Adenosinergic System and Neuroendocrine Syncope: What Is the Link?

Although very common, the precise mechanisms that explain the symptomatology of neuroendocrine syncope (NES) remain poorly understood. This disease, which can be very incapacitating, manifests itself as a drop in blood pressure secondary to vasodilation and/or extreme slowing of heart rate. As studies continue, the involvement of the adenosinergic system is becoming increasingly evident. Adenosine, which is an ATP derivative, may be involved in a large number of cases. Adenosine acts on G protein-coupled receptors with seven transmembrane domains. A1 and A2A adenosine receptor dysfunction seem to be particularly implicated since the activation leads to severe bradycardia or vasodilation, respectively, two cardinal symptoms of NES. This mini-review aims to shed light on the links between dysfunction of the adenosinergic system and NHS. In particular, signal transduction pathways through the modulation of cAMP production and ion channels in relation to effects on the cardiovascular system are addressed. A better understanding of these mechanisms could guide the pharmacological development of new therapeutic approaches.

Impact of the implementation of a trauma system on compliance with evidence-based clinical management guidelines in penetrating thoracic trauma.

PURPOSE: Since 2014, a trauma system (TS) for the Provence-Alpes-Cote-d'Azur (PACA) region has been set up with protocols based on the European guidelines for the management of bleeding trauma patients. The present study aims to assess compliance with protocols in penetrating thoracic trauma on admission to a level I trauma centre and to determine whether compliance impacts morbidity and mortality. METHODS: This multicentric pre-post study included all penetrating thoracic trauma patients referred to Marseille area level I centres between January 2009 and December 2019. On the basis of the European guidelines, eight objectively measurable recommendations concerning the in-hospital trauma care for the first 24 h were analysed. Per-patient and per-criterion compliance rates and their impact on morbidity and mortality were evaluated before and after TS implementation. RESULTS: A total of 426 patients were included. No differences between the two groups (before and after 2014) were reported for demographics or injury severity. The median (interquartile range) per-patient compliance rate increased from 67% [0.50; 0.75] to 75% [0.67; 1.0] (p < 0.01) after implementation of a TS. The 30-day morbidity-mortality was, respectively, of 17% (30/173) and 13% (32/253) (p = 0.18) before and after TS implementation. A low per-patient compliance rate was associated with an increase in the 30-day morbidity-mortality rate (p < 0.01). Severity score-adjusted per-patient compliance rates were associated with decreased 30-day morbidity-mortality (odds ratio [IC 95%] = 0.98 [0.97; 0.99] p = 0.01). CONCLUSION: Implementation of a TS was associated with better compliance to European recommendations and better outcomes for severe trauma patients. These findings should encourage strict adherence to European trauma protocols to ensure the best patient outcomes.

Acute mesenteric ischemia: which predictive factors of delayed diagnosis at emergency unit?

PURPOSE: Acute mesenteric ischemia (AMI) is frequently diagnosed late, leading to a poor prognosis. Our aims were to identify predictive factors of delayed diagnosis and to analyze the outcomes of patients with AMI admitted in emergency units. METHODS: All the patients with AMI (2015-2020), in two Emergency units, were retrospectively included. Two groups were defined according to the time of diagnosis between the arrival at emergency unit and the CT scan: ≤ 6 h (early), > 6 h (delayed). RESULTS: 119 patients (mean age = 71 ± 7 years) were included. The patients with a delayed diagnosis (n = 33, 28%) were significantly associated with atypical presentation, including lower rates of abdominal pain (73 vs 89%, p = 0.003), abdominal tenderness (33 vs 43%, p = 0.03), and plasma lactate (4 ± 2 vs 6 ± 7 mmol/l, p = 0.03) when compared with early diagnosis. After multivariate analysis, the absence of abdominal pain was the only independent predictive factor of delayed diagnosis (Odd Ratio = 0.17; 95% CI = 0.03-0.88, p = 0.03). Patients with delayed diagnosis tended to be associated to lower rates of revascularization (9 vs 17%, p = 0.4), higher rates of major surgical morbidity (90 vs 57%, p = 0.1), longer length of stay (16 ± 23 vs 13 ± 15 days, p = 0.4) and, at the end of follow-up, higher rate of short small bowel syndrome (18 vs 7%, p = 0.095). CONCLUSION: AMI is a challenge for emergency physicians. History of patient, physical exam, biological data are not sufficient to diagnose AMI. New biomarkers, and awareness of emergency physicians should improve and accelerate the diagnosis of AMI.

Time to source control and outcome in community-acquired intra-abdominal infections: The multicentre observational PERICOM study.

BACKGROUND: Optimal management of community-acquired intra-abdominal infections (IAI) requires timely surgical source control and adequate anti-infective treatment. OBJECTIVE: To describe the initial management of community-acquired IAI admitted to the emergency department and assess the association between the length of time to either diagnosis or therapeutic procedures and patient outcomes. DESIGN: A prospective, multicentre, observational study. SETTING: Thirteen teaching hospitals in France between April 2018 and February 2019. PATIENTS: Two hundred and five patients aged at least 18 years diagnosed with community-acquired IAI. MAIN OUTCOME MEASURES: The primary outcome was hospital length of stay. The secondary outcome was hospital mortality. RESULTS: Patients had a mean age of 56 (± 21) years and a median [interquartile] SAPS II of 26 [17 to 34]. Among the study cohort, 18% were postoperatively transferred to intensive care unit and 7% had died by day 28. Median [IQR] time to imaging, antibiotic therapy and surgery were 4 [2 to 6], 7.5 [4 to 12.5] and 9 [5.5 to 17] hours, respectively. The length of time to surgical source control [0.99, 95% confidence interval (CI), 0.98 to 0.99], SOFA greater than 2 [0.36 (95% CI, 0.26 to 0.651)], age greater than 60 years [0.65 (95% CI, 0.45 to 0.94)], generalized peritonitis [0.7 (95% CI, 0.56 to 0.89)] and laparotomy surgery [0.657 (95% CI, 0.42 to 0.78)] were associated with longer hospital length of stay. The duration of time to surgical source control [1.02 (95% CI, 1.01 to 1.04)], generalized peritonitis [2.41 (95% CI, 1.27 to 4.61)], and SOFA score greater than 2 [6.14 (95% CI, 1.40 to 26.88)] were identified as independent risk factors for 28-day mortality. CONCLUSION: This multicentre observational study revealed that the time to surgical source control, patient severity and generalized peritonitis were identified as independent risk factors for increased hospital LOS and mortality in community-acquired IAI. Organisational strategies to reduce the time to surgical management of intra-abdominal infections should be further evaluated. STUDY REGISTRATION: ClinicalTrials.gov on 1 April 2018, NCT03544203.

Safety, Pharmacokinetic, and Pharmacodynamic Study of a Sublingual Formula for the Treatment of Vasovagal Syncope.

BACKGROUND: Vasovagal syncope is a common cause of syncope which, if recurrent, can have multiple negative consequences such as injury and occupational disability. Various medications can be used to decrease the recurrence of vasovagal syncope but there are no drugs that can be used by patients to interrupt a perceived vasovagal episode. METHODS: A phase I study was performed to evaluate the tolerability and safety of a gel formulation containing capsaicin (1 mg), phenylephrine HCL (PE) and caffeine citrate (200 mg) (CPC) in normal adult volunteers. Secondary objectives were to characterize the pharmacokinetics (PK) of the CPC formulation and the highest dose of PE needed to achieve a target increase in systolic BP of at least 40 mmHg. After receiving the first dose, a second dose of the CPC mixture was administered at 2 h. Suboptimal changes in systolic blood pressure (SBP) were noted at PE doses of 0.6, 1.2, and 1.8 mg, therefore a second cohort was studied at PE doses of 10, 20, and 30 mg. Blood samples were collected in rapid sequence and were assayed for all three drugs. RESULTS: A total of 17 subjects received the drug with no serious adverse effects reported. All doses were well tolerated, although the capsaicin content usually caused expected temporary oral and gastric discomfort. One subject did not complete the study because of a vasovagal reaction that was associated with the frequent blood sampling. There was a 5-25 min lag in the appearance of measurable blood concentrations of capsaicin and phenylephrine. Most subjects had baseline caffeine concentrations from dietary use, with a gradual increase noted after 15 min consistent with GI absorption. Although the intended criterion of a 40 mmHg increase in SBP was not reached, a clinically significant increase in BP for at least 15 min was noted in the six subjects who received the highest dose of PE (30 mg), with a gradual decline over the next 2 h. CONCLUSION: The ternary mixture of capsaicin, phenylephrine, and caffeine was well tolerated when administered as two sublingual/oral doses over a 2-h period.

Flow cytometry evaluation of infection-related biomarkers in febrile subjects in the emergency department.

Aim: In an Emergency Department (ED), the etiological identification of infected subjects is essential. 13 infection-related biomarkers were assessed using a new flow cytometry procedure. Materials & methods: If subjects presented with febrile symptoms at the ED, 13 biomarkers' levels, including CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), were tested and compared with clinical records. Results: Among 50 subjects, 78% had bacterial infections and 8% had viral infections. nCD64 showed 82% sensitivity and 91% specificity for identifying subjects with bacterial infections. mCD169, HLA-ABC ratio and HLA-DR on monocytes had high values in subjects with viral infections. Conclusion: Biomarkers showed promising performances to improve the ED's infectious stratification.

Adenosine plasma level in patients with paroxysmal or persistent atrial fibrillation and normal heart during ablation procedure and/or cardioversion.

The mechanism of atrial fibrillation (AF) in patients with normal heart remains unclear. While exogenous adenosine can trigger AF, nothing is known about the behavior of endogenous adenosine plasma level (APL) at the onset of AF and during ablation procedure. Ninety-one patients (68 with paroxysmal AF: 40 males, 66 ± 16 years; 23 with persistent AF: 14 males, 69 ± 11 years) and 18 controls were included. Among paroxysmal patients: i) medical therapy alone was performed in 45 cases and ablation procedure in 23. AF was spontaneously resolutive in 6 cases; ii) 23 underwent ablation procedure and blood was collected simultaneously in a brachial vein and in the left atrium; 17 were spontaneously in sinus rhythm while 6 were in sinus rhythm after direct current cardioversion. Among persistent patients: i) in 17 patients, blood samples were collected in a brachial vein before and after direct current cardioversion; ii) in 6 patients, blood samples were collected simultaneously in a brachial vein and in left atrium before and after cardioversion during ablation procedure. CV-APL was higher in patients with persistent AF vs patients with paroxysmal AF (median [range]: 0.9[0.6-1.1] vs 0.7[0.4-1.1] µM; p < 0.001). In patients with paroxysmal AF, LA-APL increased during the AF episode (0.95[0.85-1.4] vs 2.7[1.5-7] µM; p = 0.03) and normalized in sinus rhythm after DCCV. In patients with persistent AF, LA-APL was higher than CV-APL (1.2[0.7-1.8] vs 0.9[0.6-1.1] µM; p < 0.001), and both normalized in sinus rhythm (CV-APL: 0.8[0.6-1.1] vs 0.75[0.4-1] µM; p = 0.03), (LA-APL: 1.95[1.3-3] vs 1[0.5-1.15] µM; p = 0.03). The occurrence of AF is associated with a strong increase of APL in the atrium. The cause of this increase needs further investigations.

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

According to recent literature, pretreatment with a P2Y12 ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y12 ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y12 ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y12 ADP receptor antagonist pretreatment.

Short-term effects of low-volume resuscitation with hypertonic saline and hydroxyethylstarch in an experimental model of lung contusion and haemorrhagic shock.

OBJECTIVES: This study aimed to assess the short-term respiratory tolerance and haemodynamic efficiency of low-volume resuscitation with hypertonic saline and hydroxyethylstarch (HS/HES) in a pig model of lung contusion and controlled haemorrhagic shock. We hypothesised that a low-volume of HS/HES after haemorrhagic shock did not impact contused lungs in terms of extravascular lung water 3hours after trauma. METHODS: A lung contusion resulting from blunt chest trauma was induced in 28 anaesthetised female pigs with five bolt-shots to the right thoracic cage, followed by haemorrhagic shock and fluid resuscitation. Pigs were randomly allocated into two groups: fluid resuscitation by 4ml/kg of HS/HES, or fluid resuscitation by 10ml/kg of normal saline (NS). Monitoring was based on transpulmonary thermodilution and a pulmonary artery catheter. After 3h, animals were euthanized to measure extravascular lung water (EVLW) by gravimetry. RESULTS: Blunt chest trauma was followed by a transient collapse and hypoxaemia in both groups. Post-mortem gravimetric assessment demonstrated a significant difference between EVLW in the NS-group (8.1±0.7ml/kg) and in the HS/HES-group (6.2±0.6ml/kg, P=0.038). Based on a pathological EVLW threshold of > 7ml/kg, results indicated that only the NS-group experienced moderate pulmonary oedema, contrary to the HS/HES-group. After haemorrhagic shock, HS/HES infusion enabled the restoration of effective mean arterial pressure and cardiac index. Intrapulmonary shunting increased transiently after fluid resuscitation but there was no significant impairment of oxygenation. CONCLUSION: In this pig model of lung contusion, the short-term assessment of fluid resuscitation after haemorrhagic shock with 4ml/kg of HS/HES showed that pulmonary oedema was avoided compared to fluid resuscitation with 10ml/kg of NS.

Timing of Coronary Invasive Strategy in Non-ST-Segment Elevation Acute Coronary Syndromes and Clinical Outcomes: An Updated Meta-Analysis.

OBJECTIVES: The aim of this study was to compare an early versus a delayed invasive strategy in non-ST-segment elevation acute coronary syndromes by performing a meta-analysis of all available randomized controlled clinical trials. BACKGROUND: An invasive approach is recommended to prevent death and myocardial infarction in non-ST-segment elevation acute coronary syndromes. However, the timing of angiography and the subsequent intervention, when required, remains controversial. METHODS: A previous meta-analysis of 7 randomized clinical trials comparing early and delayed invasive strategies in non-ST-segment elevation acute coronary syndromes with 3 new randomized clinical trials identified in a search of the published research (n = 10 trials, n = 6,397 patients) was updated. RESULTS: The median time between randomization and angiography ranged from 0.5 to 14.0 h in the early group and from 18.3 to 86.0 h in the delayed group. There was no difference in the primary endpoint of mortality (4% vs. 4.7%; random-effects odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.67 to 1.09; p = 0.20; I2 = 0%). The rate of myocardial infarction was also similar (6.7% vs. 7.7%; random-effects OR: 0.88; 95% CI: 0.53 to 1.45; p = 0.62; I2 = 77.5%). An early strategy was associated with a reduction in recurrent ischemia or refractory angina (3.8% vs. 5.8%; random-effects OR: 0.54; 95% CI: 0.40 to 0.74; p < 0.01; I2 = 28%) and a shorter in-hospital stay (median 112 h [interquartile range: 61 to 158 h] vs. 168 h [interquartile range: 90.3 to 192 h]; random-effects standardized mean difference -0.40; 95% CI: -0.59 to -0.21; p < 0.01; I2 = 79%). Major bleeding was similar in the 2 groups (3.9% vs. 4.2%; random-effects OR: 0.94; 95% CI: 0.73 to 1.22; p = 0.64; I2 = 0%). CONCLUSIONS: An early invasive strategy does not reduce the risk for death or myocardial infarction compared with a delayed strategy. Recurrent ischemia and length of stay were significantly reduced with an early invasive strategy.

Comparison of Ticagrelor Versus Prasugrel to Prevent Periprocedural Myonecrosis in Acute Coronary Syndromes.

Guidelines recommend a ticagrelor loading dose (LD) before PCI or a prasugrel LD at the time of percutaneous coronary intervention (PCI) in intermediate and high-risk non-ST-elevation acute coronary syndrome (NSTE-ACS). However, achieving an optimal PR inhibition at the time of PCI is critical to prevent adverse events and depends on the timing of LD intake in relation to PCI. We aimed to compare the rate of myonecrosis related to PCI in patients with NSTE-ACS receiving ticagrelor pretreatment versus prasugrel at the time of intervention. We prospectively randomized 213 patients with NSTE-ACS to a 180 mg of ticagrelor LD given as soon as possible after admission and before PCI or to a 60 mg LD of prasugrel given at the time of PCI. The primary end point was the rate of periprocedural myonecrosis as defined by an increase of >5 times the ninety-ninth percentiles in troponin-negative patients or a 20% increase in troponin-positive patients. The 2 groups were similar regarding baseline characteristics including clinical setting (p = 0.2). Procedural characteristics were also identical including the number of treated vessels and stenting procedures. Patients in the prasugrel group more often required emergent PCI (p = 0.001). Patients in the ticagrelor group had less periprocedural myonecrosis compared with those in the prasugrel group (19.8% vs 38.3%; p = 0.03). The rate of major adverse cardiovascular events and Bleeding Academic Research Consortium ≥2 at 1-month follow-up was low and similar between the 2 groups. In conclusion, a ticagrelor LD as soon as possible before PCI is superior to prasugrel at the time of PCI to prevent periprocedural myonecrosis in NSTE-ACS.

Impact of a computerized decision support system on compliance with guidelines on antibiotics prescribed for urinary tract infections in emergency departments: a multicentre prospective before-and-after controlled interventional study.

OBJECTIVES: Urinary tract infections (UTIs) are one of the leading reasons for antibiotic prescriptions in emergency departments (EDs), with half of these antibiotics being inappropriately prescribed. Our objective was to assess the impact of a computerized decision support system (CDSS) on compliance with guidelines on empirical antibiotic prescriptions (antibiotic and duration) for UTIs in EDs. METHODS: A multicentre prospective before-and-after controlled interventional study was conducted from 19 March to 28 October 2012. All adults diagnosed with community-acquired UTIs (cystitis, pyelonephritis or prostatitis) at three French EDs were included. The antibiotic therapy was considered compliant with guidelines if the antibiotic and the duration prescribed were in accordance with the national guidelines. Data were collected using electronic medical records. Paired tests were used when comparing periods within each ED and global analyses used multivariate logistic mixed models. RESULTS: Nine hundred and twelve patients were included during the 30 week study period. The CDSS was used in 59% of cases (182/307). The CDSS intervention improved the compliance of antibiotic prescriptions in only one ED in a bivariate analysis (absolute increase +20%, P = 0.007). The choice of the antibiotic was improved in multivariate analyses but only when the CDSS was used [OR = 1.94 (95% CI 1.13-3.32)]. The CDSS also changed the initial diagnosis in 23% of cases, in all three EDs. CONCLUSIONS: The CDSS only partially improved compliance with guidelines on antibiotic prescriptions in UTIs.

Ticagrelor versus prasugrel in diabetic patients with an acute coronary syndrome. A pharmacodynamic randomised study.

Optimal P2Y12 receptor blockade is critical to prevent ischaemic recurrence in patients undergoing percutaneous coronary intervention (PCI). We aimed to compare the level of platelet reactivity (PR) inhibition achieved by prasugrel and ticagrelor loading dose (LD) in diabetic acute coronary syndrome (ACS) patients undergoing PCI. We performed a single-center prospective open-label randomised trial. Patients with diabetes mellitus undergoing PCI for an ACS were randomised to receive prasugrel 60 mg or ticagrelor 180 mg. The primary endpoint of the study was the level of platelet reactivity (PR) assessed between 6 and 18 hours post-LD using the VASP index. We randomised 100 diabetic patients undergoing PCI for an ACS. No difference was observed in baseline characteristics between the two groups. In particular, the rate of patient receiving insulin therapy was identical (25 vs 28.6%; p =0.7). Ticagrelor achieved a significantly lower PR compared to prasugrel loading dose (17.3 ± 14.2 vs 27.7 ± 23.3%; p=0.009). In addition the rate of high on-treatment platelet reactivity, defined by a VASP ≥50%, tend to be lower in the ticagrelor group although the difference did not reach statistical significance (6 vs 16%; p=0.2). The rate of low on treatment PR was identical (60 vs 54%; p=0.8). The present study demonstrates that ticagrelor LD is superior to prasugrel LD to reduce PR in ACS patients with diabetes mellitus. Whether the higher potency of ticagrelor could translate into a clinical benefit should be investigated.

Assessing post-treatment platelet reactivity: a focus on patient selection and setting.

Dual antiplatelet therapy is critical to inhibit platelet reactivity in order to prevent ischemic recurrences in stented patients. However, studies have observed a variable blockade of the P2Y12 adenosine diphosphate receptor between patients following clopidogrel intake. This interindividual variability in the biological response is not uncommon with clopidogrel (about 50%) and even prasugrel (20%). High on-treatment platelet reactivity (HTPR) is correlated with thrombotic events following percutaneous coronary intervention. Several studies suggested that tailoring of antiplatelet therapy based on platelet reactivity (PR) monitoring could safely reduce the rate of major adverse cardiovascular events in HTPR patients. In addition, low on-treatment PR was recently associated with bleeding events both in patients treated with prasugrel and clopidogrel. Of importance, bleedings are associated with a poor prognosis in stented patients. Overall, the potential of PR monitoring to individualize antiplatelet therapy might benefit stented patients by reducing both ischemic and bleeding risks. However, such strategies remain to be evaluated in adequately designed large-scale randomized clinical trials.

A pig model for blunt chest trauma: no pulmonary edema in the early phase.

OBJECTIVE: Chest trauma remains a leading cause of trauma-death. Since lung contusion is one of the most important lesions implicated, the aim of this experimental study was to evaluate the cardiorespiratory consequences of an isolated lung contusion model. METHODS: Twenty-eight anesthetized pigs were studied during four hours. We induced a right lung contusion with five bolt shots (70 joules each) using a 22-caliber charge in twenty of them. Eight others pigs constituted the control group. The trauma consequences were assessed by histology, measurements of arterial oxygenation, plasma cytokines, pressure-volume mechanics, hemodynamic monitoring using the PiCCO system and a pulmonary artery catheter. The extra-vascular lung water was measured using the gravimetric method. RESULTS: Histology confirmed an isolated right lung contusion without cardiac injury. Compared to baseline values, the trauma group was characterized by a decrease in cardiac index (3.3 ± 0.8 vs 3.9 ± 1.2 l/min/m(2); P < .05) and mean arterial pressure (80 ± 21 vs 95 ± 16 mmHg; P < .05) without preload or afterload modification. Oxygenation (PaO2/FiO2: 349 ± 87 vs 440 ± 75; P < .05) and static compliance (26.3 ± 7.4 vs 30.3 ± 7.8 ml/cmH2O; P < .05) were also impaired during two hours compared to baseline. No edema was noticed in either group whatever the lung considered. All measured cytokines were below the detection threshold. CONCLUSIONS: An isolated right lung contusion is associated with rapid but transient cardiorespiratory impairments. Despite the large extent of the lung contusion, no pulmonary edema appeared during the period studied.

Search for adenosine A2A spare receptors on peripheral human lymphocytes.

Some ligand-receptor couples involve spare receptors, which are apparent when a maximal response is achieved with only a small fraction of the receptor population occupied. This situation favours cross-reactions with low-affinity ligands, which may be detrimental for cell signaling. In the case of the adenosine A2A receptors (A2AR), which have an immunosuppressive effect on lymphocytes through cAMP production, the presence of spare A2AR remains to be established. We examined the situation using patients over-expressing lymphocyte A2AR and an agonist-like mAb to A2AR. We found that maximal mAb binding and functional response varied among the patients whereas the dissociation constant and half-maximal effective concentration had similar mean values (0.19 and 0.18 µM, respectively). Lymphocyte A2AR expression was correlated to plasma adenosine level and A2AR occupation but not to A2AR response. These results are consistent with a lack of a reserve of functional A2AR on human lymphocytes as a general rule and suggest that the amount and functional state of the expressed A2AR determine the maximal level of the lymphocyte response to adenosine.

Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention.

BACKGROUND: The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS). OBJECTIVE: We aimed to evaluate the level of PR inhibition achieved by a 180 mg LD of ticagrelor and the rate of high on-treatment platelet reactivity (HTPR) in ACS patients undergoing PCI. METHODS: We performed a multicentre prospective observational study enrolling ACS patients undergoing PCI. Patients were included if they were admitted for ST-elevation myocardial infarction or non ST-elevation ACS. To assess PR, a VASP index was measured at least 6 and within 24 hours following a 180 mg LD of ticagrelor. HTPR was defined as a VASP index ≥50%. RESULTS: One hundred and fifteen patients were included: 31.3% of STEMI, 49.6% of NSTEMI and 19.1% of unstable angina. Following ticagrelor LD the mean VASP index was 17±14%. However the response to ticagrelor was not uniform with a small inter-individual variability: inter quartile range: 7.6-22.8% and a rate of HTPR of 3.5%. A high number of patients, 65.6%, had a VASP index <16%. None of the baseline characteristics of the study population was associated with PR. In addition, PR was similar in STEMI, NSTEMI and unstable angina (p=0.9). CONCLUSION: In ACS patients the level of PR inhibition achieved by a 180 mg loading dose of ticagrelor is not uniform and the rate of HTPR is 3.5%. A high proportion of patients exhibited a VASP index <16%.