Administration Of Nitroglycerin Research Articles

Intra-Arterial Labetalol and Nitroglycerin in Preventing Radial Artery Spasm Following Transradial Angiography: A New Approach

Background: Radial artery spasm (RAS) resulted from decreasing blood flow and activation of vasomotor system leads to a decrease in artery diameter, perfusion and patency, and increase the risk of procedure failure. In this study, we investigated the effects of intra-arterial administration of nitroglycerin and labetalol on radial artery diameter, RAS, and pain intensity in patients undergoing diagnostic radial angiography. Methods: Sixty-four patients randomly enrolled into one of the nitroglycerin (150 μg) or labetalol (500 μg) groups. The radial artery size, and the incidence of RAS were measured before, immediately after puncture, and at the end of treatment. Pain intensity was evaluated using a visual-analog-scale (VAS) at the end of the procedure. Hemodynamic status before, and during the procedure was also recorded. Results: Labetalol causes a significantly larger increase in radial diameter than nitroglycerin immediately after intra-arterial injection (2.24±0.58 mm vs. 1.65±0.39 mm, P-value<0.001). The rate of RAS immediately after vasodilator administration in the labetalol group was 3.1% vs. 12.5% in the nitroglycerin group (P-value=0.355), but the overall incidence (immediately after administration+ at the end of procedure) did not show a statistically significant difference (53.125% vs 31.25% respectively, P-value=0.076). The VAS score did not show a significant difference between two groups (1.15±0.44 in nitroglycerin vs. 1.50±0.91, P-value=0.063). Conclusion: Labetalol increases radial artery diameter more than nitroglycerin. However, the efficacy of labetalol in terms of RAS incidence, and patients’ pain was similar to nitroglycerin. Therefore, intra-arterial labetalol could be considered as one of the therapeutic options in clinical practice in order to reduce RAS and procedure failure.

Effects of Land versus Water Walking Interventions on Vascular Function in Older Adults.

Endothelial dysfunction is an early and integral atherogenic event. Interventions that improve endothelial function also reduce cardiovascular risk. Due largely to the direct hemodynamic effects of repetitive exercise on the artery wall, exercise training has shown to enhance endothelial function. Land walking (LW) and water walking (WW) induce distinct hemodynamic responses, so the comparison of their effects provides an approach to study shear stress effects on endothelial function. We hypothesized that LW and WW training would have different effects on peripheral artery endothelial function. Fifty-one sedentary, older (age = 61.9 ± 6.6 yr, 23.5% male) individuals were randomized into one of three groups: control (n = 16), or one of two exercise groups consisting of 3 × 50 min supervised and individually tailored walking sessions per week for 24 consecutive weeks, performed either on LW (n = 17) or on WW (n = 18). Brachial artery endothelial function (flow-mediated dilation) and smooth muscle cell function (glyceryl trinitrate administration) were tested in all participants before (week 0) and after (week 24) the intervention. Differences were apparent in flow-mediated dilation change between the LW group (week 0, 5.39% ± 0.71%, to week 24, 7.77% ± 0.78%; P = 0.009) and the control group (week 0, 5.87% ± 0.73%, to week 24, 5.78% ± 0.78%). No differences in artery dilation response were found after glyceryl trinitrate administration (all P > 0.05). This study suggests that 6-month center-based LW may be superior to WW in terms of improvement in arterial endothelial function in older sedentary individuals.

Nitroglycerin Plus Morphine on Iv Patient Controlled Analgesia for Abdominal Surgery: The Effect on Postoperative Pain.

BackgroundSome studies have reported the effect of nitroglycerin on the reduction of pain after surgery.ObjectivesThe primary goal of the current study was to evaluate the addition of nitroglycerin (as a nitric oxide donor) to morphine in patient-controlled analgesia. Besides, its effects on the reduction of pain and stability in hemodynamic indices after abdominal surgery are also investigated.MethodsThe current study was performed on 60 patients as candidates for abdominal surgery. Morphine (0.75 mg/mL) and nitroglycerin plus morphine (morphine 0.5 mg/mL + TNG 15 μg/mL) infusions were used for control and case groups, respectively, with the same induction of anesthesia. The severity of postoperative pain, hemodynamic indices of systolic blood pressure, diastolic pressure, heart rate, respiratory rate, and nausea were measured after surgery (immediately, 2, 6, 12, and 24 hours after surgery).ResultsThe pain score decreased for both groups almost similarly. The mean systolic blood pressure was highly reduced in both groups. However, the mean diastolic blood pressure in the control group was considerably lower than that of the case group. Besides, the respiratory rate in the case group dramatically diminished and approached the normal value.ConclusionsCombined administration of nitroglycerin and morphine had no synergistic effects on reducing postoperative pain. However, it led to more stable hemodynamic indices and improved breathing, without any side effects.

Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine

BackgroundVestibular migraine has recently been recognized as a novel subtype of migraine. However, the mechanism that relate vestibular symptoms to migraine had not been well elucidated. Thus, the present study investigated vestibular dysfunction in a rat model of chronic migraine (CM), and to dissect potential mechanisms between migraine and vertigo.MethodsRats subjected to recurrent intermittent administration of nitroglycerin (NTG) were used as the CM model. Migraine- and vestibular-related behaviors were analyzed. Immunofluorescent analyses and quantitative real-time polymerase chain reaction were employed to detect expressions of c-fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and vestibular nucleus (VN). Morphological changes of vestibular afferent terminals was determined under transmission electron microscopy. FluoroGold (FG) and CTB-555 were selected as retrograde tracers and injected into the VN and TNC, respectively. Lentiviral vectors comprising CGRP short hairpin RNA (LV-CGRP) was injected into the trigeminal ganglion.ResultsCM led to persistent thermal hyperalgesia, spontaneous facial pain, and prominent vestibular dysfunction, accompanied by the upregulation of c-fos labeling neurons and CGRP immunoreactivity in the TNC (c-fos: vehicle vs. CM = 2.9 ± 0.6 vs. 45.5 ± 3.4; CGRP OD: vehicle vs. CM = 0.1 ± 0.0 vs. 0.2 ± 0.0) and VN (c-fos: vehicle vs. CM = 2.3 ± 0.8 vs. 54.0 ± 2.1; CGRP mRNA: vehicle vs. CM = 1.0 ± 0.1 vs. 2.4 ± 0.1). Furthermore, FG-positive neurons was accumulated in the superficial layer of the TNC, and the number of c-fos+/FG+ neurons were significantly increased in rats with CM compared to the vehicle group (vehicle vs. CM = 25.3 ± 2.2 vs. 83.9 ± 3.0). Meanwhile, CTB-555+ neurons dispersed throughout the VN. The structure of vestibular afferent terminals was less pronounced after CM compared with the peripheral vestibular dysfunction model. In vivo knockdown of CGRP in the trigeminal ganglion significantly reduced the number of c-fos labeling neurons (LV-CGRP vs. LV-NC = 9.9 ± 3.0 vs. 60.0 ± 4.5) and CGRP mRNA (LV-CGRP vs. LV-NC = 1.0 ± 0.1 vs. 2.1 ± 0.2) in the VN, further attenuating vestibular dysfunction after CM.ConclusionsThese data demonstrates the possibility of sensitization of vestibular nucleus neurons to impair vestibular function after CM, and anti-CGRP treatment to restore vestibular dysfunction in patients with CM.

P0677CONTRAST-ENHANCED ULTRASOUND TO ASSESS RENAL MICROCIRCULATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Vascular factors such as capillary rarefaction, increased vascular stiffness and reduced vasodilatation due to endothelial dysfunction probably play an important role in the pathophysiology of chronic kidney disease (CKD). However, our understanding of the underlying mechanisms is hampered by the lack of non-invasive techniques to quantify renal microvasculature in humans. The aim of this study was to assess whether contrast-enhanced ultrasonography (CEUS) can identify (1) differences in renal microcirculation and (2) the degree of nitroglycerin-induced vasodilatation (NIV) as a measure of renal flow reserve between CKD-patients and age-matched healthy volunteers. Method All participants underwent CEUS under standardized conditions. Sonovue© (0.015 ml/kg/min) was perfused as contrast agent until a steady state was obtained, followed by four destruction-refilling sequences. Outcome measure of CEUS was the mean (change in) perfusion index (PI) of the outer renal cortex (see figure for an example). In a subgroup of participants, CEUS was repeated before and five minutes after the sublingual administration of nitroglycerin (0.2mg). Renal resistive index (RRI) as a measure of vascular stiffness was also measured at each time point with Doppler ultrasound. Results A total of 38 healthy volunteers (aged 50±8 years, eGFR 95±13 ml/min/1.73 m, 69% women) and 18 CKD stage 2-3 patients (aged 55±15 years, eGFR 64±32 ml/min/1.73m, 56% women) were included. Renal PI was significantly lower in CKD patients (1304±762 vs 2989 ±2503 arbitrary units, p=0.034), whereas RRI did not differ (0.66± 0.07 vs 0.63± 0.04), p=0.10). PI was lower in CKD due to vascular nephropathy (n=3) or interstitial nephritis (n=4) than CKD due to diabetes (n=4) or other causes (7). In continuous analysis, PI correlated with eGFR (spearman’s r=0.54, p=0.005) but not with blood pressure. Renal PI did not change after nitroglycerin in both groups; RRI decreased in healthy (from 0.64±0.03 to 0.61±0.02, p=0.01) but not in CKD patients. Conclusion In this study, contrast-enhanced ultrasound identified important alterations in renal microperfusion in patients with moderate CKD. Whether a low perfusion index predicts renal function decline needs further study. Sublingual nitroglycerin seems to have limited potential as a new test of renal flow reserve.

Analysis of Providing Emergency Care to Patients with Myocardial Infarction without ST Segment Elevation

A high mortality rate due to acute myocardial infarction (AMI) stimulates the analysis of the quality of emergency medical care at the prehospital stage. Firstly, an analysis of the reasons for the treatment of patients with AMI to general practitioners is necessary. Secondly, the quality of the provision of medical services by general practitioners is one of the criteria for the effectiveness of the implementation of patient management protocols, which requires a systematic analysis and relevant studies.The objective: to analyze the provision of emergency medical care to patients with acute myocardial infarction without ST segment elevation (NSTEMI) when they seek medical care.Materials and methods. The referral routes for hospitalization of patients with acute coronary syndrome and clinical manifestations were analyzed among 280 patients with STEMI and 91 patients with NSTEMI. The assessment of treatment tactics in patients with NSTEMI was carried out in the following paragraphs of the emergency medical care protocol: determination of blood saturation, ensuring reliable venous access, administration of nitroglycerin in aerosol (1–2 doses or 0,4–0,8 mg), use of acetylsalicylic acid (ASA ) after chewing 160–325 mg, the use of clopidogrel 300 mg orally; the appointment of β-blocker; narcotic analgesic; anticoagulant. Statistical data processing was carried out using non-parametric criterion χ2.Results. Appeals to primary health care centers were significantly more frequent in patients with NSTEMI, due to the clinical course of the disease.Conclusion. At the stage of medical care by general practitioners, only the appointment of acetylsalicylic acid met the criteria for the implementation of the protocol for the provision of emergency medical care to patients with NSTEMI.

Аналіз надання екстреної медичної допомоги хворим на інфаркт міокарда без елевації сегмента ST при звернені по медичну допомогу

A high mortality rate due to acute myocardial infarction (AMI) stimulates the analysis of the quality of emergency medical care at the prehospital stage. Firstly, an analysis of the reasons for the treatment of patients with AMI to general practitioners is necessary. Secondly, the quality of the provision of medical services by general practitioners is one of the criteria for the effectiveness of the implementation of patient management protocols, which requires a systematic analysis and relevant studies.The objective: to analyze the provision of emergency medical care to patients with acute myocardial infarction without ST segment elevation (NSTEMI) when they seek medical care.Materials and methods. The referral routes for hospitalization of patients with acute coronary syndrome and clinical manifestations were analyzed among 280 patients with STEMI and 91 patients with NSTEMI. The assessment of treatment tactics in patients with NSTEMI was carried out in the following paragraphs of the emergency medical care protocol: determination of blood saturation, ensuring reliable venous access, administration of nitroglycerin in aerosol (1–2 doses or 0,4–0,8 mg), use of acetylsalicylic acid (ASA) after chewing 160–325 mg, the use of clopidogrel 300 mg orally; the appointment of β-blocker; narcotic analgesic; anticoagulant. Statistical data processing was carried out using non-parametric criterion χ2.Results. Appeals to primary health care centers were significantly more frequent in patients with NSTEMI, due to the clinical course of the disease.Conclusion. At the stage of medical care by general practitioners, only the appointment of acetylsalicylic acid met the criteria for the implementation of the protocol for the provision of emergency medical care to patients with NSTEMI.

Diabetes Attenuates the Increase in Estrogen‐Mediated Endothelial Function

BackgroundApparently healthy premenopausal women are protected against cardiovascular disease (CVD) compared to men; and estrogen has been thought to play a key role. In the presence of diabetes; however, this overall sex‐dependent cardiovascular protection is lost. The increase in vascular function throughout the menstrual cycle in healthy premenopausal women has been established. The present investigation sought to test the hypothesis that the increase in vascular function from menses to the late follicular phase of the menstrual cycle is lost in premenopausal women with type 1 diabetes (T1D).MethodsPremenopausal women with a clinical diagnosis of T1D (n=22, HbA1c=8.2±1.7%, age=26±8 years, BMI=26.9±5.4 kg/m2) and seemingly healthy, age‐ and sex‐matched controls (n=10, HbA1c=5.2±0.3%, age=26±9 years, BMI=23.3±4.1 kg/m2) were recruited to participate. Flow mediated dilation (FMD), a measure of endothelial function, was assessed during the menses (cycle day=4±1) and late follicular phases (cycle day=13±1) of the menstrual cycle to represent periods of low and high concentrations of estrogen, respectively. Visit 1 (menses) was confirmed by a positive hemolytic urological multistix test and visit 2 (late follicular) was scheduled based on indications from an ovulation prediction kit. A small venous blood sample was collected at each visit to measure concentrations of estrogen. Endothelial independent vasodilation was determined by administration of sublingual nitroglycerin after each FMD test.ResultsThe increase in estrogen from menses to the follicular phase was similar (p=0.73) in both groups (Δ estrogen: T1D=78.3±92.6 vs Controls=85.6±30.0 pg/mL). Baseline brachial artery diameter was similar between T1D and controls (p=0.25) and was not different between visit 1 and visit 2 (p=0.76). Fasting blood glucose was higher (p<0.01) in women with T1D compared to controls at both visits; however, the change within groups was similar (p=0.49) across time. A near significant interaction (p=0.07) for endothelial function was observed such that FMD increased from the menses to follicular phase in controls (ΔFMD=1.151±1.603%), whereas no change was observed in patients with T1D (ΔFMD=−0.633±2.126%). Endothelial independent vasodilation was not different between groups (p=0.82). Additionally, the endothelial independent response was similar across the menstrual cycle (p=0.97).ConclusionThese data suggest that the presence of diabetes may attenuate the beneficial effects of estrogen on endothelial function in premenopausal women. The loss of estrogen’s cardiovascular protective effect on the vasculature in diabetes may explain the increased risk of CVD observed in women with T1D.Support or Funding Information1RO1HL137087‐01A1.

Applying Nitroglycerin at Coronary MR Angiography at 1.5 T: Diagnostic Performance of Coronary Vasodilation in Patients with Coronary Artery Disease.

To evaluate the influence of applying nitroglycerin (NTG) on detecting significant coronary artery disease (CAD) and NTG-induced coronary vasodilation using coronary MR angiography in patients suspected of having CAD. In this prospective study conducted from November 2017 to September 2018, 70 consecutive participants suspected of having CAD were recruited. Of those, 57 patients successfully underwent pre- and post-NTG coronary MR angiography, both of which were performed during the end-systolic phase of the cardiac cycle. Significant coronary stenosis was defined at x-ray coronary angiography as stenosis of 50% or more. Participants were divided into a significant CAD group (significant stenosis) and nonsignificant CAD group (no significant stenosis) based on x-ray coronary angiography. Paired and unpaired Student t, generalized linear mixed model, and McNemar tests were used. The diagnostic performance of coronary MR angiography was significantly improved after NTG (P < .001). Per-patient for coronary MR angiography, from before to after NTG, respectively, the sensitivity was 97.6% (95% confidence interval [CI]: 85.6%, 99.9%) to 97.6% (95% CI: 85.6%, 99.9%), specificity was 25.0% (95% CI: 8.3%, 52.5%) to 62.5% (95% CI: 35.9%, 83.7%), positive predictive value was 76.9% (95% CI: 62.8%, 87.0%) to 87.0% (95% CI: 73.0%, 94.6%), negative predictive value was 80.0% (95% CI: 29.9%, 98.9%) to 90.9% (95% CI: 57.1%, 99.5%), and accuracy was 77.2% (95% CI: 66.3%, 88.1%) to 87.7% (95% CI: 79.2%, 96.3%). The NTG-induced coronary vasodilation was significantly lower in the significant CAD group compared with the nonsignificant CAD group. Administration of NTG significantly improved the diagnostic performance of coronary MR angiography for detecting significant CAD; however, NTG-induced coronary vasodilation was impaired in patients with significant CAD.© RSNA, 2020See also commentary by François in this issue.

Feasibility of Coronary Computed Tomography Angiography Assessment of Explanted Donor Hearts

In the United Kingdom, coronary angiography is rarely performed of donation after brain death donors. Currently up to 30% of potential donor hearts are not utilised due to potential but unconfirmed coronary disease. For Donation After Circulatory death donors, coronary angiography is prohibited, as are all antemortem interventions. We believe that ex situ coronary CT angiography (CTA) will be logistically more feasible than in situ donor coronary angiography or ex situ coronary angiography allowing greater yield of donor hearts. Organ retrieval is performed by direct procurement and perfusion. The aorta of the donor heart is cannulated to allow retrograde perfusion of the heart via the coronary arteries in the setting of a competent aortic valve. Electrocardiographic (ECG) monitoring is performed. The donor heart is paced epicardially to a rate between 70-90 beats per minute as required. Coronary CTA is performed after direct administration of contrast media (iomeron 350) and nitroglycerin administration. Coronary CTA post processing facilitated segmental analysis of all of the coronary arteries with detailed assessment of atherosclerotic plaque burden, plaque morphology and luminal stenosis. Coronary CTA findings are directly compared to histological correlation of plaque burden. Two human cardiac allografts (donation after brain death) were assessed using coronary CTA during ex-vivo perfusion on a local centre ex-vivo perfusion device. Images were reconstructed using Siemens SyngoVia software. In both patients eccentric atherosclerotic plaque burden was quantified using conventional techniques and luminal calibre assessed. Assessment of ex-vivo coronary arteries is feasible using coronary CTA during ex-vivo perfusion of donor hearts. Atherosclerotic plaque and luminal stenosis of ex-vivo coronary arteries can be diagnosed using coronary CTA.

Catheter-induced Multiple Non-proximal Coronary Spasm in a Patient Presenting with Myocardial Infarction

Interventional cardiologists encounter a wide range of lesions that cannot be angiographically distinguished from fixed atherosclerotic obstructive disease. In this case report, we document vasospasm at multiple sites in the coronary territory in a patient presenting with acute coronary syndrome. A 61-year-old woman was referred to our hospital with typical chest pain lasting approximately 1 h. After performing the left coronary artery angiography, a severe tubular stenosis was detected in circumflex (Cx) artery. Diffuse spasm was observed in the right coronary artery (RCA) and it resolved after intracoronary administration of nitroglycerin. After performing left system angiography again, severe stenosis in Cx artery was also completely resolved. Our finding is of clinical importance in that it is more likely to simulate a constant coronary stenosis than would have spasm occurred proximally. The clinical importance of our report is that a catheter-induced vasospasm (CIV) may simulate fixed coronary stenosis, not always osteally and in some instances at multiple sites. Awareness of this phenomenon and liberal use of nitroglycerin in any patient with discrete luminal narrowing, even when an ostial “lesion” is not present, can help to avoid misinterpreting CIV as an atherosclerotic lesion.

Assessment of tissue perfusion and vascular function in mice by scanning laser Doppler perfusion imaging

Post-occlusive reactive hyperemia (PORH) is a key feature of physiological vasomotion to appropriately match the supply/demand ratio of tissues. This adaptive mechanism is severely disturbed in endothelial dysfunction with a reduced flow-mediated dilation (FMD). Reduced PORH and FMD are powerful prognostic risk factors in cardiovascular diseases. While these parameters are frequently determined in human beings, comparable methods applicable to mouse models are sparse. We aimed to evaluate the applicability and accuracy of scanning laser Doppler perfusion imaging (LDPI) to measure PORH in the mouse hindlimb. Changes in mean perfusion in response to vasoactive drugs and PORH (assessed by scanning LDPI) were compared with changes in diameter and blood flow in the femoral artery, as assessed by high-resolution ultrasound. We found that the measured LDPI signal significantly correlated with changes of inflow into the femoral artery. Vasodilation induced by administration of nitroglycerine and acetylcholine increased vessel diameter, blood flow and mean perfusion, while vasoconstriction following administration of epinephrine decreased all three parameters. PORH was induced by temporal occlusion of the femoral artery with an external cuff. During occlusion, mean perfusion decreased to a condition of zero-perfusion and release of the cuff induced an immediate increase in blood flow that was followed by femoral artery dilation driving PORH/perfusion. Surgical removal of the femoral artery decreased mean perfusion to a zero-perfusion level and fully abolished PORH. Importantly, the measurement of the PORH response by scanning LDPI is highly reproducible as determined by repeated measurements and intra/interobserver variation analysis. Last, we found that the PORH response was dependent on nitric oxide synthase and cyclooxygenase and declined with age. Thus, we here provide novel and robust non-invasive methods to serially measure tissue perfusion at baseline and during physiological and pharmacological modulation of vasomotor tone in the hindlimb of mice. The application of these LDPI scanning and ultrasound-based methods may be useful for testing the effects of drugs affecting vasomotor function or future elucidation of mechanisms leading to vasomotor dysfunction in mice in vivo.

What is the optimal duration of the TILT after administration of 0.4 mg nitroglycerin spray?

Performing a head-up tilt test can be of great value for the diagnosis of vasovagal syncope. The European Society of Cardiology recommends a drug challenge phase duration of 15 to 20 minutes, with either Isoprenaline or Nitroglycerin administration.We sought to investigate the outcome of a ten-minute active phase with Nitroglycerin in patients suspected of vasovagal syncope and determine the percentage of loss in the positivity rate, using this short duration approach.We consecutively enrolled patients presenting with syncope undergoing the head-up tilt test (HUTT), with a clinical suspicion of vasovagal syncope between the years 2009 to 2019. The HUTT consisted of 2 successive phases: passive and active. During the passive phase, the patients were tilted at 70° for 20 minutes. If negative, the test was continued after administration of 0.4 mg sublingual Nitroglycerin. Applying the (VASIS) Vasovagal Syncope International Study classification of the vasovagal syncope international study and comparing for age and gender, positive responses were categorized into 3 types.A number of 306 patients (age = 43.5 +/−20.3; male = 140 [45.7%]) with suspected vasovagal syncope, undergoing HUTT, were enrolled in the years of 2009 to 2019. Of those, 245 (80.2%) presented a positive test, with 200 patients (82.0%) during the being positive during the active phase of the test. The results were as follows: 116 subjects (47.2%) presented with a mixed response (VASIS I), 52 (21.3%) showed a cardio inhibitory response (VASIS II), and 77 (31.5%) displayed a vasodepressor response (VASIS III). We found no relationship between the type of syncope with neither gender, nor age of the patient. Three minutes represented the median time to positivity, after Nitroglycerine administration. The time distribution showed a peak incidence appearing between minutes 3 and 5, ranging from 1 to 20 minutes. Only 3 patients tested positive after minute 10.Shortening the active phase to 10 minutes would result in a positivity rate loss of 1.5%.

Evaluation of possible effects of crocin against nitrate tolerance and endothelial dysfunction.

Objective(s):One of the most important problems of taking nitroglycerin is the nitrate tolerance phenomenon and endothelial dysfunction. Oxidative stress is a high-emphasized one of tolerance mechanisms. The possible effect of crocin, one of the anti-oxidant ingredients of saffron, on the nitrate tolerance model was investigated.Materials and Methods:In the present study, lipid peroxidation and the level of activated and deactivated forms of eNOS were measured. Animals were administered subcutaneously with 25 mg/kg of nitroglycerin, twice a day for 3 days to induce nitrate tolerance model. For evaluation of crocin effects, 20, 40 and 80 mg/kg/day of this compound were injected intraperitoneally in concomitant with nitroglycerin. In the isolated aorta test, after preparation of aorta rings, different concentrations of acetylcholine, sodium nitroprusside and nitroglycerin were added to the organ bath after inducing contraction by phenylephrine and the responsiveness of tissues was recorded.Results:Findings showed that nitroglycerin administration caused a remarkable overproduction of malondialdehyde (MDA) in the cells and crocin treatment significantly decreased the MDA level. In the nitrate tolerance group, the level of activated eNOS decreased and the level of deactivated eNOS increased. Crocin partly alleviated these changes: however, its effects were not remarkable. Nitroglycerin injection for 3 days developed tolerance to nitroglycerin and cross-tolerance to acetylcholine (endothelial dysfunction) and sodium nitroprusside. Crocin failed to influence significantly on the nitrate tolerance.Conclusion:Crocin effectiveness is possibly time-dependent; therefore, increasing the duration of treatment with crocin may lead to a significant prevention of nitrate tolerance and endothelial dysfunction.

East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina.

Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH2*1/*1and variantALDH2*2patients with CAD.Methods and Results:The study subjects comprised 55 coronary spastic angina (CSA) patients, confirmed by coronary angiography and intracoronary injection of acetylcholine (42 men and 13 women, mean age 68.0±9.0 years). They underwent NMD and FMD tests in the morning before and after continuous transdermal GTN administration for 48 h. NMD was lower at baseline inALDH2*2than in theALDH2*1/*1group (P=0.0499) and decreased significantly in both groups (P<0.0001 and P<0.0001, respectively) after GTN, with significantly lower levels in theALDH2*2group (P=0.0002). FMD decreased significantly in bothALDH2*1/*1andALDH2*2groups (P<0.0001and P=0.0002, respectively) after continuous GTN administration, with no significant differences between the 2 groups both before and after GTN. Continuous administration of GTN produced endothelial dysfunction as well as nitrate tolerance in bothALDH2*1/1andALDH2*2patients with CSA.ALDH2*2attenuated GTN response and exacerbated GTN tolerance, but not endothelial dysfunction, as compared toALDH2*1/*1in patients with CSA.

3:00 PM Abstract No. 182 Effect of intra-arterial nitroglycerin and verapamil administration during radial artery access on systemic blood pressure and its correlation with timing of moderate sedation administration

3:00 PM Abstract No. 182 Effect of intra-arterial nitroglycerin and verapamil administration during radial artery access on systemic blood pressure and its correlation with timing of moderate sedation administration

Enhanced post-traumatic headache-like behaviors and diminished contribution of peripheral CGRP in female rats following a mild closed head injury.

Females are thought to have increased risk of developing post-traumatic headache following a traumatic head injury or concussion. However, the processes underlying this susceptibility remain unclear. We previously demonstrated the development of post-traumatic headache-like pain behaviors in a male rat model of mild closed head injury, along with the ability of sumatriptan and an anti-calcitonin-gene-related peptide monoclonal antibody to ameliorate these behaviors. Here, we conducted a follow-up study to explore the development of post-traumatic headache-like behaviors and the effectiveness of these headache therapies in females subjected to the same head trauma protocol. Adult female Sprague Dawley rats were subjected to a mild closed head injury using a weight-drop device (n = 126), or to a sham procedure (n = 28). Characterization of headache and pain related behaviors included assessment of changes in cutaneous cephalic and extracephalic tactile pain sensitivity, using von Frey monofilaments. Sensitivity to headache/migraine triggers was tested by examining the effect of intraperitoneal administration of a low dose of glyceryl trinitrate (100 µg/kg). Treatments included acute systemic administration of sumatriptan (1 mg/kg) and repeated systemic administration of a mouse anti-calcitonin gene-related peptide monoclonal antibody (30 mg/kg). Serum levels of calcitonin gene-related peptide were measured at baseline and at various time points post head injury in new cohorts of females (n = 38) and males (n = 36). Female rats subjected to a mild closed head injury developed cutaneous mechanical hyperalgesia, which was limited to the cephalic region and was resolved 4 weeks later. Cephalic pain hypersensitivity was ameliorated by treatment with sumatriptan but was resistant to an early and prolonged treatment with the anti-calcitonin gene-related peptide monoclonal antibody. Following the resolution of the head injury-evoked cephalic hypersensitivity, administration of glyceryl trinitrate produced a renewed and pronounced cephalic and extracephalic pain hypersensitivity that was inhibited by sumatriptan, but only partially by the anti-calcitonin gene-related peptide treatment. Calcitonin gene-related peptide serum levels were elevated in females but not in males at 7 days post head injury. Development of post-traumatic headache-like pain behaviors following a mild closed head injury, and responsiveness to treatment in rats is sexually dimorphic. When compared to the data obtained from male rats in the previous study, female rats display a prolonged state of cephalic hyperalgesia, increased responsiveness to a headache trigger, and a poorer effectiveness of an early and prolonged anti-calcitonin gene-related peptide treatment. The increased risk of females to develop post-traumatic headache may be linked to enhanced responsiveness of peripheral and/or central pain pathways and a mechanism independent of peripheral calcitonin gene-related peptide signaling.

Low-dose interleukin-2 reverses behavioral sensitization in multiple mouse models of headache disorders.

Headache disorders are highly prevalent and debilitating, with limited treatment options. Previous studies indicate that many proinflammatory immune cells contribute to headache pathophysiology. Given the well-recognized role of regulatory T (Treg) cells in maintaining immune homeostasis, we hypothesized that enhancing Treg function may be effective to treat multiple headache disorders. In a mouse model of chronic migraine, we observed that repeated nitroglycerin (NTG, a reliable trigger of migraine in patients) administration doubled the number of CD3 T cells in the trigeminal ganglia without altering the number of Treg cells, suggesting a deficiency in Treg-mediated immune homeostasis. We treated mice with low-dose interleukin-2 (ld-IL2) to preferentially expand and activate endogenous Treg cells. This not only prevented the development of NTG-induced persistent sensitization but also completely reversed the established facial skin hypersensitivity resulting from repeated NTG administration. The effect of ld-IL2 was independent of mouse sex and/or strain. Importantly, ld-IL2 treatment did not alter basal nociceptive responses, and repeated usage did not induce tolerance. The therapeutic effect of ld-IL2 was abolished by Treg depletion and was recapitulated by Treg adoptive transfer. Furthermore, treating mice with ld-IL2 1 to 7 days after mild traumatic brain injury effectively prevented as well as reversed the development of behaviors related to acute and chronic post-traumatic headache. In a model of medication overuse headache, Ld-IL2 completely reversed the cutaneous hypersensitivity induced by repeated administration of sumatriptan. Collectively, this study identifies ld-IL2 as a promising prophylactic for multiple headache disorders with a mechanism distinct from the existing treatment options.

Endovascular Pressure Measurements to Assess the Functional Severity of Mesenteric Arterial Stenoses.

To assess the ability of pressure measurements to discriminate clinically significant celiac artery (CA) or superior mesenteric artery (SMA) stenosis in patients with suspected chronic mesenteric ischemia (CMI). Single-center, retrospective cohort study of 41 intra-arterial pressure measurements during mesenteric angiography with intended revascularization, performed in 37 patients (mean age 67.7 ± 10.8 years, 62% female) between April 2015 and May 2017. Simultaneous prestenotic and poststenotic pressure measurements had been obtained before and after intra-arterial administration of nitroglycerin. Revascularization was performed in 38 of 41 procedures. Definitive diagnosis of CMI was defined as patient-reported symptom relief or improvement after successful revascularization. Pressure gradients obtained after vasodilator administration were significantly higher in CAs and SMAs with ≥50% stenosis. Pressure ratios (pressure distal [Pd]/pressure aorta [Pa]) obtained after vasodilator administration were significantly higher in CAs with ≥50% stenosis. Subgroup analysis of 22 patients with a ≥50% stenosis of either CA or SMA showed significantly higher pressure gradients and Pd/Pa ratios after vasodilator administration in CMI patients (median pressure gradient: CMI [interquartile ratio] 36 [21-40] mm Hg versus no-CMI 20 [9-21] mm Hg, P= 0.041; Pd/Pa: CMI 0.703 [0.598-0.769] versus no-CMI 0.827 [0.818-0.906], P= .009). A ≤0.8 Pd/Pa cutoff value after administration of a vasodilator best identified a clinically relevant stenosis, with 86% sensitivity and 83% specificity. Complications related to the pressure measurements were not observed. Intra-arterial pressure measurements are feasible and safe. Low Pd/Pa ratios were associated with clinically relevant CA or SMA stenosis.

Effect of intracoronary adenosine on ergonovine-induced vasoconstricted coronary arteries.

This study aimed to evaluate the effect of adenosine on epicardial coronary artery diameter during ergonovine provocation testing. A total of 158 patients who underwent an ergonovine provocation test with intracoronary adenosine injection between 2011 and 2014 were selected. Patients were divided into four groups based on the severity of percent diameter stenosis following intracoronary ergonovine administration: Group 1, induced spasm < 50%; Group 2, 50-89%; Group 3, 90-99%; and Group 4, total occlusion. Spasm positivity was observed in 44 (27.8%) cases in the study population (mean age, 57.4 ± ± 10.7 years). Intracoronary adenosine increased the diameter of the ergonovine-induced epicardial artery by 0.51 ± 0.31 mm, 0.73 ± 0.39 mm, 0.44 ± 0.59 mm, and 0.01 ± 0.04 mm in Groups 1, 2, 3, and 4, respectively. Subsequent administration of nitroglycerin further increased vessel diameter by 0.49 ± 0.28 mm, 0.93 ± 0.68 mm, 2.11 ± 1.25 mm, and 2.23 ± 0.69 mm in Groups 1, 2, 3, and 4, respectively. The ratios of adenosine-induced diameter to reference diameter were significantly lower in patients with spasm positive results (0.68 [0.59-0.76] vs. 0.18 [0.00-0.41], p < 0.001 in the study population; 0.60 [0.54-0.67] vs. 0.40 [0.27-0.44], p < 0.001 in Group 2) with the best cut-off value of 0.505 (sensitivity 0.955, specificity 0.921). Intracoronary administration of adenosine dilated the ergonovine-induced vasoconstricted epicardial coronary artery. The ratio of adenosine-induced diameter to reference diameter was significantly lower in patients with spasm positive results.