Sensational site: the sodium pump ouabain-binding site and its ligands.

Cardiotonic steroids (CTS), used by certain insects, toads, and rats for protection from predators, became, thanks to Withering's trailblazing 1785 monograph, the mainstay of heart failure (HF) therapy. In the 1950s and 1960s, we learned that the CTS receptor was part of the sodium pump (NKA) and that the Na/Ca exchanger was critical for the acute cardiotonic effect of digoxin- and ouabain-related CTS. This "settled" view was upended by seven revolutionary observations.

Whither digitalis? What we can still learn from cardiotonic steroids about heart failure and hypertension.

Cloning of the "Na pump" (Na,K-ATPase or NKA) and identification of a circulating ligand, endogenous ouabain (EO), a cardiotonic steroid (CTS), triggered seminal discoveries regarding EO and its NKA receptor in cardiovascular function and the pathophysiology of heart failure (HF) and hypertension. Cardiotonic digitalis preparations were a preferred treatment for HF for two centuries, but digoxin was only marginally effective in a large clinical trial (1997). This led to diminished digoxin use.

Inverse salt sensitivity: an independent risk factor for cardiovascular damage in essential hypertension.

Objective: Salt sensitivity is a powerful risk factor for cardiovascular (CV) disease and mortality in both normotensive and hypertensive patients. We investigated the predictive value of the salt sensitivity phenotype in the development of CV events and hypertensive target organ damage (TOD) among essential hypertensive patients.

Methods: Eight hundred forty-four naive hypertensive patients were recruited and underwent an acute saline test during which blood pressure (BP) displayed either no substantial variation (salt-resistant, SR individuals), an increase (salt-sensitive, SS), or a paradoxical decrease (inverse salt-sensitive, ISS).

Outcomes in adults living with frailty receiving cardiopulmonary resuscitation: A systematic review and meta-analysis.

Background: Frailty is a clinical expression of adverse ageing which could be a valuable predictor of outcomes from cardiac arrest. The aim of this systematic review was to evaluate survival outcomes in adults living with frailty versus adults living without frailty receiving cardiopulmonary resuscitation (CPR) following cardiac arrest.

Methods: A comprehensive search of MEDLINE, EMBASE, CINAHL, and Web of Science databases was performed using pre-defined search terms, with no date or language restrictions applied.

Practical considerations in the management of inhaled prostacyclin therapy for pulmonary hypertension associated with interstitial lung disease (WHO group 3).

Pulmonary hypertension (PH), as a consequence of lung disease or hypoxia, has been classified as Group 3 PH by the World Symposium on Pulmonary Hypertension. The most common lung diseases associated with Group 3 PH are chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). PH in ILD (PH-ILD) is associated with reduced exercise capacity, greater supplemental oxygen needs, decreased quality of life, and earlier death compared to ILD alone.