Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in the world. Because the key to developing innovative therapies that limit the onset and the progression of AF is to fully understand the underlying molecular mechanisms of AF, the aim of the present narrative review is to report the most recent advances in the potential role of the adenosinergic system in the pathophysiology of AF. After a comprehensive approach describing adenosinergic system signaling and the mechanisms of the initiation and maintenance of AF, we address the interactions of the adenosinergic system's signaling with AF. Indeed, adenosine release can activate four G-coupled membrane receptors, named A1, A2A, A2B and A3. Activation of the A2A receptors can promote the occurrence of delayed depolarization, while activation of the A1 receptors can shorten the action potential's duration and induce the resting membrane's potential hyperpolarization, which promote pulmonary vein firing, stabilize the AF rotors and allow for functional reentry. Moreover, the A2B receptors have been associated with atrial fibrosis homeostasis. Finally, the adenosinergic system can modulate the autonomous nervous system and is associated with AF risk factors. A question remains regarding adenosine release and the adenosine receptors' activation and whether this would be a cause or consequence of AF.

Adenosine, Adenosine Receptors and Neurohumoral Syncope: From Molecular Basis to Personalized Treatment.

Adenosine is a ubiquitous nucleoside that is implicated in the occurrence of clinical manifestations of neuro-humoral syncope (NHS). NHS is characterized by a drop in blood pressure due to vasodepression together with cardio inhibition. These manifestations are often preceded by prodromes such as headaches, abdominal pain, feeling of discomfort or sweating. There is evidence that adenosine is implicated in NHS. Adenosine acts via four subtypes of receptors, named A1 (A1R), A2A (A2AR), A2B (A2BR) and A3 (A3R) receptors, with all subtypes belonging to G protein membrane receptors. The main effects of adenosine on the cardiovascular system occurs via the modulation of potassium ion channels (IK Ado, K ATP), voltage-gate calcium channels and via cAMP production inhibition (A1R and A3R) or, conversely, through the increased production of cAMP (A2A/BR) in target cells. However, it turns out that adenosine, via the activation of A1R, leads to bradycardia, sinus arrest or atrioventricular block, while the activation of A2AR leads to vasodilation; these same manifestations are found during episodes of syncope. The use of adenosine receptor antagonists, such as theophylline or caffeine, should be useful in the treatment of some forms of NHS. The aim of this review was to summarize the main data regarding the link between the adenosinergic system and NHS and the possible consequences on NHS treatment by means of adenosine receptor antagonists.

Technical and biological review of authorized medical devices for platelets-rich plasma preparation in the field of regenerative medicine.

Platelet-rich plasma (PRP) has seen increased interest and utilization over the past decade, particularly in the field of musculoskeletal disease. This growth has been accompanied by the development of medical devices to realize PRP preparation which includes blood collection, centrifugation, and PRP isolation. The final PRP composition is directly influenced by this preparation step and absence of biological quality control led to a lack of comparability between PRP products that could explain the large variability in the clinical benefit of PRP reported in literature. To circumvent this issue, the scientific community developed different PRP classifications but none of them have been adopted. The goal of this review is to furnish both technical and biological characteristics from PRP commercial systems. On review of 1379 studies, 105 studies were selected according to inclusion criteria for technical analysis and led to the identification of 50 commercial systems that have been classified in three technical categories based on the blood harvesting technique (tubes, syringes or bags). Twelve studies were selected and sufficiently describe biological characteristics from only 14 commercial systems from the 50 identified in the technical analysis. Inclusion of duplicates characterization from a same PRP system lead to the final analysis of 36 PRP preparations that met the inclusion criteria of the biological analysis. All these PRP preparations have been classified among the seven existing classifications. Comparison from all biological parameters and classifications revealed a large heterogeneity among the available current PRP commercial systems. Index of biological sensitivity of classifications to distinguish PRP preparations were also variable. Although these findings should help clinicians in selecting a system that meets their specific needs, this also raises the question to standardize the parameters to biologically define PRP preparation among users and to systematically performed PRP qualification when used.

Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19.

Beside the commonly described pulmonary expression of the coronavirus disease 2019 (COVID-19), major vascular events have been reported. The objective of this study was to investigate whether increased levels of circulating endothelial cells (CECs) might be associated with severe forms of COVID-19. Ninety-nine patients with COVID-19 were enrolled in this retrospective study. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. Together, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.