Nitroglycerin Group Research Articles

Mesenteric blood flow and muscle sympathetic nerve activity during vasovagal syncope.

Vasovagal syncope is thought to be mediated by a progressive fall in cardiac output secondary to venous pooling of blood in the splanchnic circulation. How and when this occurs before syncope has not been determined. A total of 20 patients who became hypotensive during head-up tilt (age 40.9 ± 3.4 years; 10 females) were divided into two groups-the glyceryl trinitrate (GTN) group (n = 12) and the vasovagal syncope (VVS) group (n = 8) - on the basis of whether or not nitroglycerine provocation was required. They were compared with a control group (age 38.6 ± 3.3; 8 females; n = 13). Hemodynamics, including superior mesenteric artery blood flow (SMABF) and muscle sympathetic nerve activity (MSNA) were recorded continuously during early tilt, presyncope and recovery. We used pixel-weighting to calculate average velocity from the pulsed Doppler velocity envelope. During baseline and early tilt, resistance to mesenteric blood flow was lower in the VVS group: 0.30 ± 0.02 to 0.30 ± 0.02mmHg/ml/min versus controls 0.30 ± 0.03 to 0.38 ± 0.04mmHg/ml/min (p = 0.05). During presyncope, as blood pressure and stroke volume gradually fell, SMABF was higher in the VVS group, falling from 370 ± 46 to 248 ± 35ml/min, versus controls, falling from 342 ± 51 to 233 ± 19 (p = 0.03). At this time, MSNA was lower in the VVS group than controls: 39 ± 4 to 34 ± 3 bursts/min versus 45 ± 2 to 48 ± 3 (p = 0.001). During presyncope, increased splanchnic blood flow may pool more blood in capacitance vessels resulting in decreased venous return and cardiac output. This may be secondary to decreased vasoconstrictor sympathetic activity.

Nitroglycerin versus milrinone for low central venous pressure in patients undergoing laparoscopic hepatectomy: a double-blinded randomized controlled trial

BackgroundConventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients’ recovery.MethodsIn total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2–0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2–0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome.ResultsBlood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P < 0.05). Both the nitroglycerin group and milrinone group exerted similar CVP (P > 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P < 0.05) and also exhibited higher cardiac index and cardiac output during the surgery (P < 0.05). Significant differences were also found in terms of fluids administered during hepatectomy, urine volume during hepatectomy, total urine volume, and norepinephrine dosage used in the surgery between the two groups. The two groups showed a similar incidence of postoperative complications (P > 0.05).ConclusionOur findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin.Trial registrationChiCTR2200056891,first registered on 22/02/2022.

Use of Dexmedetomidine versus Nitroglycerine to Provide Hypotensive Anesthesia in ENT Surgeries (Functional Endoscopic Sinus Surgery)

Abstract Background controlled (deliberate/induced) hypotension is a technique by which the arterial blood pressure is lowered in a controllable manner to reduce surgical blood loss and improve the operative field visibility. There are pharmacological and nonpharmacological techniques for inducing hypotension. The nonpharmacological methods for deliberate hypotension include positioning and positive pressure ventilation to control venous return. Aim of the Work to evaluate the efficacy of dexmedetomidine (DEX) as a hypotensive agent in comparison to nitroglycerin (NTG) in FESS regarding the bloodless field, reduction of mean arterial blood pressure, decrease inhalational anesthetic requirements (MAC), decrease perioperative opioid requirements, increase the time to first postoperative analgesic request and recovery profile and increase hemodynamics stability. Patients and Methods we conducted this study on 20 patients who were planned to perform functional endoscopic sinus surgery and were randomly distributed into 2 equal groups: 10 patients received dexamedotomidine and equal number of patients received nitroglycerine. Serial measurements of mean arterial blood pressure and heart rate were obtained and records between both groups were compared. Results There were statistically significant differences between both groups regarding heart rate as mean values of heart rate were lower among dexamedotomidine group. There were no statistically significant differences between both groups regarding mean arterial blood pressure values at different time points during the operation. Regarding the period after stopping infusion, mean values of heart rate and blood pressure were lower among dexamedotomidine group than nitroglycerine group after 5 minutes and after 10 minutes and the differences had statistically significant differences. Regarding postoperative period, both groups were comparable regarding heart rate and blood pressure immediately postoperative. Conclusion From the results of this study, we could conclude that both Dexmedetomidine and Nitroglycerin can be effectively used in induced hypotensive anesthesia for ENT surgery as FESS. Both groups were comparable with intra operative MAP with no statistically significant differences. This study also show that Dexmedetomidine has added advantages as better haemodynamic stability than Nitroglycerin (No rebound HTN, no tachycardia). Has sedative and analgesic effect, reduce requirement of anesthetic agents and perioperative analgesia. Postoperative recovery score (Time to reach modified Aldert score more than nine significantly higher. Postoperative complication as nausea and vomiting is less.

Genistein mitigates nitroglycerine-induced migraine: modulation of nitric oxide-mediated vasodilation and oxidative stress.

Migraine is a widespread brain condition described by frequent, recurrent episodes of incapacitating, moderate-to-severe headaches with throbbing pain that are usually one-sided. It is the 2nd most debilitating state lived with disability in terms of years, with a prevalence rate of 15-20%. Significant drops in estrogen levels have been associated with triggering acute migraine attacks in certain cases. Phytoestrogens are plant-derived compounds that resemble estrogen in structure, enabling them to imitate estrogen's functions in the body by attaching to estrogen receptors. Thus, the study was aimed to explore the protective effect of genistein against migraine. Moreover, the role of nitric oxide was also studied in the observed effect of genistein. Nitric oxide (NO) is implicated in migraine pathophysiology due to its role in promoting cerebral vasodilation and modulation of pain perception. Exploring L-NAME, a nitric oxide synthase inhibitor in migraine research helps scientists better understand the role of NO in migraine. Nitroglycerine treatment significantly increased the facial-unilateral head pain and spontaneous pain, as evidenced by the increased number of head scratching and groomings. Nitroglycerine treatment also induced anxiogenic behavior in mice. A significant reduction in the number of entries in the light phase and open arm, respectively. Biochemical analysis indicated a significant increase in inflammatory and oxidative stress in the nitroglycerin group. A significant increase and decrease in brain TBARS and GSH were observed with nitroglycerine treatment, respectively. Moreover, nitroglycerine treatment has uplifted the serum TNF-α level. Genistein (20mg/kg) significantly mitigated the facial-unilateral head pain, spontaneous pain, photophobia, and anxiety-like behavior induced by nitroglycerine. Biochemical analysis showed that genistein (20mg/kg) significantly abrogated the nitroglycerine-induced lipid peroxidation and increased serum TNF-α level. Genistein treatment also upregulated the brain GSH level and downregulated the serum TNF-α level. The L-NAME-mediated alleviation of the protective effect of genistein might be attributed to the vasodilatory effect of L-NAME. Conclusively, it can be suggested that genistein might provide relief from migraine pain by inhibiting nitric oxide-mediated vasodilation and oxidative stress.

Comparison of the efficacy of nifedipine with ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor: a systematic review and meta-analysis

BackgroundSome studies have compared the efficacy of nifedipine with that of other tocolytic drugs in the treatment of preterm labor, but the reported results are conflicting.ObjectiveTo compare the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor.MethodsIn this systematic review and meta-analysis, PubMed/MEDLINE, Scopus, Clarivate Analytics Web of Science, and Google Scholar were searched until April 3,2024 using predefined keywords. Randomized controlled trials (RCTs) and clinical trials that compared the efficacy of nifedipine with that of ritodrine, nitroglycerine and magnesium sulfate for the management of preterm labor were included. Two authors independently reviewed the articles, assessed their quality and extracted the data. The quality of the included RCTs based on the Cochrane Risk of Bias Tool 1 for clinical trial studies. The risk difference (RD) with the associated 95% confidence interval (CI) was calculated. A forest plot diagram was used to show the comparative point estimates of nifedipine and other tocolytic drugs on the prevention of preterm labor and their associated 95% confidence intervals based on the duration of pregnancy prolongation. Study heterogeneity was evaluated by the I2 index, and publication bias was evaluated by Egger’s test.ResultsForty studies enrolling 4336 women were included. According to our meta-analysis, there was a significant difference in the prolongation of preterm labor within the first 48 h between the nifedipine group and the nitroglycerine group (RD, -0.04; 95% CI, -0.08 to -0.00; I2: 32.3%). Additionally, there were significant differences between nifedipine and ritodrine (RD, 0.11; 95% CI, 0.02 to 0.21; I2, 51.2%) for more than one week RD, 0.10; 95% CI, 0.03 to 0.19; I2, 33.2%) and for 34 weeks and more. The difference between nifedipine and magnesium sulfate was not significant in any of the four time points.ConclusionsConsidering the superiority of nifedipine over ritodrine and nitroglycerine and its similar efficacy to magnesium sulfate for tocolysis, it seems that the side effects of these options determine the first drug line.

Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID): A potential neuroprotection strategy for acute ischemic stroke (AIS) patients

Despite advances in intravenous thrombolysis and endovascular thrombectomy, numerous acute ischemic stroke survivors continue to experience various disability levels. The nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), has been identified as a potential neuroprotective agent against ischemic damage. We evaluated the safety and feasibility of intravenous GTN in AIS patients. Subsequently, we conducted a secondary analysis to assess for possible efficacy of GTN as a neuroprotectant. We conducted a prospective, double-blind, randomized controlled trial in the Stroke Intervention & Translational Center (SITC) in Beijing Luhe Hospital, Capital Medical University (ChiCTR2100046271). AIS patients within 24 h of stroke onset were evenly divided into GTN or control groups (n = 20 each). The GTN group received intravenous GTN (5 mg in 50 ml saline at a rate of 0.4 mg/h for 12.5 h/day over 2 days), while controls were administered an equivalent volume of 0.9% saline. Both groups followed standard Stroke Guidelines for treatment. Safety measures focused on SBP<110 mmHg and headache occurrence. Efficacy was assessed via the 90-day modified rankin score (mRS) and the national institutes of health stroke score (NIHSS). Of the 40 AIS patients, baseline characteristics such as age, gender, risk factors, and pre-mRS scores showed no significant difference between the groups. Safety measures of SBP<110 mmHg and headache occurrence were comparable. Overall, 90-day mRS (1 vs. 1) and NIHSS (1 vs. 1) did not significantly differ between groups. However, the GTN-treated group had a benefit in enhancing NIHSS recovery (△NIHSS 4.5 vs. 3, p = 0.028), indicating that GTN may augment recovery. Subgroup analyses revealed a benefit in the GTN group at the 90-day NIHSS score and △NIHSS follow up for non-thrombolysis patients (1 vs. 2, p = 0.016; 5 vs. 2, p = 0.001). Moreover, the GTN group may benefit mild stroke patients in NIHSS score at 90 day and △NIHSS observed at 90 days (1 vs. 1, p = 0.025; 3 vs. 2 p = 0.002). Overall, while preliminary data suggest GTN might aid recovery in NIHSS improvement, the evidence is tempered due to sample size limitations. The RIGID study confirms the safety and feasibility of intravenous GTN administration for AIS patients. Preliminary data also suggest that the GTN group may provide improvement in NIHSS recovery compared to the control group. Furthermore, a potential benefit for non-thrombolysis patients and those with mild stroke symptoms was identified, suggesting a possible potential role as a tailored intervention in specific AIS subgroups. Due to the limited sample size, further larger RCT will be necessary to replicate these results. Trial Registrationwww.chictr.org.cn, identifier: ChiCTR2100046271.

Gadolinium-based contrast agents aggravate mechanical and thermal hyperalgesia in a nitroglycerine-induced migraine model in male mice

In the diagnosis of migraine, which is a neurovascular disease, gadolinium-based contrast agents (GBCAs) are used to rule out more serious conditions. On the other hand, it remains unclear as a scientific gap whether GBCAs may trigger migraine-related pain. The aim of this study was to investigate the effect of GBCAs on mechanical and thermal pain behaviour in a nitroglycerin (NTG)-induced migraine model in mice.NTG (10 mg/kg) was administered intraperitoneally to adult (6–8weeks old) BALB/c mice 2 h before behavioral tests 5 times every other day on days 1st, 3rd, 5th and 9th to induce migraine model (N = 50). As GBCAs, gadobenate dimeglumine (linear-ionic), Gadodiamide (linear-nonionic), and gadobutrol (macrocyclic-nonionic) were delivered intravenously through the tail vein of mice for 5 days on test days. Mechanical pain threshold (plantar and facial withdrawal threshold) was evaluated by plantar von Frey and periorbital von Frey tests on days 1st, 5th, and 9th, and thermal pain threshold (latency) was evaluated by hot plate and cold plate tests on days 3rd and 7th. There was a statistically significant increase in mechanical and thermal hyperalgesia in NTG administered groups compared to the control group. Gadodiamide, gadobutrol and gadobenate dimeglumine administration significantly decreased latency, paw and facial withdrawal threshold (0.18 ± 0.05, 0.17 ± 0.07, 0.16 ± 0.09; 9th day values respectively) compared to NTG group (0.27 ± 0.05). The results of this in vivo study show that GBCAs produce effects that may trigger migraine attacks in migraine. It is recommended that these effects be further investigated and supported by further clinical studies.

Abstract TMP31: Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID): A Potential Neuroprotection Strategy for Acute Ischemic Stroke (AIS) Patients

Background: Despite advances in intravenous thrombolysis and endovascular thrombectomy, numerous acute ischemic stroke survivors continue to experience various disability levels. The nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), has been identified as a potential neuroprotective agent against ischemic damage. This study evaluates the safety and preliminary efficacy of intravenous GTN administration in AIS patients. Methods: We conducted a prospective, double-blind, randomized controlled trial at Beijing Luhe Stroke Center (ChiCTR2100046271). AIS patients within 24 hours of onset were evenly divided into GTN or control groups (n=20 each). The GTN group received intravenous GTN (5 mg in 50 ml saline at a rate of 0.4 mg/h for 12.5 h/day over 2 days), while controls were administered an equivalent volume of 0.9% saline. Both groups followed standard Stroke Guidelines for treatment. Safety measures focused on SBP&lt;110mmHg and headache occurrence. Efficacy was assessed via the 90-day modified rankin scale (mRS) and the national institutes of health stroke scale (NIHSS) scores. Results: Of the 40 AIS patients, baseline characteristics such as age, gender, risk factors, and mRS scores showed no significant difference between the groups. Safety measures of SBP&lt;110mmHg and headache occurrence were also comparable. Overall, 90-day mRS(1 vs 1) and NIHSS (1 vs1 )did not significantly differ between groups. However, the GTN-treated group showed a superior NIHSS recovery (ΔNIHSS 4.5 Vs 3, p=0.028), indicating that GTN can well-allow patients to recover within the same time frame. Subgroup analyses revealed a noteworthy benefit of GTN in the 90-day NIHSS score for non-thrombolysis patients (1 vs 2, p=0.016). Moreover, GTN benefited mild stroke patients (NIHSS score &lt;6) at 90 days (p=0.025). Conclusion: The RIGID study confirms the safety of intravenous GTN for AIS patients. Notably, while overall 90-day mRS and NIHSS scores between the GTN and control groups did not significantly vary, the GTN group displayed a pronounced improvement in NIHSS recovery. Additionally, GTN demonstrated particular efficacy for non-thrombolysis patients and those with mild stroke symptoms, suggesting its potential as a tailored intervention in specific AIS subgroups.

Abstract 27: A Novel Adjuvant Strategy After Endovascular Therapy: Arterial Glyceryl Trinitrate in Acute Ischemic Stroke for Neuroprotection (AGAIN)

Introduction: Although mechanical thrombectomy (MT) demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. The protective effect of NO donors has been shown to prevent ischemia-reperfusion injury through reduction of reactive oxygen species formation in cardiovascular studies. Glyceryl Trinitrate (GTN), a Food and Drug Administration-approved vasodilator, is one of the widely used exogenous NO donors used in the clinic and has been trialed for neuroprotection in AIS without successful clinical translation. The recent advances in MT for AIS have paved the way for promising new opportunities to supplementary neuroprotective therapies to patients after reperfusion. This study evaluated the safety, feasibility, and preliminary efficacy of intra-arterial administration of GTN after MT for neuroprotection. Methods: This is a prospective randomized controlled study (ID: ChiCTR2100045254). Eligible patients were randomized to receive 800μg GTN or same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (sICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). Results: A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. No significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends for both functional independence (mRS 0-2, 75.0% vs. 65.0%) at 90 days and reduction in final infarct volume (33.2 vs. 38.9 ml) have been observed in GTN group, although they did not reach the significant levels. Moreover, the concentration of blood NO X was increased (p&lt;0.05) at 2 hours after GTN administration (26.2 vs 18.0 μmol/l). Conclusion: The AGAIN study suggests intra-arterial administration of GTN post MT is safe and feasible in AIS patient. The discernible positive trends may be due to the raised NO X levels, which potentially highlight the mechanistic reinforcement for these observed benefits.

Regulation of headache response and transcriptomic network by the trigeminal ganglion clock.

To characterize the circadian features of the trigeminal ganglion in a mouse model of headache. Several headache disorders, such as migraine and cluster headache, are known to exhibit distinct circadian rhythms of attacks. The circadian basis for these rhythmic pain responses, however, remains poorly understood. We examined trigeminal ganglion exvivo and single-cell cultures from Per2::LucSV reporter mice and performed immunohistochemistry. Circadian behavior and transcriptomics were investigated using a novel combination of trigeminovascular and circadian models: a nitroglycerin mouse headache model with mechanical thresholds measured every 6 h, and trigeminal ganglion RNA sequencing measured every 4 h for 24 h. Finally, we performed pharmacogenomic analysis of gene targets for migraine, cluster headache, and trigeminal neuralgia treatments as well as trigeminal ganglion neuropeptides; this information was cross-referenced with our cycling genes from RNA sequencing data to identify potential targets for chronotherapy. The trigeminal ganglion demonstrates strong circadian rhythms in both exvivo and single-cell cultures, with core circadian proteins found in both neuronal and non-neuronal cells. Using our novel behavioral model, we showed that nitroglycerin-treated mice display circadian rhythms of pain sensitivity which were abolished in arrhythmic Per1/2 double knockout mice. Furthermore, RNA-sequencing analysis of the trigeminal ganglion revealed 466 genes that displayed circadian oscillations in the control group, including core clock genes and clock-regulated pain neurotransmitters. In the nitroglycerin group, we observed a profound circadian reprogramming of gene expression, as 331 of circadian genes in the control group lost rhythm and another 584 genes gained rhythm. Finally, pharmacogenetics analysis identified 10 genes in our trigeminal ganglion circadian transcriptome that encode target proteins of current medications used to treat migraine, cluster headache, or trigeminal neuralgia. Our study unveiled robust circadian rhythms in the trigeminal ganglion at the behavioral, transcriptomic, and pharmacogenetic levels. These results support a fundamental role of the clock in pain pathophysiology. Several headache diseases, such as migraine and cluster headache, have headaches that occur at the same time each day. We learned that the trigeminal ganglion, an important pain structure in several headache diseases, has a 24-hour cycle that might be related to this daily cycle of headaches. Our genetic analysis suggests that some medications may be more effective in treating migraine and cluster headache when taken at specific times of the day.

Outcomes of non-surgical treatment of chronic anal fissure: A comparative study

Background and objective: Chronic anal fissure is a common health problem related to high morbidity. The chemical option for treating chronic anal fissures is highly preferred. Methods: A clinical prospective comparative study was carried out in the General Surgery Outpatient Department in Rizgary Teaching Hospital, Erbil, KRG, during the period from January 2019 to December 2021,on a sample of 100 patients randomly recruited patients with chronic anal fissures divided into two groups with 50 participants each: the DTZ group, who received 2% diltiazem ointment, and the GTN group, who used 0.2% glyceryl trinitrate ointment twice daily for 6 consecutive weeks. The aim of the study is to compare the efficacy and effects of topical Diltiazem (DTZ) and topical glyceryl trinitrate (GTN) in the management of chronic anal fissures. Results: There was a highly significant association between fissure healing at the 4th week and patients treated with DTZ (P &lt;0.001). A highly significant association was observed at the 6th week between fissure healing and DTZ treatment (P &lt;0.001), while there was later a highly significant association between fissure healing at the 8th week and patients treated with GTN (P &lt;0.001). A significant association was observed between treatment adverse effects and patients treated with GTN (P = 0.05). DTZ was found to be more effective for symptomatic relief than GTN. Conclusion: Both DTZ and GTN are effective in the treatment of chronic anal fissures, but treatment with DTZ is accompanied by faster healing and lower side effects.

Distal radial approach using a transdermal nitroglycerin patch : double-blinded randomized trial

Abstract Background The distal radial approach (DRA) provides a lower risk of radial artery occlusion than the conventional transradial approach (TRA) and has recently been used worldwide as an alternative access route for coronary catheterization. However, the small diameter of the distal radial artery causes difficulty in puncture and leads to DRA failure. Purpose The aim of this study is to elucidate whether a transdermal nitroglycerin patch improves the rate of successful DRA cannulation. Methods A total of 92 patients with angina pectoris scheduled for elective coronary angiography via DRA randomly received (1:1) a transdermal nitroglycerin patch pre-integrated with the covering material or only the covering material on their upper arm on the side of the puncture. The diameter of the distal radial artery was evaluated with ultrasound at baseline and after application. DRA procedures were performed in a double-blinded fashion. The primary outcome was the rate of successful palpation-guided distal radial artery cannulation with the first puncture. Results The nitroglycerin group had larger distal radial artery diameter after patch application than the no-treatment group (3.21 ± 0.68 mm vs. 2.71 ± 0.52 mm, P&amp;lt;0.001), but not at baseline (2.64 ± 0.48 mm vs. 2.64 ± 0.45 mm, P = 0.965, Figure 1).The nitroglycerin group had a significantly higher success rate of palpation-guided DRA cannulation with the first puncture than the no-treatment group (58.7% vs. 23.9%; P = 0.001; odds ratio, 4.5; 95% confidence interval, 1.9–11.0, Figure 2). Fewer punctures were required for successful sheath insertion in the nitroglycerin group compared with the no-treatment group (1 [1–5] vs. 3 [2–6]; P=0.019). Procedure time from puncture to sheath insertion was shorter in the nitroglycerin group, but the difference was not significant (142 [112–287] seconds vs. 202 [142–411] seconds; P=0.058). The incidence of vasospasm, hypotension (systolic blood pressure &amp;lt; 90 mmHg) before and during CAG, and puncture site hematoma was similar in the two groups. No patients experienced distal radial arterial occlusion. Conclusions The use of a transdermal nitroglycerin patch was associated with an increase in the diameter of the distal radial artery, higher success rate of DRA cannulation with the palpation-guided first puncture. The transdermal nitroglycerin patch has a potential to be an effective pretreatment for DRA.Changes in distal radial artery diameterResults of primary outcome

Arterial Glyceryl Trinitrate in Acute Ischemic Stroke After Thrombectomy for Neuroprotection (AGAIN): A Pilot Randomized Controlled Trial

Although endovascular therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. This study aimed to evaluate the safety, feasibility, and preliminary efficacy of intra-arterial administration of glyceryl trinitrate (GTN) after endovascular recanalization for neuroprotection. This is a prospective randomized controlled study. Eligible patients were randomized to receive 800 μg GTN or the same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (ICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. Additionally, no significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends, while non-significant, were noted in both outcome and imaging for functional independence at 90 days and reduction in final infarct volume (75.0% vs 65.0%; 33.2 vs 38.9 ml) for the GTN group. Moreover, the concentration of blood NOx in the GTN group was significantly higher than in the control group at 2 h after GTN administration (26.2 vs 18.0 μmol/l, p < 0.05). The AGAIN study suggests intra-arterial administration of GTN post-endovascular therapy is safe and feasible and GTN successfully raised NOx levels over controls at 2 h. A multi-center randomized controlled trial with a larger sample size is warranted to determine GTN neoadjuvant efficacy.

Regulatory role of phospholipase A2 inhibitor in oxidative stress and inflammation induced by an experimental mouse migraine model

Migraine is a complex neurological problem whose primary symptom is headache and is common in the human population. It is well known that neuroinflammation plays a vital role in the pathogenesis of migraine, with adverse effects on the nervous system, including headache disorders such as migraine. The infusion of the nitric oxide donor glyceryl trinitrate (GTN) is often used in experimental models of migraine because it is the best-known model of migraine provocation. N-(p-amyl cinnamoyl) anthranilic acid (ACA) has been shown to inhibit both TRPM2 and phospholipase A2 (PLA2). Recent research has explored potential interventions to mitigate GTN-induced neurotoxicity. One such candidate is ACA, a compound with anti-inflammatory and antioxidant properties.&#x0D; Thirty-six C57BL/6j black mice were divided into the control groups of ACA, GTN, and ACA+GTN. Mice in the ACA were treated intraperitoneally with ACA (25 mg/kg) for three days. Mice in the GTN were treated intraperitoneally with a single dose of GTN (10 mg/kg) for migraine induction. After the experimental stages were completed, the mice in all groups were sacrificed, and brain tissue and erythrocyte samples were taken from the mice.&#x0D; The levels of inflammatory cytokines (TNF α, IL 1β, and IL 6), apoptosis, intracellular ROS, lipid peroxidation, caspase 3-9, and mitochondrial membrane potential increased in the GTN group. However, their levels were decreased in the ACA+GTN group by the injection of ACA. The treatment of ACA regulated the GTN treatment-induced decreases of glutathione levels, glutathione peroxidase activation, and cell viability in the brain and erythrocytes.&#x0D; In conclusion, GTN plays a role in neurotoxicity caused by increased apoptosis and ROS. We observed that ACA modulated the brain and erythrocyte oxidant, antioxidant parameters, and apoptotic processes. The neuro-protective role of ACA treatment may be explained by its modulating activity against increased apoptosis and oxidative stress.

Effect of Nitric Oxide Donors on Uterine and Subendometrial Blood Flow in Patients with Unexplained Infertility: A Randomized Controlled Trial

Unexplained infertility has been defined, by the Practice Committee of the American Society of Reproductive Medicine (ASRM), as inability of a couple to conceive for at least 12 months, with unremarkable standard infertility evaluation ((ASRM), 2006). Although estimates vary, the prevalence of unexplained infertility is approximately 15–30% Aim of the Work to evaluate the effect of nitroglycerine transdermal patches on uterine and subendometrial blood flow in women with unexplained infertility. Patients and Methods Transdermal nitroglycerine patch was administered to the allocated group from the 2nd day of cycle till maturation of the follicles ≥ 18 mm just for one cycle. Results The relatively underdeveloped endometrial thickness did not change significantly after treatment of women with unexplained infertility with nitroglycerin and remained significantly lower than women of the fertile group. Also, nitroglycerin treatment did not result in significant change in uterine artery Doppler indices. However, uterine artery indices of nitroglycerin-treated women did not also show a significant difference (P &amp;gt; 0.05) from fertile women. On the contrary, nitroglycerin treatment in women with unexplained infertility significantly increased subendometrial 3D power Doppler indices to mean values that did not differ significantly from the fertile women. According to the results of the current study, biochemical pregnancy was more commonly achieved in the nitroglycerin group compared to the control group (6.67% vs 3.33%), Yet this difference failed to prove statistical significance. Although adverse effects of nitroglycerin treatment in the current study, namely headache, blurring of vision and hypotension, were more common on the nitroglycerin group compared to the control and fertile groups; this difference couldn’t reach statistical significance (P &amp;gt; 0.05). Conclusion Doppler study of uterine hemodynamics can be considered in infertility work-up. Although still lacking evidence, women with suboptimal uterine perfusion may be offered therapies improving uterine blood flow, such as nitroglycerin.

The Impact of Nitroglycerin on the Evaluation of Coronary Stenosis in Coronary-CT: Preliminary Study in 131 Patients.

The sublingual administration of short-acting nitroglycerin (NTG) before coronary computed tomography (CCT) improves the visualization of coronary arteries, causing vasodilatation. The aim of this study was to evaluate whether and how nitroglycerin can influence the concordance between radiologists and cardiologists in the evaluation of vessel stenosis measured in CCT by the former and during the following coronarography by the latter. We conducted a retrospective analysis of 131 patients who underwent CCT for cardiac symptoms in 2022, followed by coronarography performed six months later because of significant stenosis revealed by the CCT. First, the patients were divided into two groups: an NTG group who received sublingual nitroglycerin before CCT and a non-NTG group who did not because of contraindications. Second, 254 stenoses were measured by two radiologists after CCT and by two interventional cardiologists during the next coronarography; moreover, stenoses were classified on the basis of their location and plaque pattern (calcific, mixed and lipidic). Third, the strength of agreement was evaluated between the two radiologists, between the two cardiologists and finally between the radiologists and cardiologists in order to evaluate whether and how the interdisciplinary discrepancy in stenosis evaluation could change with or without the use of nitroglycerin before CCT and in relation to the different plaque pattern. In the NTG group, the use of nitroglycerine reduced the agreement between radiologists and cardiologists in calcific stenosis but did not change the concordance in the case of mixed or lipidic plaques on the same vessels. The use of sublingual nitroglycerin before CCT may lead to a radiological overestimation of calcific stenosis.

Distal Radial Approach in Coronary Angiography Using a Transdermal Nitroglycerin Patch: Double-Blinded Randomized Trial

Nitroglycerin dilates the radial artery and prevents spasm, which increases the success rate of sheath cannulation through the conventional transradial approach. However, the effects of nitroglycerin on distal radial approach (DRA) procedures are not known. The aim of this study is to elucidate whether a transdermal nitroglycerin patch improves the rate of successful DRA cannulation. A total of 92 patients scheduled for coronary angiography by means of DRA randomly received (1:1) a transdermal nitroglycerin patch preintegrated with the covering material or only the covering material on their upper arm on the side of the puncture. The diameter of the distal radial artery was evaluated with ultrasound at baseline and after application. DRA procedures were performed in a double-blind fashion. The primary outcome was the rate of successful palpation-guided distal radial artery cannulation with the first puncture. The nitroglycerin group had larger distal radial artery diameter after patch application than that of the no-treatment group (mean, 3.21 mm vs 2.71mm, p <0.001), but not at baseline (mean, 2.64 mm vs 2.64mm, p=0.965).The nitroglycerin group had a significantly higher success rate of DRA cannulation with the first puncture than that of the no-treatment group (59% vs 24%, p=0.001; odds ratio 4.5, 95% confidence interval 1.9 to 11.0). The nitroglycerin group required fewer punctures than did the no-treatment group (median, 1 vs 3, p=0.019). There were no significant differences in the occurrence of hypotension between the 2 groups. No patients experienced radial artery occlusion. In conclusion, transdermal nitroglycerin patch application safely facilitates DRA cannulation. Trial Registration: Japan Registry of Clinical Trials, https://jrct.niph.go.jp/ (identifier: jRCTs051210128).

Improving the visualisation of perforator arteries for anterolateral thigh flaps harvest in CT angiography via sublingual glyceryl trinitrate

To investigate the improvement of image quality and visualisation of the anterolateral thigh (ALT) flap perforators on computed tomography angiography (CTA) after administration of sublingual glyceryl trinitrate (GTN). Sixty patients with oral lesions received thigh CTA examinations were divided randomly into two groups after administration of sublingual GTN (GTN group) or without administration of sublingual GTN (non-GTN group). Two radiologists calculated the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and assessed the image quality of each vessel. Besides, the grade of thigh artery, the lumen diameter of deep femoral artery, lateral circumflex femoral artery (LCFA), the descending branch of LCFA and its proximal and distal perforators, and the number and type of visible perforators were evaluated quantitatively. The SNR and CNR were not significantly different between the two groups (p>0.05). The image quality of CTA in the GTN group was significantly better than that in the non-GTN group (p<0.01). The lumen diameters of the deep femoral artery, LCFA, the descending branch of LCFA and its perforators were significantly larger in the GTN group than those in the non-GTN group (p<0.01). Compared with the non-GTN group, the number of visible perforators and the number of visible septocutaneous perforators were significantly more in the GTN group, and the qualitative grade of visible perforators was significantly higher (p<0.001). The administration of sublingual GTN in preoperative thigh CTA can improve the image quality and visualisation of perforator vessels, thus could help surgeons to select the optimum ALT flaps.

Levcromakalim provokes an acute rapid-onset migraine-like phenotype without inducing cortical spreading depolarization

BackgroundMigraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking aura-like symptoms in migraineurs. We investigated whether single LVC injection causes acute migraine-like phenotype in rats and induces/modulates cortical spreading depolarization (CSD), a rodent model of migraine aura.MethodsWistar rats were administered LVC (1 mg/kg, i.p.) and compared to control (CTRL, vehicle, i.p.) and nitroglycerin (NTG, 10 mg/kg, i.p.) groups. Von Frey filaments were used to examine the periorbital and hind paw mechanical allodynia. Dark–light box (DLB), elevated plus maze (EPM), and open field arena (OFA) were used to evaluate light sensitivity and anxiety-related behaviors. The effects of LVC on CSD parameters, somatosensory evoked potentials, and baseline dural EEG (electroencephalography) were investigated. Possible CSD-induced c-fos expression was studied with Western Blot. Blood–brain barrier integrity in cortex was examined with Evans blue assay.ResultsLVC and NTG administration robustly reduced periorbital mechanical thresholds in rats and induced anxiety-like behaviors and photophobia within 30 and 120 min, respectively. LVC induced migraine-like phenotype recovered in 2 h while NTG group did not fully recover before 4 h. Both LVC and NTG did not provoke DC (direct current) shift, EEG alterations or cortical c-fos expression characteristic to CSD. LVC did not induce de novo CSD and affect KCl (potassium chloride)-induced CSD parameters except for an increase in propagation failure. However, NTG significantly increased both CSD susceptibility and propagation failure. Somatosensory evoked potential (SSEP) configurations were not altered in both LVC and NTG groups, but SSEP latencies were prolonged after CSD. Acute LVC or NTG injection did not increase cortical BBB permeability.ConclusionsSingle LVC administration induced the fastest manifestation and recovery of acute migraine-like phenotype which was not mediated by CSD waves in the cerebral cortex. We suppose LVC triggered rapid-onset migraine-like symptoms are probably related to functional alterations in the trigeminal nociceptive system and K+ channel opening properties of LVC. Understanding the neurobiological mechanisms of this nociceptive window, may provide a novel target in migraine treatment.

Fructose supplementation shifts rat brain metabolism in experimental migraine

AimsWe have previously demonstrated that fructose supplementation (FS), given in a scheme used for inducing metabolic syndrome (MS), elicited pain relief in the nitroglycerin (NTG)-elicited rat migraine model. Herein, we evaluated whether FS could reestablish the impaired metabolic pathways in NTG-injected rats. Main methodsMale Wistar rats (N = 40) were divided into two groups for receiving 10 % FS or tap water. After 45 days, they were subdivided into NTG-injected (10 mg/kg; 15 days) or controls. After the fourth NTG injection, 18F-fluorodeoxyglucose ([18F] FDG) micro-PET scanning was accomplished. The day after, euthanasia was performed, and blood was collected for glycemia and LDH analysis. The levels of energy molecules, TBARS, PGC-1α, and MCTS1 were evaluated in the brain cortices. The activated satellite glial cells (SGC) were assessed in the trigeminal ganglion (TG). Key findingsThere were no variations of glycemia or LDH serum levels. NTG-injected rats showed a significant increase in glucose uptake in the hypothalamus (HT) vs. NTG-free rats. The FS-NTG group showed increased metabolism in the superior colliculus (SC) vs. the NTG group. Moreover, the glucose uptake was amplified in the inferior colliculus (IC) of the FS-NTG vs. FS group. The cortical inosine levels were significantly higher in FS-NTG rats vs. NTG or FS groups, with no changes in TBARS or MCTS1 levels, despite a minor decrease of PGC1-α contents in the FS+NTG group. Finally, there was a significant increase of activated SGC around TG in the FS-NTG rats. SignificanceWe provide novel evidence linking nutrition and metabolism with migraine.