing ASGE-and ESGE-recommended interventions -including rectal NSAIDs, pancreatic stent (PS), aggressive hydration (AH), sublingual nitrate or combinations of those - with each other or with the control group for PEP prevention (primary outcome). RCTs defining PEP only as per cotton's criteria or consensus criteria were included. Odds ratios (ORs) with 95% credible intervals (CrIs) were reported for network comparisons. We also did a subgroup network meta-analysis for high-risk patients. We used the surface under the cumulative ranking curve to rank interventions in terms of PEP prevention. Model consistency was assessed with the node splitting method. RESULTS: We identified a total of 38 RCTs with ten different interventions (Figure 1Figure 1.: Network Plots Showing Direct Comparisons Available Among Interventions. A) All interventions. B) Interventions for high-risk patients. The thickness of the line connecting two interventions are proportional to available RCTs comparing them.). Each intervention was protective against PEP on network meta-analysis compared to controls as shown in Figure 2Figure 2.: League table showing results of all possible comparison of all interventions. Odds ratio with 95% CrI in a particular cell represents a comparison of column defining treatment to raw defining treatment. All statistically significant comparisons are highlighted in green colour. AH: Aggressive hydration; I: Indomethacin; D: Diclofenac; N: Nitrate; S: Stent. “+” represents a combination of intervention.. Except AH+diclofenac and NSAIDs + sublingual nitrate, AH+indomethacin was associated with a significant reduction in risk of PEP compared to PS (OR: 0.09; CrI: 0.003–0.71), indomethcin+PS (OR: 0.09; CrI: 0.003–0.85), diclofenac (OR: 0.09; CrI: 0.003–0.65), AH (OR: 0.09; CrI: 0.003–0.65), sublingual nitrate (OR: 0.07; CrI: 0.002–0.63), and indomethacin (OR: 0.06; 0.002–0.43). AH with either rectal NSAIDs or sublingual nitrate had similar efficacy as shown in Figure 2. AH+indomethacin was the best intervention for preventing PEP with 95.3% probability of being ranked first (Figure 3AFigure 3.: SUCRA Based on Cumulative Probabilities. A) All interventions. B) Interventions for high-risk patients. AH indicates aggressive hydration; D, rectal diclofenac; I, rectal indomethacin; N, sublingual nitrate; S, pancreatic stent; SUCRA, surface under the cumulative.). For high-risk patients, although the efficacy of PS and indomethacin were comparable, PS had an 80.8% probability of being ranked first (Figure 3B). Node splitting with P-value < 0.05 for direct and indirect comparison confirmed model consistency. CONCLUSION: Combination of rectal indomethacin with aggressive hydration seems the best intervention for preventing PEP. For high-risk patients, pancreatic stent seems the most effective strategy.