Background: Malignant ventricular arrhythmia (VA) is a major contributor to sudden cardiac death (SCD) in patients with pulmonary arterial hypertension (PAH)-induced right heart failure (RHF). Recently, dapagliflozin (DAPA), a sodium/glucose cotransporter-2 inhibitor (SGLT2i), has been found to exhibit cardioprotective effects in patients with left ventricular systolic dysfunction. In this study, we examined the effects of DAPA on VA vulnerability in a rat model of PAH-induced RHF. Methods: Rats randomly received monocrotaline (MCT, 60 mg/kg) or vehicle via a single intraperitoneal injection. A day later, MCT-injected rats were randomly treated with placebo, low-dose DAPA (1 mg/kg/day), or high-dose (3 mg/kg/day) DAPA orally for 35 days. Echocardiographic analysis, haemodynamic experiments, and histological assessments were subsequently performed to confirm the presence of PAH-induced RHF. Right ventricle (RV) expression of calcium (Ca²⁺) handling proteins were detected via Western blotting. RV expression of connexin 43 (Cx43) was determined via immunohistochemical staining. An optical mapping study was performed to assess the electrophysiological characteristics in isolated hearts. Cellular Ca²⁺ imaging from RV cardiomyocytes (RVCMs) was recorded using Fura-2 AM or Fluo-4 AM. Results: High-dose DAPA treatment attenuated RV structural remodelling, improved RV function, alleviated Cx43 remodelling, increased the conduction velocity, restored the expression of key Ca²⁺ handling proteins, increased the threshold for Ca²⁺ and action potential duration (APD) alternans, decreased susceptibility to spatially discordant APD alternans and spontaneous Ca²⁺ events, promoted cellular Ca²⁺ handling, and reduced VA vulnerability in PAH-induced RHF rats. Low-dose DAPA treatment also showed antiarrhythmic effects in hearts with PAH-induced RHF, although with a lower level of efficacy. Conclusion: DAPA administration reduced VA vulnerability in rats with PAH-induced RHF by improving RVCM Ca²⁺ handling.

Background and aims: Controversy remains regarding the prediction effects of different adiposity measure indicators for the risk of cardiovascular disease (CVD). Our study aimed to assess the associations of three traditional anthropometric indicators, namely, waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) as well as three non-traditional anthropometric indicators, namely, the Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), and body shape index (ABSI), with the risk of CVD among Southwest Chinese population.Methods: Our study was based on the Guizhou Population Health Cohort Study (GPHCS) conducted from 2010 to 2020. A total of 9,280 participants were recruited from 12 areas in Guizhou Province, China, from November 2010 to December 2012, and followed up for major chronic diseases until December 2020. A total of 7,837 individuals with valid data were included in this analysis. The gender-specific associations of WC, WHtR, BMI, CVAI, LAP, and ABSI with CVD were evaluated using Cox proportional hazards models. Receiver operating characteristic (ROC) curve analysis was used to estimate the prediction powers of different indicators for CVD.Results: No association of six indicators with CVD was observed among male participants. Female participants with either WC-based central obesity (HR: 1.82, 95% CI: 1.12–2.97) or WHtR-based central obesity (HR: 1.68, 95% CI: 1.07–2.64) had a higher risk of CVD, after adjusted for age, area, ethnic group, smoking, alcohol drinking, MET, previous history of diabetes, hypertension and dyslipidemia, medication use, and nutraceutical intake. Compared with female participants in the lowest quartile (Q1), those in the highest quartile (Q4) of WHtR (HR: 2.24, 95% CI: 1.17–4.27), CVAI (HR: 3.98, 95% CI: 1.87–8.49), and ABSI (HR: 1.94, 95% CI: 1.06–3.52) had an increased risk for incident CVD. CAVI showed the maximum predictive power of CVD with the biggest AUC of 0.687 (95% CI: 0.654–0.720) compared to other indicators in female participants.Conclusions: Visceral adiposity measures, especially CVAI, are stronger predictive indicators of CVD among female and not male participants in Southwest China. Different anthropometric indexes need to be combined to comprehensively assess health risks.

Avenanthramides (AVA) are a group of di-phenolic acids found only in oats and have shown antioxidant and anti-inflammatory effects in vitro and in vivo. Eccentric muscle contraction is intimately involved in rigorous exercise that activates systemic and local inflammatory responses. The objective of the study is to evaluate whether chronic AVA supplementation could attenuate peripheral inflammatory and immunological markers in human subjects in response to an acute bout of downhill running (DR). Eleven male and thirteen female subjects voluntarily participated in this double-blinded, randomized controlled study and were randomly divided into AVA-supplemented (AVA) or control (C) groups. All subjects conducted a DR protocol at − 10% grade with an intensity equivalent to 75% of their maximal heart rate. Blood samples were collected at rest and various time points (0-72 h) after DR (PRE). After an 8-week washout period, participants received two cookies daily containing either 206 mg/kg (AVA) or 0 mg/kg (C) AVA for 8 weeks. Following the oat supplementation regimen, the DR and blood sampling protocols were repeated (POST). Plasma inflammatory and immunological markers were measured using Multiplex immunoassay and muscle soreness was evaluated with pain rating scale. DR increased plasma creatine kinase (CK) activity (P < 0.01) during PRE, but the response was reduced at 24 and 48 h during POST vs. PRE regardless of AVA status (P < 0.05). Neutrophil respiratory burst (NRB) levels were elevated at 4 and 24 h (P < 0.05) during PRE but were significantly decreased at 0–48 h during POST vs. PRE (P < 0.05 or 0.01). Granulocyte-colony stimulating factor (G-CSF), the neutrophil stimulating cytokine, was also increased in response to DR but showed lower levels in AVA compared to C during POST vs. PRE (P < 0.05). Plasma interleukin-6 (IL-6) content showed an increase at 0 and 4 h during PRE and 0 h during POST (P < 0.01), whereas during POST there was a trend toward a lower IL-6 level in AVA vs. C (P = 0.082). Plasma levels of anti-inflammatory agent interleukin-1 receptor antagonist (IL-1Ra) showed an increase at 4 h during PRE, and was significantly elevated in AVA vs. C during POST. Both soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemoattractant protein-1 (MCP-1) contents increased at 0 and 24 h post DR during PRE as well as POST sessions, however, sVCAM-1 content was lower in AVA vs. C during POST (P < 0.05) and MCP-1 levels were below resting level at 24, 48 and 72 h during POST (P < 0.05). DR increased muscle pain at all post-DR time points (P < 0.01), but the pain level was alleviated by oat supplementation at 48 and 72 h during POST regardless of AVA treatment (P < 0.05). Oat AVA supplementation reduced circulatory inflammatory cytokines and inhibited expression of chemokines and cell adhesion molecules induced by DR. ClinicalTrials.gov identifier: NCT02584946 . Registered 23 October 2015.

Treatment of atrial fibrillation (AF) remains challenging despite significant progress in understanding its underlying mechanisms. The first detailed, quantitative theory of functional re-entry, the ‘leading circle’ model, was developed more than 40 years ago. Subsequently, in decades of study, an alternative paradigm based on spiral waves has long been postulated to drive AF. The rotor as a ‘spiral wave generator’ is a curved ‘vortex’ formed by spin motion in the two-dimensional plane, identified using advanced mapping methods in experimental and clinical AF. However, it is challenging to achieve complementary results between experimental results and clinical studies due to the limitation in research methods and the complexity of the rotor mechanism. Here, we review knowledge garnered over decades on generation, electrophysiological properties, and three-dimensional (3D) structure diversity of the rotor mechanism and make a comparison among recent clinical approaches to identify rotors. Although initial studies of rotor ablation at many independent centres have achieved promising results, some inconclusive outcomes exist in others. We propose that the clinical rotor identification might be substantially influenced by (i) non-identical surface activation patterns, which resulted from a diverse 3D form of scroll wave, and (ii) inadequate resolution of mapping techniques. With rapidly advancing theoretical and technological developments, future work is required to resolve clinically relevant limitations in current basic and clinical research methodology, translate from one to the other, and resolve available mapping techniques.

Sotagliflozin is a dual sodium-glucose co-transporter-1 and 2 (SGLT1/2) inhibitor with selectivity towards SGLT2. Previous studies showed that SGLT2 inhibitors can improve cardiac function and reduce myocardial infarction size in animal models of myocardial infarction (MI). However, it remains unknown whether the dual inhibition of SGLT1/2 by sotagliflozin has beneficial effects in this context. In this study, we investigated the potential cardioprotective effects of sotagliflozin in an animal model of MI. Sprague Dawley (SD) rats underwent left anterior descending coronary artery ligation or sham ligation then were randomly assigned to receive either sotagliflozin (10 mg/kg) or vehicle via intraperitoneal injection. Fourteen days post-MI, we assessed cardiac function using echocardiography and evaluated histological and molecular markers of cardiac remodeling and inflammation in the left ventricle. Our findings indicate that sotagliflozin treatment resulted in improved cardiac function and reduced infarct size compared with the vehicle-treated group. Additionally, sotagliflozin improved cardiac remodeling as shown by the decreased cardiac hypertrophy and cardiac apoptosis in the post-MI heart. Mechanistically, an apparent reduction in the cardiac inflammatory response in sotagliflozin-treated hearts was observed in the post-MI rats. Overall, our results suggest that sotagliflozin may have cardioprotective effects against myocardial infarction.