Preoperative activation of the renin-angiotensin system and myocardial injury in noncardiac surgery: exploratory mechanistic analysis of the SPACE randomised controlled trial.

Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.

Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles).

The lifetime risk of surgery in England: a nationwide observational cohort study.

Background: The average number of times a person will have surgery in their lifetime, and the amount of surgical healthcare resources they use, is unknown. Lifetime risk is a measure of the risk of an average person having a specific event within their lifetime. We report the lifetime risk of surgery and the change observed during the first year of the COVID-19 pandemic.

Preoperative N-terminal pro-B-type natriuretic peptide and myocardial injury after stopping or continuing renin-angiotensin system inhibitors in noncardiac surgery: a prespecified analysis of a phase 2 randomised controlled multicentre trial.

Background: Patients with elevated preoperative plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP >100 pg ml) experience more complications after noncardiac surgery. Individuals prescribed renin-angiotensin system (RAS) inhibitors for cardiometabolic disease are at particular risk of perioperative myocardial injury and complications. We hypothesised that stopping RAS inhibitors before surgery increases the risk of perioperative myocardial injury, depending on preoperative risk stratified by plasma NT-proBNP concentrations.

Transauricular nerve stimulation in acute ischaemic stroke requiring mechanical thrombectomy: Protocol for a phase 2A, proof-of-concept, sham-controlled randomised trial.

Background: Labile blood pressure after acute ischaemic stroke requiring mechanical thrombectomy is independently associated with poor patient outcomes.

Objectives: This study protocol describes is designed to determine whether transauricular nerve stimulation, improves baroreflex sensitivity, reduces blood pressure variability in the first 24 hours after acute ischaemic stroke requiring mechanical thrombectomy.

Design: Phase 2a, Proof-of-concept, Sham-controlled Randomised Trial: Methods and Analysis: 36 individuals undergoing mechanical thrombectomy for acute ischaemic stroke with established hypertension aged >18 years will be randomly allocated to receive bilateral active or sham transauricular nerve stimulation for the duration of the mechanical thrombectomy procedure (AffeX-CT/001 investigational device).

Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial.

Background And Aims: Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear.

Methods: From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres.

Barriers to Quality Perioperative Care Delivery in Low- and Middle-Income Countries: A Qualitative Rapid Appraisal Study.

Background: Provision of timely, safe, and affordable surgical care is an essential component of any high-quality health system. Increasingly, it is recognized that poor quality of care in the perioperative period (before, during, and after surgery) may contribute to significant excess mortality and morbidity. Therefore, improving access to surgical procedures alone will not address the disparities in surgical outcomes globally until the quality of perioperative care is addressed.

Liberal or restrictive antimicrobial prophylaxis for surgical site infection: systematic review and meta-analysis of randomised trials.

Background: Antimicrobial prophylaxis is widely used to prevent surgical site infection. Amid growing concern about antimicrobial resistance, we determined the effectiveness of antimicrobial prophylaxis.

Methods: We searched MEDLINE, EMBASE, CENTRAL, and WHO-ICTRP between January 1, 1990 and January 1, 2020 for trials randomising adults undergoing surgery to liberal (more doses) or restrictive (fewer or no doses) perioperative antimicrobial prophylaxis.

Contemporary use of antimicrobial prophylaxis for surgical patients: An observational cohort study.

Background: Antimicrobial prophylaxis is commonly used to prevent surgical site infection (SSI), despite concerns of overuse leading to antimicrobial resistance. However, it is unclear how often antimicrobials are used and whether guidelines are followed.

Objectives: To describe contemporary clinical practice for antimicrobial prophylaxis including guideline compliance, the rate of postoperative infection and associated side effects.

Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

Introduction: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery.

Functional crosstalk between cardiac fibroblasts and adult cardiomyocytes by soluble mediators.

Aims: Crosstalk between cardiomyocytes and fibroblasts in physiological conditions and during disease remains poorly defined. Previous studies have shown that fibroblasts and myocytes interact via paracrine communication, but several experimental confounding factors, including the use of immature myocytes and the induction of alpha-smooth muscle actin (α-SMA) expression in fibroblasts by prolonged culture, have hindered our understanding of this phenomenon. We hypothesize that fibroblasts and myofibroblasts differentially affect cardiomyocytes viability, volume, and Ca(2+) handling via soluble mediators.

Characterisation of connexin expression and electrophysiological properties in stable clones of the HL-1 myocyte cell line.

The HL-1 atrial line contains cells blocked at various developmental stages. To obtain homogeneous sub-clones and correlate changes in gene expression with functional alterations, individual clones were obtained and characterised for parameters involved in conduction and excitation-contraction coupling. Northern blots for mRNAs coding for connexins 40, 43 and 45 and calcium handling proteins (sodium/calcium exchanger, L- and T-type calcium channels, ryanodine receptor 2 and sarco-endoplasmic reticulum calcium ATPase 2) were performed.

Influence of ivabradine on reverse remodelling during mechanical unloading.

Aims: Ivabradine (Iva) has shown beneficial structural and functional effects in clinical and experimental heart failure (HF), but its action in combination with mechanical unloading (MU), such as during treatment with left ventricular assist devices (LVAD), is unknown. The aim of this study was to investigate the effects of Iva during MU, in a rodent model of HF.

Methods And Results: We studied the chronic effects (4 weeks) of Iva (10 mg/kg/day) alone and in combination with MU [induced by heterotopic abdominal heart transplantation (HATx)] on whole-heart and cellular structure, function, and excitation-contraction (E-C) coupling in a rodent (rat) model of HF, 12 weeks post-left coronary artery (LCA) ligation.

Mechanical unloading reverses transverse tubule remodelling and normalizes local Ca(2+)-induced Ca(2+)release in a rodent model of heart failure.

Aims: Ca(2+)-induced Ca(2+) release (CICR) is critical for contraction in cardiomyocytes. The transverse (t)-tubule system guarantees the proximity of the triggers for Ca(2+) release [L-type Ca(2+) channel, dihydropyridine receptors (DHPRs)] and the sarcoplasmic reticulum Ca(2+) release channels [ryanodine receptors (RyRs)]. Transverse tubule disruption occurs early in heart failure (HF).