Serotonin Antagonism Improves Platelet Inhibition in Clopidogrel Low-Responders after Coronary Stent Placement: An In Vitro Pilot Study

Increased residual platelet reactivity remains a burden for coronary artery disease (CAD) patients who received a coronary stent and do not respond sufficiently to treatment with acetylsalicylic acid and clopidogrel. We hypothesized that serotonin antagonism reduces high on-treatment platelet reactivity. Whole blood impedance aggregometry was performed with arachidonic acid (AA, 0.5 mM) and adenosine diphosphate (ADP, 6.5 µM) in addition to different concentrations of serotonin (1–100 µM) in whole blood from 42 CAD patients after coronary stent placement and 10 healthy subjects. Serotonin increased aggregation dose-dependently in CAD patients who responded to clopidogrel treatment: After activation with ADP, aggregation increased from 33.7±1.3% to 40.9±2.0% in the presence of 50 µM serotonin (p<0.05) and to 48.2±2.0% with 100 µM serotonin (p<0.001). The platelet serotonin receptor antagonist ketanserin decreased ADP-induced aggregation significantly in clopidogrel low-responders (from 59.9±3.1% to 37.4±3.5, p<0.01), but not in clopidogrel responders. These results were confirmed with light transmission aggregometry in platelet-rich plasma in a subset of patients. Serotonin hence increased residual platelet reactivity in patients who respond to clopidogrel after coronary stent placement. In clopidogrel low-responders, serotonin receptor antagonism improved platelet inhibition, almost reaching responder levels. This may justify further investigation of triple antiplatelet therapy with anti-serotonergic agents

Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

<p>Abstract</p> <p>Background</p> <p>The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia.</p> <p>Methods</p> <p>First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion.</p> <p>Results</p> <p>Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours.</p> <p>Conclusions</p> <p>Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.</p

Sténose aortique : TAVI en première intention pour tous les patients ? [Aortic stenosis: TAVI for all patients?]

Over the last 21 years, the paradigm has shifted from an initial use of TAVI for inoperable aortic stenosis cases to recognition of its benefits for all categories of patients. Since 2021, the European Society of Cardiology has recommended first-line transfemoral TAVI from the age of 75 for all categories of patients with aortic stenosis (high, intermediate, low risk). However, in Switzerland, the Federal Office of Public Health currently places a restriction on the reimbursement of low-risk patients, which is expected to be reassessed in 2023. Surgery remains the best therapeutic option for patients with an unfavorable anatomy and for those whose life expectancy exceeds the potential durability of the valve. In this article we will discuss the evidence supporting TAVI, its current indications and initial complications as well as areas for improvement to potentially further expand its indications

CHAPTER 4. Ultra-high Field Imaging

MR spectroscopy (MRS) reveals information about the molecular structures underlying the MR signal. Properties such as chemical shift and scalar coupling cause a characteristic splitting of the resonance frequencies and following the numerical fitting of the acquired data to the corresponding basis spectra, these shifts can be used to distinguish different kinds of molecules. For in vivo applications, spatial localisation techniques for signal acquisition, such as STEAM or PRESS, and water signal suppression, i.e. CHESS or MEGA, are required. Using non-proton nuclei as target nuclei allows MRI to investigate in vivo metabolic processes and pathology non-invasively. These so-called X-nuclei impose increased technological and methodological demands, as the sensitivity and abundance are significantly lower compared to protons and their spin dynamics might be more sophisticated and complex. Nevertheless, the potential benefit of acquiring such data is tremendous both clinically and in research. The most prominent X-nuclei in vivo are 2H, 7Li, 13C, 17O, 19F, 23Na, 31P, 35Cl and 39K and a subset are discussed here. One of the applications that constitutes a ‘perfect fit’ for ultra-high field imaging is the depiction of brain anatomy. The usual challenges of ultra-high field imaging pertain but once overcome anatomical imaging of the brain is able to produce in vivo images with unprecedented resolution and contrast. The chapter concludes with a brief excursion into ‘emerging applications’ and includes phase and susceptibility imaging, quantitative susceptibility imaging and CEST-based imaging at ultra-high field