In vivo measurements of atrial repolarization alternans based on standard pacemaker technology

It has been shown that repolarization alternans, a beat-to-beat alternation in action potential duration, enhances dispersion of repolarization above a critical heart rate and promotes susceptibility to ventricular arrhythmias. It is unknown whether repolarization alternans is measurable in the atria using standard pacemakers and whether it plays a role in promoting atrial fibrillation. In this work, atrial repolarization alternans amplitude and periodicity are studied in a sheep model of pacing-induced atrial fibrillation. Two pacemakers, each with one right atrial and ventricular lead, were implanted in 4 male sheep after ablation of the atrioventricular junction. The first one was used to deliver rapid pacing for measurements of right atrial repolarization alternans and the second one to record a unipolar electrogram. Atrial repolarization alternans appeared rate-dependent and its amplitude increased as a function of pacing rate. Repolarization alternans was intermittent but no periodicity was detected. An increase of repolarization alternans preceding episodes of non-sustained atrial fibrillation suggests that repolarization alternans is a promising parameter for assessment of atrial fibrillation susceptibility

Intermittent atrial tachycardia facilitates atrial fibrillation by a shortening of activation recovery interval

Introduction: We recently observed in a chronic ovine model that a shortening of action potential duration (APD) as assessed by the activation recovery interval (ARI) may be a mechanism whereby pacing-induced atrial tachycardia (PIAT) facilitates atrial fibrillation (AF), mediated by a return to 1:1 atrial capture after the effective refractory period has been reached. The aim of the present study is to evaluate the effect of long term intermittent burst pacing on ARI before induction of AF.Methods: We specifically developed a chronic ovine model of PIAT using two pacemakers (PM) each with a right atrial (RA) lead separated by ∼2cm. The 1st PM (Vitatron T70) was used to record a broadband unipolar RA EGM (800 Hz, 0.4 Hz high pass filter). The 2nd was used to deliver PIAT during electrophysiological protocols at decremental pacing CL (400 beats, from 400 to 110ms) and long term intermittent RA burst pacing to promote electrical remodeling (5s of burst followed by 2s of sinus rhythm) until onset of sustained AF. ARI was defined as the time difference between the peak of the atrial repolarization wave and the first atrial depolarization. The mean ARIs of paired sequences (before and after remodeling), each consisting of 20 beats were compared.Results: As shown in the figure, ARIs (n=4 sheep, 46 recordings) decreased post remodeling compared to baseline (86±19 vs 103±12 ms, p<0.05). There was no difference in atrial structure as assessed by light microscopy between control and remodeled sheep.Conclusions: Using standard pacemaker technology, atrial ARIs as a surrogate of APDs were successfully measured in vivo during the electrical remodeling process leading to AF. The facilitation of AF by PIAT mimicking salvos from pulmonary veins is heralded by a significant shortening of ARI

Association between physical activity, weight loss, anxiety, and lumbopelvic pain in postpartum women

Objective Lumbopelvic pain (LBPP) affects 45% to 81% of pregnant women, and 25% to 43% of these women report persistent LBPP beyond 3 months after giving birth. The objective of this study was to investigate the association of physical activity, weight status, anxiety, and evolution of LBPP symptoms in postpartum women. Methods This was a prospective observational cohort study with 3 time-point assessments: baseline (T0), 3 months (T3), and 6 months (T6). Women with persistent LBPP 3 to 12 months after delivery were recruited. At each time point, pain disability was assessed with the Pelvic Girdle Questionnaire and the Oswestry Disability Index (ODI), physical activity with Fitbit Flex monitors, and anxiety with the French-Canadian version of the State-Trait Anxiety Inventory. Weight was recorded using a standardized method. Pain intensity (numerical rating scale, 0-100) and frequency were assessed using a standardized text message on a weekly basis throughout the study. Results Thirty-two women were included (time postpartum: 6.6 ± 2.0 months; maternal age: 28.3 ± 3.8 years; body weight: 72.9 ± 19.1 kg), and 27 completed the T6 follow-up. Disability, pain intensity, and pain frequency improved at T6 (P < .001). Participants lost a mean of 1.9 ± 4.5 kg at T6, and this weight loss was correlated with reduction in LBPP intensity (r = 0.479, P = .011) and LBPP frequency (r = 0.386, P = .047), Pelvic Girdle Questionnaire score (r = 0.554, P = .003), and ODI score (r = 0.494, P = .009). Improvement in ODI score at T6 was correlated with the number of inactive minutes at T3 (r = −0.453, P = .026) and T6 (r = −0.457, P = .019), and with daily steps at T6 (r = 0.512, P = .006). Conclusion Weight loss is associated with positive LBPP symptom evolution beyond 3 months postpartum, and physical activity is associated with reduction in pain disability

Effects of a motor control exercise program on lumbopelvic pain recurrences and intensity in pregnant women with a history of lumbopelvic pain: A study protocol for a randomized controlled feasibility trial

Background About 50% of women experience lumbopelvic pain (LBPP) during their pregnancy. LBPP has negative repercussions on sleep, social and sexual life, physical and work capacity, and psychological health and contributes to physical inactivity. The benefits of LBPP prevention or treatment in pregnant women through specific exercises should therefore be further investigated. This study protocol has been designed to establish the feasibility of implementing motor control exercise program with pregnant women presenting with a history of LBPP. Methods/design Forty pregnant women with a history of LBPP will be recruited and randomly allocated to a control (20 participants) or intervention (20 participants) group. The control group will receive standard prenatal care, including basic information on what to do when suffering from LBPP. The intervention group will participate in three 40-min exercise sessions per week from < 20 weeks until 34–36 weeks of gestation: one supervised group session via the Zoom platform (once a month, this session will take place at the Université du Québec à Trois-Rivières) and two unsupervised sessions at home. A motor control exercise program will be developed to target strengthening of the lumbo-pelvic-hip core muscles and improve spinal and pelvic stabilization. Participants of this group will also receive standard prenatal care. Women of the control group will receive after 6 weeks postpartum an exercise program designed to reduce LBPP they may have developed during pregnancy and that may persist after delivery. Primary outcomes will be participants’ recruitment, retention and adherence rates, safety, and acceptability of the intervention. Secondary outcomes will include LBPP incidence, frequency, and intensity, as well as self-reported functional disability, physical activity levels, fear avoidance behavior, anxiety, and depression. Discussion This study will inform the feasibility of conducting a full-scale randomized controlled study to test the effectiveness of a motor control exercise program on the prevention and treatment of LBPP in women with a history of LBPP. Adequate prevention and treatment of pregnant women with a history of LBPP should help limit the recurrences of LBPP or the aggravation of its intensity during pregnancy. Trial registration US National Institutes of Health Clinical Trials registry NCT04253717 April 27, 2021

Mechanisms underlying lumbopelvic pain during pregnancy: A proposed model

Up to 86% of pregnant women will have lumbopelvic pain during the 3rd trimester of pregnancy and women with lumbopelvic pain experience lower health-related quality of life during pregnancy than women without lumbopelvic pain. Several risk factors for pregnancy-related lumbopelvic pain have been identified and include history of low back pain, previous trauma to the back or pelvis and previous pregnancy-related pelvic girdle pain. During pregnancy, women go through several hormonal and biomechanical changes as well as neuromuscular adaptations which could explain the development of lumbopelvic pain, but this remains unclear. The aim of this article is to review the potential pregnancy-related changes and adaptations (hormonal, biomechanical and neuromuscular) that may play a role in the development of lumbopelvic pain during pregnancy. This narrative review presents different mechanisms that may explain the development of lumbopelvic pain in pregnant women. A hypotheses-driven model on how these various physiological changes potentially interact in the development of lumbopelvic pain in pregnant women is also presented. Pregnancy-related hormonal changes, characterized by an increase in relaxin, estrogen and progesterone levels, are potentially linked to ligament hyperlaxity and joint instability, thus contributing to lumbopelvic pain. In addition, biomechanical changes induced by the growing fetus, can modify posture, load sharing and mechanical stress in the lumbar and pelvic structures. Finally, neuromuscular adaptations during pregnancy include an increase in the activation of lumbopelvic muscles and a decrease in endurance of the pelvic floor muscles. Whether or not a causal link between these changes and lumbopelvic pain exists remains to be determined. This model provides a better understanding of the mechanisms behind the development of lumbopelvic pain during pregnancy to guide future research. It should allow clinicians and researchers to consider the multifactorial nature of lumbopelvic pain while taking into account the various changes and adaptations during pregnancy

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (−60–75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum

Gut microbiota and diabetes: from pathogenesis to therapeutic perspective

More than several hundreds of millions of people will be diabetic and obese over the next decades in front of which the actual therapeutic approaches aim at treating the consequences rather than causes of the impaired metabolism. This strategy is not efficient and new paradigms should be found. The wide analysis of the genome cannot predict or explain more than 10–20% of the disease, whereas changes in feeding and social behavior have certainly a major impact. However, the molecular mechanisms linking environmental factors and genetic susceptibility were so far not envisioned until the recent discovery of a hidden source of genomic diversity, i.e., the metagenome. More than 3 million genes from several hundreds of species constitute our intestinal microbiome. First key experiments have demonstrated that this biome can by itself transfer metabolic disease. The mechanisms are unknown but could be involved in the modulation of energy harvesting capacity by the host as well as the low-grade inflammation and the corresponding immune response on adipose tissue plasticity, hepatic steatosis, insulin resistance and even the secondary cardiovascular events. Secreted bacterial factors reach the circulating blood, and even full bacteria from intestinal microbiota can reach tissues where inflammation is triggered. The last 5 years have demonstrated that intestinal microbiota, at its molecular level, is a causal factor early in the development of the diseases. Nonetheless, much more need to be uncovered in order to identify first, new predictive biomarkers so that preventive strategies based on pre- and probiotics, and second, new therapeutic strategies against the cause rather than the consequence of hyperglycemia and body weight gain