Doses Of Adenosine Research Articles

High dose escalation of intracoronary adenosine in the assessment of fractional flow reserve: A retrospective cohort study.

Maximal hyperaemia for fractional flow reserve (FFR) may not be achieved with the current recommended doses of intracoronary adenosine. Higher doses (up to 720 μg) have been reported to optimize hyperaemic stimuli in small dose-response studies. Real-world data from a large cohort of patients is needed to evaluate FFR results and the safety of high-dose escalation. This is a retrospective study aimed to evaluate the safety and frequency of FFR ≤0.8 after high-dose escalation of intracoronary adenosine. Data were extracted from the medical databases of two university hospitals. Increasing doses (100, 200, 400, 600, and 800 μg) of adenosine were administered as intracoronary boluses until FFR ≤0.8 was achieved or heart block developed. The percentage of FFR ≤0.8 after higher-dose escalation was compared with those at conventional doses, and the predictors for FFR ≤0.8 after higher doses were analysed. In the 1163 vessels of 878 patients, 402 vessels (34.6%) achieved FFR ≤0.8 at conventional doses and 623 vessels (53.6%) received high-dose escalation. An additional 84 vessels (13.5%) achieved FFR ≤0.8 after high-dose escalation. No major complications developed during high-dose escalation. Borderline FFR (0.81–0.85) at the conventional dose, stenosis >60%, and triple-vessel disease increased the likelihood of FFR ≤0.8 after high-dose escalation, but chronic kidney disease decreased it. For vessels of borderline FFR at conventional doses, 46% achieved FFR ≤0.8 after high-dose escalation. In conclusion, High-dose escalation of intracoronary adenosine increases the frequency of FFR ≤0.8 without major complications. It could be especially feasible for borderline FFR values near the 0.8 diagnostic threshold.

Oseltamivir-Associated Supraventricular Tachycardia in an Infant

Oseltamivir is a neuraminidase inhibitor that is labeled for prophylaxis and treatment of influenza. We describe a previously healthy 4-month-old infant who tested positive for influenza A and was started on oseltamivir. One hour after receiving his first dose of oseltamivir, the infant had a diaphoretic episode and appeared grey and clammy. The infant was subsequently seen by the primary care physician and referred for admission to the hospital. Approximately 40 minutes after the second dose of oseltamivir in the hospital, the infant's heart rate rose to greater than 300 bpm. An electrocardiogram was suggestive of supraventricular tachycardia. At the time of the event, the infant received 2 doses of adenosine, and oseltamivir was discontinued prior to transfer to a tertiary facility for a higher level of care.

Low-dose adenosine-induced transient asystole during intracranial aneurysm surgery.

Background: Few studies have evaluated the adenosine dose that induces cardiac arrest during intracranial aneurysm surgery. We present our experiences with adenosine-induced transient asystole (AiTA) during intracranial aneurysm surgery and dosage recommendations.Methods: We retrospectively reviewed the medical records of all patients who underwent intracranial aneurysm surgery between July 2016 and December 2018. Patients who experienced AiTA during intracranial aneurysm surgery were included in the study.Results: Our study included nine intracranial aneurysm surgeries performed in eight patients. Thirteen episodes of AiTA were reported. Five of these were performed to facilitate bleeding control due to intraoperative aneurysm rupture (IAR), and adenosine doses were 9 mg (0.20 mg/kg), 12 mg (0.25 mg/kg), 12 mg (0.26 mg/kg), 18 mg (0.34 mg/kg), and 18 mg (0.39 mg/kg), resulted in transient asystole for 12, 14, 9, 44, and 18 s, respectively. For episodes without IAR, adenosine doses ranging from 6 to 18 mg (0.11–0.39 mg/kg) caused asystole for 8–33 s. In five episodes without IAR, low-dose adenosine (lower than 0.2 mg/kg) was used and caused asystole ranging from 8 to 12 s. Postoperatively, two patients had elevated cardiac troponin T levels but normal electrocardiograms.Conclusion: AiTA can facilitate the clipping of intracranial aneurysms at low-risk of serious cardiac complications. An adenosine dose of 0.2–0.4 mg/kg is safe and effective in both IAR and non IAR situations. In non IAR cases, we propose that low-dose AiTA is an option to facilitate aneurysm clipping. A starting dose of 6 mg or 0.1–0.2 mg/kg can adequately induce brief asystole by softening the aneurysmal sac during clip application.

Advantages of Modified Stoppa Approach in Mangement of Acetabular Fractures

This study presents our experience of internal fixation of the acetabular fractures and pelvic fractures using a newly modified Stoppa approach, which provides closer visualization to the entire anterior column, quadrilateral surface and the pelvic brim portion of the posterior column, and permits stable internal fixation for the acetabular fracture patterns with main anterior displacement and the anterior and lateral parts of the pelvis. The present study was a prospective clinical study including 10 patients with acetabular fractures who were treated operatively using modified Stoppa approach . The classification of acetabular fractures described by Letournel and Judet. All operative data was recorded Patients were followed-up for 12 months after the operation. The maximum displacement of the bony fragment was measured in the unit of mm by using PACS, Marosis mview ver. 5.4 Our result shows the incidence of perioperative complication. Two patients developed DVT and two patients developed obturator nerve palsy. Our result shows the radiological outcomes of the included patients. The mean CT gap was 1.685 ±0.27mm. Eighty percent of the patients had anatomical Matta class. Our result shows the Merle D‟Aubigne-Postel score of the included patients. Eighty percent of the patients had excellent score. The incidence of MVO after PPCI may be lowered by the addition of manual TA (6,24). The results of the present study show that the additional intracoronary administration of a high dose of adenosine may further improve STR up to 70%. Future larger studies with clinical endpoints are warranted to confirm the benefit of intracoronary administration of a high dose of adenosine in addition to glycoprotein IIb/ IIIa antagonist administration and TA in the setting of PPCI or rescue PCI.

Splenic Switch-Off for Determining the Optimal Dosage for Adenosine Stress Cardiac MR in Terms of Stress Effectiveness and Patient Safety.

Adenosine stress MRI is well established for the evaluation of known and suspected coronary artery disease. However, a proportion of patients might be "under-stressed" using the standard adenosine dose. To compare three different adenosine dosages for stress MRI in terms of stress adequacy based on splenic switch-off (SSO) and limiting side effects. Prospective. In all, 100 patients were randomized in group 1 (33 pts), group 2 (34 pts), and group 3 (33 pts), receiving dosages of 140 μg/kg/min, 175 μg/kg/min, or 210 μg/kg/min, respectively. SSO was evaluated visually and quantitatively. Stress perfusion was performed using a 1.5T scanner in three short axes using a standard single-shot, saturation recovery gradient-echo sequence. Three blinded experienced operators evaluated SSO on stress and rest perfusion acquisitions in the three groups. The signal intensity of the spleen and myocardium and the presence of inducible ischemia and late gadolinium enhancement were assessed. T-test, analysis of variance (ANOVA), chi-squared test, and Pearson's correlation coefficient. SSO was present more frequently in patients receiving 175 μg/kg/min and 210 μg/kg/min (31/33 [94%] and 27/29 [93%], respectively) compared to those receiving the standard dose (19/33 [58%], P < 0.05). A positive stress result was noted in 3/33 (9%) patients receiving 140 μg/kg/min vs. 9/33 (27%) patients receiving 175 μg/kg/min and 10/31 (33%) patients receiving 210 μg/kg/min (P < 0.05 for all, P < 0.05 for group 1 vs. groups 2, 3). The relative decrease of splenic signal intensity at hyperemia vs. baseline was significantly lower in group 1 compared to groups 2 and 3 (-33% vs. -54%, -56%, respectively; P < 0.05). No adverse events during scanning were noted in groups 1 and 2, whereas in group 3 four examinations were stopped due to severe dyspnea (n = 2) and AV-blockage (n = 2). A dosage of 175 μg/kg/min adenosine results in a higher proportion of SSO, which may be an indirect marker of adequate coronary vasodilatation and simultaneously offers similar safety compared to the standard 140 μg/kg/min dosage. 1 TECHNICAL EFFICACY STAGE: 2 J. MAGN. RESON. IMAGING 2020;52:1732-1742.

Dissolving microneedle with high molecular weight hyaluronic acid to improve skin wrinkles, dermal density and elasticity.

Dissolving microneedle patches have been extensively studied in the field of cosmetics comparison with topical cosmetics focusing on the delivery of active ingredients. Nevertheless, the skin improvement effect of hyaluronic acid, which is mainly used as a backbone material for dissolving microneedle, was not analyzed. In this study, adenosine encapsulated high and low molecular weight hyaluronic acid dissolving microneedle patch (Ad-HMN and Ad-LMN) were evaluated with respect to skin wrinkling, dermal density, elasticity, and safety in a clinical test on the crow's feet area. Clinical efficacy and safety tests were performed for 12weeks on twenty three female subjects with wrinkles around their eyes. The Ad-HMN and Ad-LMN patch were applied once every 3days, in the evening, for 8weeks to the designated crow's feet area. Skin wrinkling, dermal density, and elasticity were measured by using PRIMOS® premium, Dermascan® C, Cutometer® MPA580, and Corneometer® CM 825, respectively. Both Ad-HMN and Ad-LMN groups showed statistically significant efficacy for almost all parameters. The Ad-HMN patch had better effect on the mean depth of biggest wrinkles, maximum depth of biggest wrinkles, dermal density, and skin elasticity than the Ad-LMN patch. No adverse effects were observed in either group during the test period. In the clinical efficacy test of four skin-improvement parameters, the Ad-HMN patch showed the better effect than the Ad-LMN patch with the similar adenosine dose.

Randomized trial of intracoronary adenosine as adjunctive therapy for prevention of the no-reflow phenomenon.

No-reflow phenomenon as a serious complication following percutaneous coronary intervention, deteriorates clinical outcomes. Intracoronary (IC) Adenosine, seems to be a way to deal with it. One hundred four consecutive patients with ST-segment elevation myocardial infarction were randomized into two groups. Each group consisted of 52 patients who managed with two bolus doses of IC Adenosine (Adenosine group) or two bolus doses of IC normal saline (placebo group) administered before and after stenting. Thrombolysis in myocardial infarction (TIMI) grade flow, ST-segment resolution (STR) and post-procedural clinical outcomes were used as endpoints. IC adenosine led to lower rates of no-reflow based on TIMI grade flow scaling (15.4% vs. 44.3%; P-value: 0.02). STR classified as complete, partial and no resolution was similar between two groups (P-value: 0.748). Also, post-interventional clinical outcomes, including arrhythmia, left ventricular ejection fraction, hospitalization time, and 30 days mortality were similar between Adenosine and placebo groups.

Supraventricular Tachycardia Treatment in the Pediatric Emergency Department: Evaluation of Adenosine Dose and Treatment Response

Supraventricular Tachycardia Treatment in the Pediatric Emergency Department: Evaluation of Adenosine Dose and Treatment Response

Adenosine-Induced Transient Asystole During Surgical Treatment of Basilar Artery Aneurysms

To evaluate the safety and efficacy of adenosine-induced transient asystole (AITA) during surgery for basilar artery aneurysms. All the patients with basilar artery aneurysms operated using AITA at our institute during two years period (August 2013-July 2015) were included in this study. Adenosine was used in 11 patients with 13 basilar artery aneurysms. Seven of these aneurysms were basilar bifurcation aneurysms, four were basilar-superior cerebellar artery junction aneurysms, and two were distal basilar trunk aneurysms. The indications for AITA were narrow corridor for placement of temporary clip in 11 aneurysms, intraop rupture in 1 aneurysm, and circumferential dissection of a large aneurysm in 1. The mean dose of adenosine used for inducing asystole was 19.4 mg (range: 15-30 mg) and the mean total dose of adenosine used was 40.6 mg (range: 18-90 mg). A mean of 2 (range: 1-5) AITAs were required during surgical treatment of these aneurysms. The mean duration of a systole was 27 s (range: 9-76 s). There were no complications related to AITA in these patients except for transient rebound hypertension in one patient. Check angiogram revealed complete obliteration of 11 aneurysms and small residual neck in 2 aneurysms. Modified Rankin Scale at three months of follow-up was 0 in seven patients, 1 in two patients, 4 in one patient, and 6 in one patient. AITA during surgical management of basilar artery aneurysms is a safe and effective technique and has an important role during surgery for these aneurysms.

Preclinical Validation of a Single-Scan Rest/Stress Imaging Technique for 13N-Ammonia Positron Emission Tomography Cardiac Perfusion Studies.

We previously proposed a technique for quantitative measurement of rest and stress absolute myocardial blood flow (MBF) using a 2-injection single-scan imaging session. Recently, we validated the method in a pig model for the long-lived radiotracer 18F-Flurpiridaz with adenosine as a pharmacological stressor. The aim of the present work is to validate our technique for 13NH3. Nine studies were performed in 6 pigs; 5 studies were done in the native state and 4 after infarction of the left anterior descending artery. Each study consisted of 3 dynamic scans: a 2-injection rest-rest single-scan acquisition (scan A), a 2-injection rest/stress single-scan acquisition (scan B), and a conventional 1-injection stress acquisition (scan C). Variable doses of adenosine combined with dobutamine were administered to induce a wide range of MBF. The 2-injection single-scan measurements were fitted with our nonstationary kinetic model (MGH2). In 4 studies, 13NH3 injections were paired with microsphere injections. MBF estimates obtained with our method were compared with those obtained with the standard method and with microspheres. We used a model-based method to generate separate rest and stress perfusion images. In the absence of stress (scan A), the MBF values estimated by MGH2 were nearly the same for the 2-radiotracer injections (mean difference: 0.067±0.070 mL·min-1·cc-1, limits of agreement: [-0.070 to 0.204] mL·min-1·cc-1), showing good repeatability. Bland-Altman analyses demonstrated very good agreement with the conventional method for both rest (mean difference: -0.034±0.035 mL·min-1·cc-1, limits of agreement: [-0.103 to 0.035] mL·min-1·cc-1) and stress (mean difference: 0.057±0.361 mL·min-1·cc-1, limits of agreement: [-0.651 to 0.765] mL·min-1·cc-1) MBF measurements. Positron emission tomography and microsphere MBF measurements correlated closely. Very good quality perfusion images were obtained. This study provides in vivo validation of our single-scan rest-stress method for 13NH3 measurements. The 13NH3 rest/stress myocardial perfusion imaging procedure can be compressed into a single positron emission tomography scan session lasting less than 15 minutes.

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine With Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment.

Intravenous infusion of adenosine is considered standard practice for fractional flow reserve (FFR) assessment but is associated with adverse side-effects and is time-consuming. Intracoronary bolus injection of adenosine is better tolerated by patients, cheaper, and less time-consuming. However, current literature remains fragmented and modestly sized regarding the equivalence of intracoronary versus intravenous adenosine. We aim to investigate the relationship between intracoronary adenosine and intravenous adenosine to determine FFR. We performed a lesion-level meta-analysis to compare intracoronary adenosine with intravenous adenosine (140 µg/kg per minute) for FFR assessment. The search was conducted in accordance to the Preferred Reporting for Systematic Reviews and Meta-Analysis statement. Lesion-level data were obtained by contacting the respective authors or by digitization of scatterplots using custom-made software. Intracoronary adenosine dose was defined as; low: <40 µg, intermediate: 40 to 99 µg, and high: ≥100 µg. We collected 1972 FFR measurements (1413 lesions) comparing intracoronary with intravenous adenosine from 16 studies. There was a strong correlation (correlation coefficient =0.915; P<0.001) between intracoronary-FFR and intravenous-FFR. Mean FFR was 0.81±0.11 for intracoronary adenosine and 0.81±0.11 for intravenous adenosine (P<0.001). We documented a nonclinically relevant mean difference of 0.006 (limits of agreement: -0.066 to 0.078) between the methods. When stratified by the intracoronary adenosine dose, mean differences between intracoronary and intravenous-FFR amounted to 0.004, 0.011, or 0.000 FFR units for low-dose, intermediate-dose, and high-dose intracoronary adenosine, respectively. The present study documents clinically irrelevant differences in FFR values obtained with intracoronary versus intravenous adenosine. Intracoronary adenosine hence confers a practical and patient-friendly alternative for intravenous adenosine for FFR assessment.

Delayed adenosine therapy is associated with the refractory supraventricular tachycardia in children

ObjectivesTo study the association of time intervals on adenosine therapy with the occurrence of refractory supraventricular tachycardia (SVT) in children. MethodsWe reviewed 334 episodes of presumed SVT requiring adenosine in children (<18 years) who visited 4 academic hospital emergency departments (EDs) from July 2013 through June 2017. Refractory SVT was defined as an SVT episode persisting after 2 doses of adenosine. Clinical and electrocardiographic findings, and symptom-to-adenosine (symptom-to-ED plus ED-to-adenosine) time of refractory and responsive SVT episodes were compared. Multivariable logistic regression was performed to identify factors associated with the occurrence of refractory SVT. ResultsOf 211 SVT episodes, 42 episodes of refractory SVT (19.9%) were noted (overall sinus conversion rate, 79.6%). The refractory episodes were associated with a higher frequency of known structural heart diseases (9.5% vs. 1.8%; P = 0.030) and a longer median ED-to-adenosine time (15.5 vs. 11.0 min; P = 0.018). The association of the ED-to-adenosine time with refractory SVT remained significant after adjustment (for increment of 1 min; aOR, 1.02; 95% CI, 1.007–1.04). ConclusionsDelayed adenosine therapy is associated with the occurrence of refractory SVT in children, supporting the need for prompt adenosine therapy.

Exogenous adenosine facilitates neuroprotection and functional recovery following cerebral ischemia in rats

Introduction & ObjectiveCerebral ischemia causes physiological and biochemical cellular changes that ultimately result in structural and functional damage to hippocampal neurons. Ischemia also raises endogenous adenosine release that in turn has neuroprotective effects. The purpose of this study was to evaluate the effect of exogenous adenosine on mitigating neuronal lesions to the CA1 region of hippocampus and A2A protein expression following cerebral I/R in rats. MethodsMale Wistar rats were randomly assigned to three experimental groups (sham, ischemia + control, and ischemia + adenosine). A daily dose of adenosine (0.1 mg/ml/kg, i.p.) was administered starting 24 h post-ischemia for 7 days. Ischemia was induced by occlusion of both common carotid arteries for 45 min. Cresyl violet and Hematoxylin Eosin staining were used to assess lesion extent and location. To investigate the expression and protein levels, immunohistochemistry and enzyme-linked immunosorbent assay method was used. ResultsThe cerebral ischemia caused neuronal loss in the CA1 region and reduced sensorimotor functions in lesion animals. Injection of adenosine significantly diminished cell death and improved sensorimotor functional recovery. Moreover, the expression and concentration of A2A protein was significantly greater in the adenosine group compared to the ischemia group. ConclusionThis study showed that the administration of exogenous adenosine promotes protection against cell death and supports functional recovery following ischemic injury.

Adenosine stress CMR perfusion imaging of the temporal evolution of perfusion defects in a porcine model of progressive obstructive coronary artery occlusion

Adenosine stress CMR perfusion imaging can quantify absolute perfusion and myocardial perfusion reserve (MPR) in coronary artery disease (CAD) with higher spatial resolution than positron emission tomography, the only clinically available technique for quantitative myocardial perfusion imaging. While porcine models of CAD are excellent for studying perfusion abnormalities in chronic CAD, to date there are a limited number of studies that use quantitative perfusion for evaluation. Therefore, we developed an adenosine stress CMR protocol to evaluate the temporal evolution of perfusion defects in a porcine model of progressive obstructive CAD. 10 Yucatan minipigs underwent placement of an ameroid occluder around the left circumflex artery (LCX) to induce a progressive chronic coronary obstruction. Four animals underwent a hemodynamic dose range experiment to determine the adenosine dose inducing maximal hyperemia. Each animal had a CMR examination, including stress/rest spiral quantitative perfusion imaging at baseline and 1, 3, and 6weeks. Late gadolinium enhancement images determined the presence of myocardial infarction, if any existed. Pixelwise quantitative perfusion maps were generated using Fermi deconvolution. The results were statistically analyzed with a repeated mixed measures model to block for physiological variation between the animals. Five animals developed myocardial infarction by 3weeks, while three developed ischemia without an infarction. The perfusion defects were located in the inferolateral myocardium in the perfusion territory of the LCX. Stress perfusion values were higher in remote segments than both the infarcted and ischemic segments (p<0.01). MPR values were significantly greater in the remote segments than infarcted and ischemic segments (p<0.01). While the MPR decreased in all segments, the MPR recovered by the sixth week in the remote regions. We developed a model of progressive CAD and evaluated the temporal evolution of the development of quantitative perfusion defects. This model will serve as a platform for understanding the development of perfusion abnormalities in chronic occlusive CAD.

Cardioprotection of PLGA/gelatine cardiac patches functionalised with adenosine in a large animal model of ischaemia and reperfusion injury: A feasibility study.

The protection from ischaemia‐reperfusion‐associated myocardial infarction worsening remains a big challenge. We produced a bioartificial 3D cardiac patch with cardioinductive properties on stem cells. Its multilayer structure was functionalised with clinically relevant doses of adenosine. We report here the first study on the potential of these cardiac patches in the controlled delivery of adenosine into the in vivo ischaemic‐reperfused pig heart. A Fourier transform infrared chemical imaging approach allowed us to perform a characterisation, complementary to the histological and biochemical analyses on myocardial samples after in vivo patch implantation, increasing the number of investigations and results on the restricted number of pigs (n = 4) employed in this feasibility step. In vitro tests suggested that adenosine was completely released by a functionalised patch, a data that was confirmed in vivo after 24 hr from patch implantation. Moreover, the adenosine‐loaded patch enabled a targeted delivery of the drug to the ischaemic‐reperfused area of the heart, as highlighted by the activation of the pro‐survival signalling reperfusion injury salvage kinases pathway. At 3 months, though limited to one animal, the used methods provided a picture of a tissue in dynamic conditions, associated to the biosynthesis of new collagen and to a non‐fibrotic outcome of the healing process underway. The synergistic effect between the functionalised 3D cardiac patch and adenosine cardioprotection might represent a promising innovation in the treatment of reperfusion injury. As this is a feasibility study, the clinical implications of our findings will require further in vivo investigation on larger numbers of ischaemic‐reperfused pig hearts.

Comparison of intracoronary versus intravenous adenosine-induced maximal hyperemia for fractional flow reserve measurement: A systematic review and meta-analysis.

We sought to perform a systematic review and meta-analysis of the available literature comparing fractional flow reserve (FFR) measurements after administration of adenosine using intracoronary (IC) bolus versus standard continuous intravenous (IV) infusion. FFR is considered the gold standard for invasive assessment of coronary lesions of intermediate severity. IV adenosine is recommended to induce hyperemia; however, IC adenosine is widely used for convenience. The difference between IV and IC administration in lesions assessment is not well studied. We systematically searched MEDLINE and relevant databases for studies comparing IV with IC adenosine administration for FFR measurement. We reviewed data pertaining to adenosine doses, side effects, and FFR values. Eight studies addressing the primary question were identified. Dose of IC adenosine varied between 36 and 600 μg. Compared to IV adenosine infusion, the sensitivity of IC administration is 0.805 (95% confidence interval [95% CI]: 0.664-0.896; p < .001), specificity is 0.965 (95% CI: 0.932-0.983; p < .001), positive likelihood ratio is 24.218 (95% CI: 12,263-47.830; p < .001), negative likelihood ratio is 0.117 (95% CI: 0.033-0.411; p < .01), and diagnostic odds ratio is 274.225 [95% CI: 92.731-810.946; p < .001]. Overall, hemodynamic side effects and symptoms were reported more frequently with IV adenosine. The available literature suggests that IC adenosine is well tolerated and may provide equivalent diagnostic accuracy compared to IV administration. However, variability in dosing regimens does not allow definitive conclusions regarding noninferiority of IC approach compared to IV administration.

Utility and safety of adenosine challenge for subtle ventricular pre‐excitation in the pediatric population

Adenosine challenge (AC) can be used to evaluate possible Wolff-Parkinson-White (WPW) pattern on an electrocardiogram (ECG). Despite the use of this technique, there is a paucity of studies in the pediatric population evaluating the efficacy, safety, and outcomes of this testing modality. All ACs performed from January 2009 to June 2017 were retrospectively reviewed. Patient demographics, adenosine dosing, results, adverse effects, and outcomes including results of electrophysiology studies (EPS) were reviewed. Analysis was conducted between AC positive and negative cohorts. ECG criteria of shortest PR interval, longest QRS duration, and the number of suspected pre-excited leads were evaluated for inter-rater reliability and correlation to positive AC. Fifty-six AC (n = 51) were performed (median age, 13.8; range, 0.3-20 years). Forty-one AC were pre-EPS and 15 post-EPS due to concern for recurrent WPW. Thirty-one (76%) pre-EPS AC were negative, 9 (22%) positive, and 1 (2%) equivocal. EPS was performed following seven positive AC revealing 5 (71%) left posterior and 2 (29%) right posteroseptal AP. The 15 post-EPS AC were all found to be negative. Mean effective adenosine dose was 0.2 ± 0.11 mg/kg. No adverse events were reported. Mean follow up duration after AC was 314 ± 482 days with no documented arrhythmias. Adenosine challenge is an effective and safe testing modality for subtle WPW in the pediatric population. In our population, there were no adverse events or documented arrhythmias in patients following a negative study.

Atrial fibrillation with hemodynamic instability after the use of the third dose of adenosine during surgery for 7 intracranial aneurysms

Adenosine-induced asystole is a technique that prevents and controls the intraoperative rupture of cerebral aneurysm, facilitating temporary, and/or definitive clipping of the aneurysm. This is the case of a 58-year-old woman who underwent clipping of 7 intracranial aneurysms, who was induced asystole with adeno-sine 3 times and developed atrial fibrillation with hemodynamic instability after the last dose. Adenosine has been shown to be useful and safe, however, its use should be planned and possible cardiological complications should be considered.

A Novel Drug to Reduce Myocardial Infarct Size, Even When Administered After Coronary Artery Reperfusion

Despite the thousands of studies on drug therapy designed to reduce myocardial infarct size (IS), almost none have been successfully translated to the clinics. A major reason for failure is that many of these drugs are only effective when administered before coronary artery reperfusion (CAR), which limits their utility in the clinical setting, where CAR must be instituted immediately in patients after the myocardial infarction (MI) diagnosis has been made, not leaving time for drug therapy. It is also important that the drug does not increase myocardial oxygen consumption. In our prior work on the adenylyl cyclase type 5 (AC5) knock out (KO) mouse model, we found that it enhanced longevity, protected against diabetes and obesity, improved exercise performance and reduced IS after coronary artery occlusion (CAO) and CAR. Based on these studies, and since it is difficult to delete genes in humans, we developed a novel pharmacological candidate to inhibit AC5, named C90. C90 reduced AC activity and cAMP in response to forskolin more than vehicle, (12.9±1.9 vs. 14.2 ± 3.1 pmol/mg/min). However, in AC5 KO C90 no longer reduced cAMP in response to forskolin, indicating its selectivity for AC5 inhibition. The goal of this investigation was to examine the new AC5 inhibitor, C90, and compare its efficacy in reducing IS when the drug was delivered after CAR with that of adenosine, the gold standard for ischemic cardioprotection. Wild type (WT) mice were subjected to 30 min CAO followed by 24 hours CAR. C90 or vehicle was then administered at 5 min after CAR by intravenous (IV) administration at doses of 0.01, 0.03, 0.06, 0.6, and 1.2 mg/kg. The area at risk was similar in all groups, determined by triphenyltetrazolium chloride (TTC) staining. IS was reduced in a dose‐response manner by C90. IS was reduced by 32% at a dose of 0.06 mg/kg of C90, whereas the same dose of adenosine reduced IS similarly when administered before CAR but failed to reduce IS when administered after CAR. C90 further reduced IS by 64% at a dose of 0.6 mg/kg and by 71% at a dose of 1.2 mg/kg. When C90 was delivered at 10 min after CAR, it still IS by 50% and 53% at doses of 0.6 mg/kg and 1.2 mg/kg, respectively. In addition, LV ejection fraction (LV EF) was also examined at 4 weeks after myocardial infarction in mice, and was preserved in the C90 group (LVEF = 65±1.6%) vs. the vehicle group (LVEF = 52±2.9%). C90 also reduced IS by 49% in the Watanabe rabbit, model of atherosclerosis. Thus, C90, an inhibitor of AC5, is a novel target for clinical development, since it reduces myocardial IS when delivered after reperfusion, a key feature for patients coming to the emergency room, where reperfusion must be carried out before additional therapy. An additional advantageous feature of C90 and inhibition of AC5, is that it reduces beta‐adrenergic receptor signaling and myocardial oxygen consumption, which are important for patients with heart disease.Support or Funding InformationNIH R21AG053514; NIH R44 HL142390; NIH R44HL112512This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cardiovascular effects of two adenosine constant rate infusions in anaesthetized dogs

ObjectiveAdenosine induces vasodilatation. The aim of this study was to investigate cardiovascular effects of two adenosine constant rate infusion (CRI) doses in dogs. Study designExperimental, longitudinal repeated measure design. AnimalsTen healthy purpose-bred Beagle dogs. MethodsEach dog was sedated with butorphanol. Anaesthesia was induced with propofol intravenously and maintained with sevoflurane (inspired oxygen fraction = 47–55%). Controlled mechanical ventilation was used to maintain normocapnia. Two doses of adenosine were administered as CRIs to each dog: 140 μg kg–1 minute–1 (A140) followed by 280 μg kg–1 minute–1 (A280). Pulse rate, invasive arterial pressure and stroke volume (by magnetic resonance phase contrast angiography) were measured at baseline, 3 minutes after starting adenosine and 3 and 10 minutes after discontinuing adenosine. Cardiac output, cardiac index and approximated systemic vascular resistances (approximate SVR) were calculated. Additionally, arterial blood gases, co-oximetry, electrolytes, glucose and lactate were measured and oxygen content and delivery calculated. One-way repeated measures analysis of variance (p < 0.05) was used for data analysis. ResultsA140 and A280 resulted in a significant decrease in arterial blood pressure [systolic (p = 0.008), mean (p = 0.003), and diastolic arterial pressure (p = 0.004)] and approximate SVR (p = 0.008) compared with baseline. No significant changes were detected for the other variables. All values returned to baseline within 3 minutes after adenosine discontinuation. Conclusions and clinical relevanceAdenosine CRI decreases arterial pressure by vasodilatation in healthy dogs. No additional effects were observed with the higher dose. The effects in compromised dogs remain to be investigated.