Administration Of Adenosine Research Articles

Coronary and Systemic Vasodilator Responsiveness of Patients Receiving Conventional Intermittent or Nocturnal Hemodialysis.

Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.

Safety of adenosine for pediatric tachyarrhythmia treatment in the emergency department: a multi-hospital 10-year cross-sectional study

BackgroundSupraventricular tachycardia is the most common dysrhythmia in children. Initial vagal maneuvers are successful less than half of the time. Adenosine, a potent AV nodal blocker with a short half-life, is recommended as first line pharmacotherapy. Minor side effects from adenosine are common, but report of serious side effects such as sustained ventricular tachycardia, torsades de pointes, syncope or hypotension are confined to small case series or studies greater than 20 years old. We aimed to specifically identify the incidence of serious side effects of adenosine in children in the emergency department.MethodsBetween 2002 and 2022, all children less than 18 years old who received adenosine for tachyarrhythmia treatment in two emergency departments were included. The electronic record was reviewed for demographic information, patient history, treatments given, and side effects or complications were observed. Electrocardiograms before, during and after adenosine administration were reviewed.Results77 patients met inclusion criteria. There were 74 patients with an initial rhythm of typical SVT. The other three patients included one with a junctional rhythm, one with atrial fibrillation, and one with an undetermined narrow complex tachycardia. 49 patients had cardiac rhythm monitoring during adenosine administration. 17 of these patients had three or more consecutive ventricular beats following adenosine, however no patients required treatment. No patients had syncope. One patient had brief hypotension after adenosine that normalized without intervention. Four patients were electrically cardioverted after adenosine, all for persistent dysrhythmias: two for persistent SVT with hypotension, one for atrial fibrillation and one for an undetermined rhythm. Twelve patients were placed on continuous antiarrhythmic medication for persistent SVT. Age, gender, prior SVT history, initial adenosine dose, and need for additional doses were not significant risk factors for a prolonged sinus pause or greater than two ventricular beats.ConclusionsAdenosine treatment in typical supraventricular tachycardia in pediatric patients is safe.

Use of coronary physiology to guide revascularization in clinical practice: results of the F(FR)2 registry

BackgroundDespite the recommendation of coronary physiology to guide revascularization in angiographically intermediate stenoses without established correlation to ischemia, its uptake in clinical practice is slow.AimsThis study aimed to analyze the use of coronary physiology in clinical practice.MethodsBased on a multicenter registry (Fractional Flow Reserve Fax Registry, F(FR)2, ClinicalTrials.gov identifier NCT03055910), clinical use, consequences, and complications of coronary physiology were systematically analyzed.ResultsF(FR)2 enrolled 2,000 patients with 3,378 intracoronary pressure measurements. Most measurements (96.8%) were performed in angiographically intermediate stenoses. Out of 3,238 lesions in which coronary physiology was used to guide revascularization, revascularization was deferred in 2,643 (78.2%) cases.Fractional flow reserve (FFR) was the most common pressure index used (87.6%), with hyperemia induced by an intracoronary bolus of adenosine in 2,556 lesions (86.4%) and intravenous adenosine used for 384 measurements (13.0%). The route of adenosine administration did not influence FFR results (change-in-estimate -3.1% for regression model predicting FFR from diameter stenosis). Agreement with the subsequent revascularization decision was 93.4% for intravenous and 95.0% for intracoronary adenosine (p = 0.261).Coronary artery occlusion caused by the pressure wire was reported in two cases (0.1%) and dissection in three cases (0.2%), which was fatal once (0.1%).ConclusionsIn clinical practice, intracoronary pressure measurements are mostly used to guide revascularization decisions in angiographically intermediate stenoses. Intracoronary and intravenous administration of adenosine seem equally suited. While the rate of serious complications of wire-based intracoronary pressure measurements in clinical practice seems to be low, it is not negligible.Graphical abstract

Extracellular ATP- and adenosine-mediated purinergic signaling modulates inducible nitric oxide synthase (iNOS) gene expression, enzyme activity and nitric oxide production in common carp (Cyprinus carpio) head kidney macrophages

Inducible nitric oxide (NO) synthase (iNOS) is a key immune mediator for production of inflammatory mediator NO from l-arginine. Tight regulation of iNOS expression and enzyme activity is critical for proper NO productions under inflammation and infection conditions. However, the regulatory mechanism for iNOS expression and enzyme activity in fish remains largely unknown. Here, we show that extracellular ATP treatment significantly up-regulates iNOS gene expression and enzyme activity, and consequently leads to enhanced NO production in Cyprinus carpio head kidney macrophages (HKMs). We further show that the extracellular ATP-induced iNOS enzyme activity and NO production can be attenuated by pharmacological inhibition of the ATP-gated P2X4 and P2X7 receptors with their respective specific antagonists, but enhanced by overexpression of P2X4 and P2X7 receptors in grass carp ovary cells. In contrast, adenosine administration significantly reduces iNOS gene expression, enzyme activity and NO production in carp HKMs, and these inhibitory effects can be reversed by pharmacological inhibition of adenosine receptors with the antagonist XAC. Furthermore, LPS- and poly(I:C)-induced iNOS gene expression, enzyme activity, and NO production are significantly attenuated by blockade of P2X4 and P2X7 receptors with their respective specific antagonists in carp HKMs, while overexpression of P2X and P2X7 receptors results in enhanced iNOS gene expression, enzyme activity and NO production in LPS- and poly(I:C)-treated grass carp ovary cells. Taken together, we firstly report an opposite role of extracellular ATP/adenosine-mediated purinergic signaling in modulating iNOS-NO system activity in fish.

Assessing the Potential of Adenosine and L-Theanine as Metabolic Suppressants for Improving Shipping of the New Zealand Scampi (Metanephrops challengeri)

Live crustaceans, especially lobsters, crabs, and shrimp, fetch premium prices in many international seafood markets, especially in parts of Asia. To access these market opportunities, live crustaceans frequently need to be transported over long distances, which can involve prolonged air exposure resulting in elevated stress and increased morbidity and mortality. Interventions which deliver metabolic suppression to live crustaceans during their transport have the potential to improve outcomes from live shipping. In this study, the administration of adenosine (Ado) and L-theanine (L-th) were assessed for metabolic suppression in the New Zealand scampi, Metanephrops challengeri, a deep sea lobster which is highly prized as seafood, and with excellent prospects for supply into premium live seafood markets. The administration to scampi of Ado and L-th in isolation or as a mixture (Ado/L-th), caused a significant decrease in heart rate (HR) with a lasting effect for the 4 hr experimental period. However, this depression of HR did not translate into a systemic downregulation of metabolism, as measured by the key metabolites, i.e., glycogen utilization and the accumulation of lactate and ammonia. The lack of systematic metabolic downregulation would preclude the potential use of Ado and L-th for commercial application in live shipping of crustaceans.

Validation Strategy for Pulmonary Vein Isolation in Patients With Paroxysmal Atrial Fibrillation in Long-Term Maintaining Sinus Rhythm: A Randomized Controlled Study.

Background: Data comparing the outcomes of loose versus rigorous validation strategies for pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (PAF) are limited. We aimed to prospectively assess the effectiveness of loose versus rigorous validation for PVI in patients with PAF with a maintained sinus rhythm. Methods: Patients (n = 117) with PAF were randomized to receive either loose validation (n = 59) or rigorous validation (n = 58) after PVI. The presence of dormant conduction in loose validation was assessed only by adenosine administration followed by isoproterenol infusion. The complete absence of pulmonary vein (PV) potentials in rigorous validation was confirmed by the combination of the Lasso catheter with isoproterenol plus adenosine. Dormant conduction, revealed by validation after PVI, was ablated until all reconnections were eliminated. Results: The procedure time in the rigorous validation group was greater than that in the loose validation group (161.3 ± 52.7 min vs. 142.5 ± 37.6 min, p=0.03, respectively). After successful PVI, the detection of dormant PV reconnections in the rigorous validation group was significantly greater than that in the loose validation group (69.0% vs. 37.3%, p=0.001). However, after reisolation of the sites of dormant PV conduction, the postablation recurrence rates in 1.3 years were similar between the groups (79.2% vs. 83.6%, p=0.67). Conclusion: Rigorous validation can reveal dormant conduction in more than two-thirds of patients with PAF undergoing PVI. However, rigorous validation and additional ablation of the resulting connections do not improve long-term outcomes when a protocol that includes electrophysiological confirmation and pharmacological validation is used.

Impact of Mitral Regurgitation on the Hyperemic Induction by Intravenous Administration of Adenosine

Impact of Mitral Regurgitation on the Hyperemic Induction by Intravenous Administration of Adenosine

Atrial Reentry Tachycardia: Mechanisms and Diagnosis

Atrial tachycardia (AT) is a group of arrhythmias that differ in electrophysiological mechanisms and clinical course. There are three main forms of AT: focal AT, macroreentries, and localized reentries also known as “microreentries”. Macroreentries, as a rule, occur in the presence of fibrous changes in the myocardium, for example, in “atrial” cardiomyopathy or as a result of catheter or surgical interventions in the atria. Focal AT can also occur in the absence of structural pathology of the heart.&#x0D; The aim. To analyze modern ideas about electrophysiological mechanisms and diagnosis of atrial reentry tachycardia.&#x0D; In our research we used data from the literature as well as findings of our own previous studies. The work analyzed global data on the distribution of various types of AT. The data of electrocardiographic (ECG) diagnosis, electrophysiological methods of diagnosis and pharmacological tests were also analyzed to determine the mechanism of occurrence and course of AT. The main ECG differences of different types and localizations of AT were determined. The diagnostic value of various stimulation protocols in the differential diagnosis of focal and macro-reentrant AT was also analyzed.&#x0D; Conclusions. Atrial tachycardias with a reentrant mechanism are common in the general population. Differential diagnosis with other types of tachycardia is carried out on the basis of ECG data, the response to adenosine administration, the nature of the response during entrainment, and endocardial, particularly electroanatomical, mapping.

Non-hyperaemic coronary flow velocity acceleration indices correlate with hyperaemic microvascular resistance in patients with INOCA

Abstract Background Coronary microvascular dysfunction (CMD) is associated with an overall worse prognosis. While the diagnosis and endo-typing of CMD currently rely on hyperaemic physiological indices, the search for accurate non-hyperaemic techniques continues. Flow velocity acceleration pattern is mechanistically associated with changes in shear stress, endothelial function, arterial stiffness and pressure in pulsatile flow systems (1-3). Purpose We aim to interrogate whether resting flow velocity acceleration indices correlate with hyperaemic microvascular resistance (HMR) in patients with Ischemia and no obstructive coronary artery disease (INOCA). Methods In 21 Patients with INOCA (all of whom had presented with typical angina pectoris, had no significant epicardial stenoses but positive myocardial perfusion scan test for ischemia) invasive physiological assessment was performed by means of intracoronary Doppler. Hyperaemia was induced with intracoronary adenosine administration. Coronary flow reserve (CFR) and HMR were calculated per their definitions. Flow velocity acceleration indices were derived from the first derivative of the averaged resting flow velocity waveforms with respect to time. We have defined 6 wave peaks of interest in all patients (peak diastolic acceleration (initial prominent peak with ventricular relaxation, referred as A), early diastolic deceleration (B), early re-acceleration wave (C), peak presystolic deceleration (seen just before initial systolic acceleration peak, J), initial systolic acceleration peak (X) and pre-diastolic deceleration nadir (Z)) and calculated the ratios between them as well as adjusted them with respect to resting mean flow velocity (Figure 1). Results The mean age was 59 ± 8 years and the majority of the study group was female (%81). Cardiovascular risk factors were common amongst the study group.All patients had CFR &amp;lt; 2.5. Mean CFR and HMR were 2.05 ± 0.32 and 2.20 ± 0.60 mmHg.cm.sec-1 respectively. Raw C peak magnitude was significantly correlated with APVh (rho:-0.457 p:0.037) and HMR (rho:0.612 p:0.004). Adjusting the C magnitudes with APVb at patient level yielded better correlations (APVh rho:-0.496 p:0.022 ; HMR:0.642 p:0.002). The ratio between diastolic reacceleration peak (C) and presystolic peak deceleration (J), C/J , adjusted with the APVb ((C/J)/APVb) showed the most pronounced correlation with HMR (rho: 0.758 p &amp;lt; 0.001) (unadjusted C/J – HMR rho: 0.718 p&amp;lt;0.001)(Figure 2). Conclusion(s) Acceleration characteristics of resting coronary flow velocity correlate with hyperaemic microvascular resistance indicating structurally impaired coronary microcirculation, hence their utilisation may aid developing non-hyperaemic physiological markers for coronary microvascular dysfunction in patients with INOCA.Derived Acceleration WaveformsCorrelations between HMR and C/J Ratio

The diagnostic and therapeutic challenge of atrial flutter in children: a case report

BackgroundPalpitations represent a common cause for consultation in the pediatric Emergency Department (ED). Unlike adults, palpitations in children are less frequently dependent from the heart, recognizing other causes.Case presentationA 11-year-old male came to our pediatric ED for epigastric pain, vomiting and palpitations. During the previous 6 month the patient was affected by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus). Electrocardiogram (ECG) revealed supraventricular tachycardia. Therefore, adenosine was administered unsuccessfully. The administration of adenosine, however, allowed us to make diagnosis of atypical atrial flutter. Multiple attempts at both electrical cardioversion, transesophageal atrial overdrive, and drug monotherapy were unsuccessful in our patient. Consequently, a triple therapy with amiodarone, flecainide, and beta-blocker was gradually designed to control the arrhythmic pattern with the restoration of a left upper atrial rhythm. There was not any evidence of sinus rhythm in the patient clinical history.ConclusionsThe present study underlines the rarity of this type of dysrhythmia in childhood and the difficulties in diagnosis and management, above all in a patient who has never showed sinus rhythm. Raising awareness of all available treatment options is essential for a better management of dysrhythmia in children

Keeping It "Current": A Review of Treatment Options for the Management of Supraventricular Tachycardia.

To review treatment options and updates that exist for the management of paroxysmal supraventricular tachycardia (PSVT). A literature search of PubMed was performed including articles from 1974 to June 2023 using the terms: arrhythmias, adenosine, verapamil, diltiazem, esmolol, propranolol, metoprolol, beta-blockers, amiodarone, PSVT, synchronized cardioversion, methylxanthines, dipyridamole, pediatrics, heart transplant, and pregnancy. Primary literature and guidelines were reviewed. Studies were considered if they were available in English and conducted in humans. PSVT is a subset of supraventricular tachycardia (SVT) that presents as a rapid, regular tachycardia with an abrupt onset and termination. Due to frequent emergency department (ED) visits annually with symptoms of PSVT, appropriate and efficient management of these patients is vital. This review provides an overview of the pathophysiology of PSVT, while also describing the literature behind nonpharmacologic and pharmacologic management of PSVT. This review describes new literature regarding the improved success of the modified Valsalva maneuver as a nonpharmacologic therapy in PSVT. In addition, it describes a new technique in administration of adenosine that has improved outcomes, defines dose adjustments needed for drug interactions with adenosine, compares the utilization of nondihydropyridine calcium channel blockers with adenosine, and provides management recommendations for patients in special populations. With high annual rates of ED visits for SVT, providers should be aware of the data behind management and modifications of therapy based on patient-specific factors (ie, patient preference, pharmacokinetics/pharmacodynamics, drug interactions, and special populations).

High-Power Short-Duration Lesion Index-Guided Posterior Wall Isolation beyond Pulmonary Vein Isolation for Persistent Atrial Fibrillation.

Background: High-power short-duration (HPSD) radiofrequency (RF) ablation has been adopted to improve atrial fibrillation (AF) ablation. Although the role of HPSD is well-established in pulmonary vein isolation (PVI), fewer data have assessed the impact of HPSD when addressing extra-pulmonary veins (PVs) targets. Therefore, this study aims to determine the safety, effectiveness, and acute outcomes of HPSD lesion index (LSI)-guided posterior wall isolation (PWI) in addition to PVI as an initial strategy in persistent atrial fibrillation (Pe-AF). Methods: Consecutive patients who underwent ablation of Pe-AF in our center between August 2021 and January 2022 were retrospectively enrolled. All patients' ablation strategy was PVI plus PWI using HPSD LSI-guided isolation. RF parameters included 50 W targeting LSI values of ≥5 on the anterior part of the PVs and anterior roofline and ≥4 for the posterior PVs aspect, bottom line, and within the posterior wall (PW). We compared the LSI values with and without acute conduction gaps after the initial first-pass PWI. Left atrial mapping was performed with the EnSite X mapping system and a high-density multipolar Grid-shaped mapping catheter. We compared the procedural characteristics using HPSD (n = 35) vs. a control group (n = 46). Results: Thirty-five consecutive patients were included in the study. PWI on top of PVI was achieved in all cases in the HPSD group. First-pass PVI was achieved in 93.3% of PVs (n = 126/135). First-pass roofline block was obtained in most patients (n = 31, 88.5%), while first-pass block of the bottom line was only achieved in 51.4% (n = 18). There were no significant differences compared to the control group; first-pass PVI was achieved in 94.9% of PVs (n = 169/178), first-pass roofline block in 89.1%, and bottom-line in 45.6% of patients. To achieve complete PWI with HPSD, scattered RF applications within the PW were necessary. No electrical reconnection of the PW was found after adenosine administration and the waiting period. The procedure and RF times were significantly shorter in the HPSD group compared to the control group, with values of 116.2 ± 10.9 vs. 144.5 ± 11.3 min, and 19.8 ± 3.6 vs. 26.3 ± 6.4 min, respectively, p < 0.001. Fluoroscopy time was comparable between both groups. No procedural complications were observed. At the 12-month follow-up, 71.4% of patients remained free from AF, with no differences between the groups. Conclusions: HPSD LSI-guided PWI on top of PVI seems effective and safe. Compared to a control group, HPSD is associated with similar rates of first-pass PWI and PVI but with a shorter procedural and RF time.

Transdermal administration of adenosine using microplasma and the examination of the effect of microplasma on stratum corneum using infrared spectroscopy

The strong barrier established by stratum corneum serves a protective purpose. It also prevents pharmacological compounds from being delivered via the epidermal layer. Microplasma discharge was used to overcome the barrier of epidermal layer to permeate adenosine. Depth of the microplasma effect into the stratum corneum layer was evaluated using tape striping method and attenuated total reflectance-Fourier transform IR spectroscopy (ATR-FTIR). Microplasma treatment caused increased permeability of stratum corneum lipids to a depth of several micrometers. The possible interaction between microplasma and stratum corneum lipids was studied on ceramide C4 by ATR-FTIR. Microplasma particles dominantly interacted with ceramide C4 at the bond between the NH and C=O causing possible dissociation and weakening of hydrogen bonding between molecules.

Myocardial Blood Flow Determination From Contrast-Free Magnetic Resonance Imaging Quantification of Coronary Sinus Flow.

Determination of myocardial blood flow (MBF) with MRI is usually performed with dynamic contrast enhanced imaging (MBFDCE ). MBF can also be determined from coronary sinus blood flow (MBFCS ), which has the advantage of being a noncontrast technique. However, comparative studies of MBFDCE and MBFCS in large cohorts are lacking. To compare MBFCS and MBFDCE in a large cohort. Prospective, sequence-comparison study. 147 patients with type 2 diabetes mellitus (age: 56+/-12 years; 106 male; diabetes duration: 12.9+/-8.1 years), and 25 age-matched controls. 1.5 Tesla scanner. Saturation recovery sequence for MBFDCE vs. phase-contrast gradient-echo pulse sequence (free-breathing) for MBFCS . MBFDCE and MBFCS were determined at rest and during coronary dilatation achieved by administration of adenosine at 140 μg/kg/min. Myocardial perfusion reserve (MPR) was calculated as the stress/rest ratio of MBF values. Coronary sinus flow was determined twice in the same imaging session for repeatability assessment. Agreement between MBFDCE and MBFCS was assessed with Bland and Altman's technique. Repeatability was determined from single-rater random intraclass and repeatability coefficients. Rest and stress flows, including both MBFDCE and MBFCS values, ranged from 33 to 146 mL/min/100 g and 92 to 501 mL/min/100 g, respectively. Intraclass and repeatability coefficients for MBFCS were 0.95 (CI 0.90; 0.95) and 5 mL/min/100 g. In Bland-Altman analysis, mean bias at rest was -1.1 mL/min/100 g (CI -3.1; 0.9) with limits of agreement of -27 and 24.8 mL/min/100 g. Mean bias at stress was 6.3 mL/min/100 g (CI -1.1; 14.1) with limits of agreement of -86.9 and 99.9. Mean bias of MPR was 0.11 (CI: -0.02; 0.23) with limits of agreement of -1.43 and 1.64. MBF may be determined from coronary sinus blood flow, with acceptable bias, but relatively large limits of agreement, against the reference of MBFDCE . 1 TECHNICAL EFFICACY STAGE: 2.

Resting Full-Cycle Ratio versus Fractional Flow Reserve: A SWEDEHEART-Registry-Based Comparison of Two Physiological Indexes for Assessing Coronary Stenosis Severity.

The adenosine-requiring physiological index fractional flow reserve (FFR) is the gold-standard method for determining the significance of intermediate lesions, while the resting full-cycle ratio (RFR) is a novel nonhyperaemic index without the need for adenosine administration. The aim of this study was to investigate the degree of concordance between RFR and FFR in indicating the need for revascularisation in patients with intermediate coronary lesions. This was a retrospective, registry-based study utilising data from the SWEDEHEART registry. Patients treated at Ryhov County Hospital in Jönköping, Sweden, between the 1st of January 2020 and the 30th of September 2021, were included. The degree of correlation and concordance between RFR and FFR was determined, both when used with a single cut-off (significant stenosis if RFR ≤0.89) and with a hybrid approach (significant stenosis if RFR ≤0.85, not significant if RFR ≥0.94, and FFR measurement when RFR was in the grey zone 0.86-0.93). The study population consisted of 143 patients with 200 lesions. The overall correlation between FFR and RFR was significant (r = 0.715, R2 = 0.511, p ≤ 0.01). A strong correlation was seen for lesions in the left anterior descending artery (LAD) and the left circumflex artery (LCX) (r = 0.748 and 0.742, respectively, both p ≤ 0.01), while the correlation in the right coronary artery (RCA) was moderate (r = 0.524, p ≤ 0.01). The overall concordance between FFR and RFR using a single cut-off was 79.0%. With a hybrid cut-off approach, the degree of concordance was 91%, with no need of adenosine in 50.5% of the lesions. In conclusion, there was a strong correlation and a high degree of concordance between FFR and RFR in determining the significance of a stenosis. The use of a hybrid approach could improve the identification of physiologically significant stenoses while minimising the use of adenosine.

Quantification of myocardial blood flow using stress cardiac magnetic resonance for the detection of coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): GE Healthcare. Background Myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD); however, evaluation of its diagnostic performance has primarily been limited to single-center studies. AQUA-MBF (Assessment of QUAntitative MBF using stress CMR) is an international study with the goal of assessing the diagnostic performance of stress MBF for the detection of CAD. In this study, we aim to determine how stress MBF assessment compared against visual analysis (VA) of stress CMR images for the detection of CAD. Methods. 144 individuals (89 (62%) men, age 62±16 years, 97 (68%) hypertension, 54 (38%) diabetes, 92 (64%) hyperlipidemia) from 9 centers who underwent dual sequence stress CMR (1.5T or 3.0T GE Healthcare) and also had either a coronary computed tomography angiography (CTA, n=31), invasive coronary angiogram (ICA, n=95), or low pre-test probability for CAD (n=18) were included. CAD was defined as the presence of: (1) a stenosis ≥50% in the left main coronary artery or ≥70% in the 1 major vessel based on ICA or CTA or (2) an invasive fractional flow reserve (FFR) ≤ 0.8. Absence of obstructive coronary disease (NOCAD) was defined as a no history of myocardial infarction and stenosis &amp;lt;50% by ICA or CTA, 50–70% stenosis with FFR&amp;gt;0.8, or a young individual with no cardiac risk factors. Myocardial perfusion imaging was performed during first pass perfusion of a gadolinium-based contrast agent following the administration of adenosine or regadenoson with a low-resolution image acquired to assess the arterial input function and 2–3 short axis slices acquired to assess myocardial perfusion. VA was performed by 2 experienced cardiologists who assigned a grade of 1–5 based on the probability a study was abnormal. Stress MBF values were determined for each of the 16 myocardial segments using Fermi deconvolution (CircleCVI). The global stress MBF was calculated as the average value of two segments with the lowest values from each of the three coronary artery territories. Unpaired t-test was used to compare stress MBF values between CAD vs NOCAD. Receiver-operating characteristics curves were used to determine diagnostic performance. Results. 60 patients had CAD (20: 1-vessel, 26: 2-vessel, and 14: 3-vessel) (Figure 1A) while 84 had NOCAD (Figure 1B). The global stress MBF in CAD was lower than in NOCAD (1.63±0.52ml/g/min vs 2.41±0.68ml/g/min, p&amp;lt;0.0001) (Figure 2A). Stress MBF had a higher AUC than VA (reader 1 – 0.83 vs 0.73, p = 0.07: reader 2–0.83 vs 0.71, p = 0.02). The optimal stress MBF cut-off value for detecting CAD was 2.05ml/g/min (Figure 2B). Conclusions. In this multicenter study, we show that global stress MBF reported as a single value can identify patients with CAD at least as accurately as VA performed by physicians experienced in the interpretation of stress CMR images.

The Single-Syringe Versus the Double-Syringe Techniques of Adenosine Administration for Supraventricular Tachycardia: A Systematic Review and Meta-Analysis.

The intravenous double-syringe technique (DST) of adenosine administration is the first-line treatment for stable supraventricular tachycardia (SVT). Alternatively, the single-syringe technique (SST) was recently found to be potentially beneficial in several studies. This study aimed to perform a meta-analysis of the SST versus the DST of adenosine administration for the treatment of SVT. We assessed EMBASE, PubMed, Cochrane, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the DST to the SST of adenosine administration in patients with SVT. Outcomes included termination rate, termination rate at first dose, total administered dose, adverse effects, and discharge rate. We included four studies (three RCTs and one NRSI) with a total of 178 patients, of whom 99 underwent the SST of adenosine administration. No significant difference was found between treatment groups regarding termination rate, termination rate restricted to RCTs, total administered dose, and discharge rate. Termination rate at first dose (odds ratio 2.87; confidence interval 1.11-7.41; p = 0.03; I2 = 0%) was significantly increased in patients who received the SST. Major adverse effects were observed in only one study. The SST is probably as safe as the DST and at least as effective for SVT termination, SVT termination at first dose, and discharge rate from the emergency department. However, definitive superiority of one technique is not feasible given the limited sample size. PROSPERO identifier nº CRD42022345125.

PO-05-155 A CASE OF ALCOHOL LEADING TO ISOLATION IN THE ELECTROPHYSIOLOGY LABORATORY

Ligament of Marshall alcohol ablation is a treatment for refractory atrial fibrillation and left atrial flutter. Left atrial appendage (LAA) isolation resulting from LOM ablation has not been described. To describe a case of LOM alcohol ablation which resulted in left atrial appendage isolation and dissociation of a left atrial appendage reentrant atrial flutter from the atria. A middle aged man with a history of atrial fibrillation and multiple left atrial flutters was referred for repeat ablation after multiple prior unsuccessful ablations. He previously underwent surgical MAZE and 3 endocardial ablations including an anterior mitral line and endocardial and epicardial mitral isthmus line without achieving bidirectional block. He had recurrent, symptomatic atrial flutter despite therapy with dofetilide and metoprolol. The patient presented in an atypical flutter. The ligament of Marshall was cannulated and alcohol was sequentially injected for a total of 3.8 mL. After the first alcohol injection, the tachycardia abruptly terminated on the coronary sinus (CS) catheter and sinus rhythm resumed (Figure, blue arrows), though the surface ECG showed ongoing small atrial flutter waves (Figure, red arrows). Subsequent left atrial mapping confirmed that the left atrial appendage (LAA) was isolated from the remaining left and right atrium and remained in atrial flutter (Figure C). Overdrive pacing from a multipolar catheter in the LAA demonstrated a post-pacing interval within 20 ms of the tachycardia-cycle length (Figure C). Adenosine administration resulted in AV block but no alteration in tachycardia cycle-length. These findings were highly suggestive of a reentrant mechanism. Because 3D mapping was limited by dissociated CS and LAA rhythms, manual activation mapping was performed with earliest activation at the anterior superior LAA. RF ablation at this site resulted in atrial flutter slowing and termination. In a patient with LAA flutter and prior anteroseptal and lateral linear endocardial ablation, LOM alcohol ablation may isolate the LAA. This should be recognized when counseling patients and planning procedures.

Enokitake Mushroom and Its Active Component, Adenosine, Which Restores Testosterone Production in Impaired and Fatigued Mouse Models

Several studies have reported the effects of the consumption of various mushroom species on the testes in animal experimental models. Mushrooms, including enokitake mushrooms (Flammulina velutipes), and vegetables contain adenosine may affect testosterone production. Here, we aimed to elucidate the effects of enokitake and its active component, adenosine, on testosterone production in primary cultures of testicular cells in vivo using mice models and in vitro. The administration of enokitake ethanolic extract increased testosterone production in the cisplatin-impaired mouse model. The direct effect of mushroom extracts on testicular cells was examined and liquid chromatography–mass spectrometry analysis confirmed that the mushroom- and vegetable-induced increase in testosterone production mainly involved adenosine. Additionally, the administration of enokitake extract or adenosine to wet floor fatigue model mice promoted testicular testosterone production and enhanced Leydig cell function through insulin-like peptide three level upregulation. Structurally related compounds, including cordycepin, showed lower bioactivity than adenosine. This study showed that the ingestion of adenosine-containing mushrooms and vegetables may effectively increase testicular testosterone production. We conclude that mushrooms with a relatively high adenosine content, such as enokitake, may be useful against aging and fatigue.

Adenosine receptor A1 enhanced mitochondrial biogenesis and exerted neuroprotection after cerebral ischemia through PGC-1α

Ischemic stroke is a common cause of morbidity and mortality worldwide. The current treatment fails to achieve satisfactory results, because interventional therapy as first-line treatment management has a strict time window. In recent years, a large number of studies have confirmed that adenosine, as an inhibitory neurotransmitter, has a protective effect on cerebral ischemic injury. Nevertheless, direct administration of adenosine has many side effects. Previous studies showed that adenosine exerted neuroprotective effects mainly through adenosine receptor A1 (A1 receptor). Therefore, further study on the mechanism of A 1 receptor induced neuroprotection may find new targets for stroke treament. Mitochondrial biogenesis (MB) is a therapeutic target for ischemic stroke, and the nuclear-encoded peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) is a major regulator of MB. However, the influence of A1 receptor on MB and PGC-1α is unclear. In this study, using the middle cerebral artery occlusion (MCAO) model of mice, we evaluated the temporal and spatial effects of A1 receptor after ischemic stroke and verified the neuroprotection of A1 receptor. Neurological scores were used to assess functional changes in mice. At the same time, we observed the effect of activating A1 receptor on MB and PGC-1α, and the effect of knockdown PGC-1α on A1 receptor induced MB in vitro. WB and immunofluorescence were used to detect relevant indicators of MB. In addition, we downregulated PGC-1α in vivo to observe the effects on A1 receptor induced MB and neuroprotection. The findings indicated that A1 receptor was increased and mainly expressed on neurons in the penumbra, further activated A1 receptor after stroke had neuroprotection. In vitro, activation of A1 promotes MB and increases the expression level of PGC-1α, while downregulation of PGC-1α partially reverses the effect of A1 receptor after OGD/R. Down regulation of PGC-1α in the penumbra neurons can reverse the effects of activation of A1 receptor on MB and neuroprotection. Taken together, these findings indicated that A1receptor promotes MB and improves neurological function after ischemic stroke via PGC-1α.