Cardiovascular Stress Reactivity and Health: Recent Questions and Future Directions.

Objective: High cardiovascular reactions to psychological stress are associated with the development of hypertension, systemic atherosclerosis, and cardiovascular disease. However, it has become apparent that low biological stress reactivity also may have serious consequences for health, although less is known about the mechanisms of this. The objectives of this narrative review and opinion article are to summarize and consider where we are now in terms of the usefulness of the reactivity hypothesis and reactivity research, given that both ends of the reactivity spectrum seem to be associated with poor health, and to address some of the key criticisms and future challenges for the research area.

Neurobiological mechanisms of early life adversity, blunted stress reactivity and risk for addiction.

Blunted stress reactivity resulting from early exposure to stress during childhood and adolescence may increase vulnerability to addiction. Early life adversity (ELA) affects brain structure and function and results in blunted stress axis reactivity. In this review, we focus on the underlying neurobiological mechanisms associated with a blunted response to stress, ELA, and risk for addictive disorders.

Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis.

Background: The prevalence of ex vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear.

Methods: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes.

Enteral Nutrition in the Mechanically Ventilated Patient.

Mechanically ventilated patients are unable to take food orally and therefore are dependent on enteral nutrition for provision of both energy and protein requirements. Enteral nutrition is supportive therapy and may impact patient outcomes in the intensive care unit. Early enteral nutrition has been shown to decrease complications and hospital length of stay and improve the prognosis at discharge.

The role of genetics in stress effects on health and addiction.

Advances in stress research have yielded new insights into how stress exposure, in combination with genetics, can contribute to poor health outcomes. We review these topics with a special emphasis on early life stress and vulnerability to addiction. The direct effects of stress and our compensatory responses can modify our physiology and behavior during future stress episodes.

Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome.

Background: Both the adrenergic and renin-angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1-adrenergic and β1/2-adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity.

The behavioural, cognitive, and neural corollaries of blunted cardiovascular and cortisol reactions to acute psychological stress.

Recent research shows that blunted cardiovascular and cortisol reactions to acute psychological stress are associated with adverse behavioural and health outcomes: depression, obesity, bulimia, and addictions. These outcomes may reflect suboptimal functioning of the brain's fronto-limbic systems that are needed to regulate motivated behaviour in the face of challenge. In support of this, brain imaging data demonstrate fronto-limbic hypoactivation during acute stress exposure.

Critical Evaluation of Animal Models of Gastrointestinal Disorders.

Preclinical research remains an important tool for discovery and validation of novel therapeutics for gastrointestinal disorders. While in vitro assays can be used to verify receptor-ligand interactions and test for structural activity of new compounds, only whole-animal studies can demonstrate drug efficacy within the gastrointestinal system. Most major gastrointestinal disorders have been modeled in animals; however the translational relevance of each model is not equal.

Antiadrenergic autoimmunity in postural tachycardia syndrome.

Aims: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR).

Methods And Results: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro.

Temporal Trends of Digoxin Use in Patients Hospitalized With Heart Failure: Analysis From the American Heart Association Get With The Guidelines-Heart Failure Registry.

Objectives: The aim of this study was to assess temporal trends and factors associated with digoxin use at discharge among patients admitted with heart failure (HF).

Background: Digoxin has class IIa recommendations for treating HF with reduced ejection fraction (HFrEF) in the United States. Digoxin use, temporal trends, and clinical characteristics of HF patients in current clinical practice in the United States have not been well studied.

Prevalence of angiotensin II type 1 receptor (AT1R)-activating autoantibodies in primary aldosteronism.

Autoantibodies to the angiotensin II type 1 receptor (AT1R) have been reported in patients with primary aldosteronism, including aldosterone producing adenoma (APA) and idiopathic adrenal hyperplasia (IAH). Sera from 25 primary aldosteronism subjects (12 with IAH and 13 with APA) and 15 normotensive control subjects were assayed for AT1R autoantibodies by enzyme-linked immunosorbent assay and an AT1R-transfected cell-based bioassay. Nine of 12 IAH subjects (75%) and six of 13 APA subjects (46%) were positive for AT1R autoantibodies in the bioactivity assay.

A randomized, double-blind, placebo-controlled, crossover, dose-ranging multicenter study to determine the effect of sublingual nitroglycerin spray on exercise capacity in patients with chronic stable angina.

Background: Sublingual nitroglycerin increases exercise duration in patients with stable angina. Brief results from this study were published previously in German. Here, we more fully describe the study methodology, patient characteristics, and detailed results.

Autoantibody activation of beta-adrenergic and muscarinic receptors contributes to an "autoimmune" orthostatic hypotension.

Background: Orthostatic hypotension (OH) is characterized by an abnormal autonomic response to upright posture. Activating autoantibodies to β1/2-adrenergic (AAβ1/2AR) and M2/3 muscarinic receptors (AAM2/3R) produce vasodilative changes in the vasculature that may contribute to OH.

Methods: Immunoglobulin (Ig)G from 6 patients with idiopathic OH harboring autoantibodies and from 10 healthy control subjects were examined for: 1) β1AR and M2R activity with a perfused Purkinje fiber assay and PKA assay in H9c2 cells and 2) vasodilator β2AR and M3R activity using a pressurized cremaster resistance arteriole assay.

Development of cardiomyopathy and atrial tachyarrhythmias associated with activating autoantibodies to beta-adrenergic and muscarinic receptors.

A 71-year-old male with well-controlled hypertension developed atrial tachyarrhythmias in 2002 and a restrictive cardiomyopathy in 2006 to 2007. Sera from 1992, 2001, and 2006 to 2008 demonstrated activating autoantibodies against beta-adrenergic (AAbetaAR) and M2 muscarinic receptors (AAM2R). These sera have been characterized for bioactivity using in vitro assays of cardiac contractility and automaticity using a canine cardiac Purkinje fiber assay as well as protein kinase assay activation in H9c2 cells.

Opposing cardiac effects of autoantibody activation of β-adrenergic and M2 muscarinic receptors in cardiac-related diseases.

Background: Activating autoantibodies to β-adrenergic receptors (AAβ1/2AR) and M2 muscarinic receptors (AAM2R) have been reported in several cardiac diseases and may have pathophysiologic relevance. However, the interactions and relative effects of AAβ1AR, AAβ2AR and AAM2R on contractile function have not been characterized.

Methods: The inotropic effects of IgG from 18 selected patients with cardiomyopathy and/or atrial tachyarrhythmias positive by ELISA for antibodies to β1/2AR were studied using an isolated canine Purkinje fiber contractility assay.

Ischemic inactivation of G protein-coupled receptor kinase and altered desensitization of canine cardiac beta-adrenergic receptors.

Background: G protein-coupled receptor kinases (GRKs) modulate myocardial beta-adrenergic receptor (betaAR) signaling. We examined whether GRK activity was altered 6, 24, and 96 hours after left anterior descending coronary artery ligation (LAD CAL) in the dog.

Methods And Results: GRK activity was measured in arrhythmogenic subepicardial border zone (EBZ) tissue overlying the infarct and from nonischemic remote-site (RS) subepicardial tissue from the same animal.

Primary intracerebellar osteosarcoma arising within an epidermoid cyst.

The authors report a case of a primary extraskeletal osteosarcoma arising within an epidermoid cyst in the parenchyma of the cerebellum in a 64-year-old woman. On initial presentation, the tumor involved the midline cerebellum without attachment to the surrounding dura mater or calvarium. Complete medical and radiologic evaluation failed to reveal a primary skeletal or other extraskeletal osteosarcoma.