Administration Of Nitroglycerin Research Articles

Non-Invasive Assessment of Human Microvascular Function in Health and Disease using Incident Dark Field Microscopy.

Reduced peripheral microvascular reactivity is associated with increased risk for major adverse cardiac events (MACE). Tools for non-invasive assessment of peripheral microvascular function are limited and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we utilized a handheld incident-darkfield imaging tool (CytoCam) to test the hypothesis that compared to healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥ 2 risk factors for CAD (Endothelial Dysfunction; ED) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 ED) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to topical application of acetylcholine (Ach) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the ED cohort compared to healthy individuals. Surprisingly, following application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all 3 microvascular perfusion parameters. These results suggest that despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease.

Effects of the Dual FAAH/MAGL Inhibitor AKU-005 on Trigeminal Hyperalgesia in Male Rats.

The inhibition of endocannabinoid hydrolysis by enzymatic inhibitors may interfere with mechanisms underlying migraine-related pain. The dual FAAH/MAGL inhibitor AKU-005 shows potent inhibitory activity in vitro. Here, we assessed the effect of AKU-005 in a migraine animal model based on nitroglycerin (NTG) administration. Male rats were treated with AKU-005 (0.5 mg/kg, i.p.) or vehicle 3 h after receiving NTG (10 mg/kg, i.p.) or NTG vehicle. One hour later, rats were subjected to the open field test followed by the orofacial formalin test. At the end of the test, we collected serum samples for assessing calcitonin gene-related peptide (CGRP) levels as well as meninges, trigeminal ganglia, and brain areas to assess mRNA levels of CGRP and pro-inflammatory cytokines, and endocannabinoid and related lipid levels. AKU-005 reduced NTG-induced hyperalgesia during the orofacial formalin test but did not influence NTG-induced changes in the open field test. It significantly reduced serum levels of CGRP, CGRP, and pro-inflammatory cytokine mRNA levels in the meninges, trigeminal ganglia, and central areas. Surprisingly, AKU-005 caused no change in endocannabinoids and related lipids in the regions evaluated. The present findings suggest that AKU-005 may have anti-migraine effects by reducing CGRP synthesis and release and the associated inflammatory events. This effect, however, does not seem mediated via an interference with the endocannabinoid pathway.

Environmental enrichment alleviates hyperalgesia by modulating central sensitization in a nitroglycerin-induced chronic migraine model of mice

BackgroundChronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM.MethodsA mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated.ResultsRepeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE.ConclusionEE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.

Combination Administration of Heparin and Nitroglycerin for the Treatment of Polycaprolactone-Induced Intravascular Embolism: A Preclinical Investigation.

As a new-generation collagen stimulator, polycaprolactone (PCL) containing filler has been extensively applied in facial dermal fillers and other medical aesthetic fields. However, inadvertent intravascular injection of PCL may result in complications such as tissue edema, flap necrosis, and even blindness. To date, there is no effective treatment for PCL-induced intravascular embolism. The aim of this study was to identify a viable resolution for the embolism resulting from intravascular administration of PCL-containing fillers. Two different animal experiments were performed: (1) PCL-induced rat inferior epigastric arteries embolism, followed by gross observation, histological evaluation, and cytokines analysis from serum; and (2) PCL-induced rabbit auricular artery embolism, immediately treated with heparin and nitroglycerin. The ears were then evaluated by gross observation, Laser speckle imaging, in vivo imaging system (IVIS) imaging, and histological evaluation. Saline and hyaluronic acids (HA) were used as controls, hyaluronidase was used as a positive drug. In a rat model of inferior epigastric arteries embolism, both intravascular injection of HA and PCL resulted in flap necrosis, indicating that the filler-induced intravascular embolism can lead to serious complications. In a rabbit model of auricular artery embolism, the combination treatment of heparin and nitroglycerin resulted in a relative blood reperfusion recovery of 80% in the ischemic area of the PCL group on day 7 post-operation, which was comparable to that of the HA group treated with hyaluronidase. Histological analysis revealed that the administration of heparin and nitroglycerin significantly attenuated intravascular thrombosis formation and inflammatory cell aggregation. The combination of heparin and nitroglycerin effectively restores blood flow reperfusion in the intravascular embolization caused by PCL filler injection, alleviates local tissue edema and flap necrosis. These findings offer a novel approach for future clinical management of intravascular embolization with PCL-containing filler injection. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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.

Efficacy and Safety of Prehospital Diltiazem

Objective This study assesses the likelihood of clinical improvement and adverse events from EMS-administered diltiazem. Current prehospital protocols direct paramedics to administer diltiazem, a calcium channel blocker, to decrease the heart rate (HR) of symptomatic, hemodynamically stable patients with rapid atrial fibrillation. However, diltiazem can also cause systemic hypotension and bradycardia, which can precipitate end-organ injury. Methods To assess whether the rate control benefit of prehospital diltiazem outweighs the risk of adverse events, we conducted a retrospective chart review of all adult patients who received diltiazem from Maryland Advanced Life Support EMS clinicians between January 1, 2019, and March 31, 2022. Collected data included patient demographics, vital signs, diltiazem dose, transport times, administered medications, and procedures. The main outcomes were clinical improvement (HR <100 beats per minute or ≥20% decrease from the maximum HR) and adverse events (bradycardia or hypotension). Multivariable logistic regression was used for statistical analysis. Results During the study period, 2396 patients received prehospital diltiazem and 94% of these patients (n = 2254) were included in the study. Overall, 1414 (63.8%) patients improved clinically, 604 (27.3%) patients achieved rate control as defined by a HR of <100 beats per minute, and 78 patients (3.5%) experienced an adverse event. Patients over the age of 50 were less likely to clinically improve with diltiazem administration. Adverse events were more likely in patients with systolic blood pressures (SBP) less than 140 mmHg, patients with maximum HR of less than 120 beats per minute, and patients who received nitroglycerin. Conclusions Prehospital diltiazem is effective and safe for most patients. Adverse events are more likely in patients with baseline SBP less than 140 mmHg, HR less than 120 beats per minute, and concurrent nitroglycerin administration. Future opportunities for research include examining the relationship between adverse events and underlying etiology as well as investigating downstream outcomes.

Feasibility and Utility of Anatomical and Physiological Evaluation of Coronary Disease With Cardiac CT in Severe Aortic Stenosis (FUTURE-AS Registry): Rationale and Design

BackgroundCoronary artery disease (CAD) in patients with severe aortic stenosis (AS) is common and may be associated with worse outcomes. Computed tomography coronary angiography (CTCA) and fractional flow reserve derived from computed tomography (FFRCT) are tools for comprehensive coronary assessment. The utility and safety of CTCA and FFRCT in the work-up for transcatheter aortic valve replacement (TAVR) is not established, especially in an evolving landscape that involves younger TAVR patients. The FUTURE-AS Registry will assess the utility and safety of cardiac-optimized CTCA and FFRCT to evaluate CAD and guide referral for downstream invasive coronary angiography (ICA) in patients with severe AS being considered for TAVR. MethodsFUTURE-AS is an international, prospective, multicenter registry of patients with severe AS referred for TAVR being assessed for CAD with CTCA and FFRCT. The primary end point is the per-patient sensitivity and negative predictive value of CTCA and FFRCT for identifying anatomical and physiologically significant CAD compared to ICA and invasive FFR. The safety end point is the incidence of symptomatic hypotension or bradycardia requiring intervention following the administration of nitroglycerin or β-blocker medications. Feasibility end points include the incidence of noninterpretable CTCA scans and CTCA scans not adequate for FFR analysis. Other utility end points include specificity, positive predictive value, and accuracy of CTCA and FFRCT. Lastly, the potential of a CTCA and FFRCT guided strategy to defer pre-TAVR ICA will be assessed. ConclusionsFUTURE-AS will characterize the utility, safety, and feasibility of CTCA and FFRCT for coronary assessment pre-TAVR.

Unraveling the directional relationship of sleep and migraine-like pain.

Migraine and sleep disorders are common co-morbidities. Patients frequently link their sleep to migraine attacks suggesting a potential causal relationship between these conditions. However, whether migraine pain promotes or disrupts sleep or whether sleep disruption can increase the risk of migraine remains unknown. We assessed the potential impact of periorbital allodynia, a measure consistent with migraine-like pain, from multiple preclinical models on sleep quantity and quality. Additionally, we evaluated the possible consequences of sleep deprivation in promoting susceptibility to migraine-like pain. Following the implantation of electroencephalogram/electromyography electrodes to record sleep, mice were treated with either single or repeated systemic injections of nitroglycerin at the onset of their active phase (i.e. nocturnal awake period). Neither single nor repeated nitroglycerin affected the total sleep time, non-rapid eye movement sleep, rapid eye movement sleep, sleep depth or other measures of sleep architecture. To account for the possible disruptive effects of the surgical implantation of electroencephalogram/electromyography electrodes, we used immobility recordings as a non-invasive method for assessing sleep-wake behaviour. Neither single nor repeated nitroglycerin administration during either the mouse sleep (i.e. daylight) or active (i.e. night) periods influenced immobility-defined sleep time. Administration of an inflammatory mediator mixture onto the dura mater at either sleep or active phases also did not affect immobility-defined sleep time. Additionally, inhalational umbellulone-induced migraine-like pain in restraint-stressed primed mice did not alter immobility-defined sleep time. The possible influence of sleep disruption on susceptibility to migraine-like pain was evaluated by depriving female mice of sleep over 6 h with novel objects, a method that does not increase circulating stress hormones. Migraine-like pain was not observed following acute sleep deprivation. However, in sleep-deprived mice, subthreshold doses of systemic nitroglycerin or dural calcitonin gene-related peptide induced periorbital cutaneous allodynia consistent with migraine-like pain. Our data reveal that while migraine-like pain does not significantly disrupt sleep, sleep disruption increases vulnerability to migraine-like pain suggesting that a therapeutic strategy focused on improving sleep may diminish migraine attacks.

Hyperventilation testing in the diagnosis of vasospastic angina: A clinical review and meta-analysis.

Given the limited access to invasive vasospastic reactivity testing in Western Countries, there is a need to further develop alternative non-invasive diagnostic methods for vasospastic angina (VSA). Hyperventilation testing (HVT) is defined as a class IIa recommendation to diagnose VSA by the Japanese Society of Cardiology. In this systematic review and meta-analysis reported according to the PRISMA statement, we review the mechanisms, methods, modalities and diagnostic accuracy of non-invasive HVT for the diagnostic of VSA. A total of 106 articles published between 1980 and 2022 about VSA and HVT were included in the systematic review, among which 16 were included in the meta-analysis for diagnostic accuracy. Twelve electrocardiogram-HVT studies including 804 patients showed a pooled sensitivity of 54% (95% confidence intervals [CI]; 30%-76%) and a pooled specificity of 99% (95% CI; 88%-100%). Four transthoracic echocardiography-HVT studies including 197 patients revealed a pooled sensitivity of 90% (95% CI; 82%-94%) and a pooled specificity of 98% (95% CI; 86%-100%). Six myocardial perfusion imaging-HVT studies including 112 patients yielded a pooled sensitivity of 95% (95% CI; 63%-100%) and a pooled specificity of 78% (95% CI; 19%-98%). Non-invasive HVT resulted in a low rate of adverse events, ventricular arrhythmias being the most frequently reported, and were resolved with the administration of nitroglycerin. Non-invasive HVT offers a safe alternative with high diagnostic accuracy to diagnose VSA in patients with otherwise undiagnosed causes of chest pain.

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.

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.

Nitroglycerin to Ameliorate Coronary Artery Spasm During Focal Pulsed-Field Ablation for Atrial Fibrillation

BackgroundIn treating atrial fibrillation, pulsed-field ablation (PFA) has comparable efficacy to conventional thermal ablation, but with important safety advantages: no esophageal injury or pulmonary vein stenosis, and rare phrenic nerve injury. However, when PFA is delivered in proximity to coronary arteries using a pentaspline catheter, which generates a broad electrical field, severe vasospasm can be provoked. ObjectivesThe authors sought to study the vasospastic potential of a focal PFA catheter with a narrower electrical field and develop a preventive strategy with nitroglycerin. MethodsDuring atrial fibrillation ablation, a focal PFA catheter was used for cavotricuspid isthmus ablation. Angiography of the right coronary artery (some with fractional flow reserve measurement) was performed before, during, and after PFA. Beyond no nitroglycerin (n = 5), and a few testing strategies (n = 8), 2 primary nitroglycerin administration strategies were studied: 1) multiple boluses (3-2 mg every 2 min) into the right atrium (n = 10), and 2) a bolus (3 mg) into the right atrium with continuous peripheral intravenous infusion (1 mg/min; n = 10). ResultsWithout nitroglycerin, cavotricuspid isthmus ablation provoked moderate-severe vasospasm in 4 of 5 (80%) patients (fractional flow reserve 0.71 ± 0.08). With repetitive nitroglycerin boluses, severe spasm did not occur, and mild-moderate vasospasm occurred in only 2 of 10 (20%). Using the bolus + infusion strategy, severe and mild-moderate spasm occurred in 1 and 3 of 10 patients (aggregate 40%). No patient had ST-segment changes. ConclusionsAblation of the cavotricuspid isthmus using a focal PFA catheter routinely provokes right coronary vasospasm. Pretreatment with high doses of parenteral nitroglycerin prevents severe spasm.

Nitroglycerin use and adverse clinical outcomes in elderly patients with acute coronary syndrome

ObjectiveThe primary care for acute coronary syndrome (ACS) includes the administration of nitroglycerin (GTN). This study aimed to investigate the association between the use of GTN before percutaneous coronary intervention...

Successful recognition and management of life-threatening multivessel coronary artery vasospasm after conventional coronary artery bypass grafting.

Background: The occurrence of native coronary artery vasospasm after coronary artery bypass grafting (CABG) is a rare phenomenon with potentially catastrophic outcomes. The absence of a clear understanding of contributing factors and an undetermined occurrence rate underscores the importance of coronary angiography as the primary diagnostic tool for this condition. Case Presentation: We present the case of a 70-year-old Asian male with a 14-year history of diabetes mellitus, seven years of Giant Cell Arteritis (GCA), and Ischemic Heart Disease (IHD). The patient experienced severe native coronary artery vasospasm following conventional CABG, prompting intervention through coronary angiography. Management &amp; Results: The patient underwent coronary angiography, revealing multivessel coronary artery vasospasm. Intracoronary administration of nitroglycerin and diltiazem was initiated promptly. The swift identification and treatment of vasospasm were instrumental in preventing severe myocardial injury. Conclusion: Coronary artery vasospasm post-CABG poses a significant threat, emphasizing the need for early identification and intervention. The successful management presented in this case underscores the importance of timely recognition and the administration of vasodilators in mitigating potential myocardial damage. This report contributes to the growing understanding of this rare but critical complication, highlighting the necessity for vigilance in post-CABG patient care.

Abstract 18617: Concurrent Postural Orthostatic Tachycardia Syndrome (POTS) and Vasodepressor Syncope: A Unique Case in a Young Female

Introduction: Rare coexistence of postural orthostatic tachycardia syndrome and vasodepressor disorder in young patient's syncope poses intriguing diagnostic and treatment challenges. We report a case in a healthy young female. Case: A 28-year-old female without prior medical history presented with dizziness, palpitations, and syncope. A tilt table test revealed a significant increase in heart rate upon tilting to 70 degrees, indicative of postural orthostatic tachycardia syndrome (POTS). Later, administration of nitroglycerin resulted in syncope, consistent with vasodepressor disorder. Intravenous fluids alleviated symptoms. The patient was diagnosed with coexisting POTS and vasodepressor syndrome, treated with ivabradine for POTS, and compression stockings for vasodepressor disorder. Follow-up visits showed symptom improvement. Discussion: Autonomic disorders presenting as syncope pose diagnostic and therapeutic challenges due to their varied etiologies. Postural orthostatic tachycardia syndrome (POTS) involves excessive heart rate elevation upon upright posture, while vasodepressor syndrome manifests as orthostatic hypotension. Their coexistence is uncommon. Tilt table testing aids in distinguishing between the two. Treatment focuses on addressing specific pathophysiological mechanisms. Ivabradine and beta blockers target excessive tachycardia in POTS, while hydration and compression stockings mitigate orthostatic hypotension. Refractory cases may benefit from midodrine. A tailored approach is crucial in managing these complex autonomic disorders. Conclusion: Rare coexistence of two autonomic dysfunction syndromes emphasizes the need for tailored treatment. Individualized interventions, guided by underlying pathophysiology, are crucial. Larger studies are required for validation and to optimize diagnostic and therapeutic approaches in patients with coexisting POTS and vasodepressor syndrome.

Arterial stiffness of the aorta and iliofemoral artery and their responses to nitroglycerin administration in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits.

The role of hypercholesterolemia in arterial stiffness, which usually reflects the progression of atherosclerosis has not been fully investigated. To clarify the meaning of arterial stiffness in hypercholesterolemia, we evaluated arterial stiffness in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits by using new arterial stiffness indices of the aorta and common iliac to femoral artery. The new arterial stiffness indices of both arteries were determined by the application of the theory of cardio-ankle vascular index (CAVI) to the aorta (aBeta) and ilio-femoral artery (ifBeta). Furthermore, the responses of both indices to nitroglycerin (NTG) administration were compared between WHHHMI and normal rabbits. aBeta and ifBeta of WHHLMI and normal rabbits were measured under anesthesia. Pulse wave velocity in the whole aorta (aPWV) and ilio-femoral artery (ifPWV), blood pressure, and other parameters were measured before and after administration of NTG (50-120 μg/kg/min) every 1 for 5 min. Atherosclerotic lesions were observed in the aorta, but a little in the ilio-femoral artery in WHHLMI rabbits. Compared with normal rabbits, aBeta was significantly higher, but ifBeta was lower in WHHLMI rabbits. When NTG was administered, ifBeta decreased significantly in both groups; however, aBeta increased in normal rabbits, but remained unchanged in WHHIMI rabbits. These findings suggested that hereditary hypercholesterolemia in rabbits did not uniformly enhance arterial stiffness in elastic artery and muscular artery. The responses to NTG were also different between two arteries. The mechanism of these different responses needs further studies.

Flash pulmonary edema in the cardiac catheterization laboratory: a case report

Flash pulmonary edema is a potentially fatal condition that can suddenly deteriorate a patient's status in a variety of settings, including the catheterization laboratory. We describe a 51-year-old woman with a history of hypertension who was admitted for a second valve operation for degenerated aortic bioprosthesis. Before undergoing coronary angiography, she looked a little worried, she experienced respiratory distress and a significant increase in blood pressure in favor of acute flash pulmonary edema, which was immediately and successfully managed by respiratory support and administration of high-dose intravenous nitroglycerine and loop diuretic therapy. The present scenario highlights the significance of being aware of the warning signs of acute flash pulmonary edema to make a prompt diagnosis and initiate the appropriate treatment to prevent catastrophic consequences.

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.

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.

Aryl hydrocarbon receptors improve migraine-like pain behaviors in rats through the regulation of regulatory T cell/T-helper 17 cell-related homeostasis.

To investigate the effect of the aryl hydrocarbon receptor (AHR)/regulatory T cell (Treg)/T-helper 17 (Th17) cell pathway on the pathogenesis of migraine. Migraine is a disabling neurovascular disease that imposes an enormous burden on both individuals and society. The pathophysiological mechanisms of migraine remain controversial. Recent studies have suggested that immune dysfunction may be involved in the pathogenesis of migraine. The AHR, a receptor expressed on most immune cells, has been implicated in the occurrence of many autoimmune diseases; however, whether it is involved in the pathogenesis of migraine is unclear. A chronic migraine rat model was established through repeated intraperitoneal injection of nitroglycerin (NTG). The mechanical and thermal pain thresholds were assessed using von Frey filaments and radiant heat. Next, the protein expression levels of AHR in the trigeminal nucleus caudalis (TNC) region of chronic migraine (CM)-like rats were quantified and the changes in Treg/Th17-related transcription factors and inflammatory factors in the TNC were explored. To determine the role of AHR in CM, we examined the effects of the AHR agonist 2-(1'-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), and AHR antagonist CH-223191 on pain behavior, c-Fos, calcitonin gene-related peptide (CGRP), AHR, and Treg/Th17-related factor expression in CM-like rats. Repeated administration of NTG significantly enhanced nociceptive hypersensitivity and increased expression of c-Fos and CGRP in rats, while AHR was significantly decreased in the TNC. In addition, the expression of the transcription factor forkhead box protein P3 and the signal transducer and activator of transcription 5 decreased significantly. In contrast, the expression of the transcription factor retinoic acid receptor-related orphan receptor γ t and signal transducer and activator of transcription 3 were significantly increased. Moreover, the mRNA level of transforming growth factor beta-1 was decreased, while that of interleukin (IL)-10 and IL-22 was increased in the TNC. The AHR agonist ITE alleviated migraine-like pain behaviors in rats, activated the AHR signaling pathway, and improved the imbalance of Treg/Th17-related transcription factors and inflammatory factors. Conversely, the AHR antagonist CH-223191 did not alleviate migraine-like pain behaviors in rats; and even exacerbated them. The AHR participates in the development of CM by regulating Treg/Th17-related homeostasis. Therefore, treatments targeting the AHR/Treg/Th17 signaling pathway could be new effective interventions for CM treatment.