Mesenchymal stromal cell (MSC)-based cell therapy in acute respiratory diseases is based on MSC secretion of paracrine factors. Several strategies have proposed to improve this are being explored ...including pre-conditioning the MSCs prior to administration. We here propose a strategy for improving the therapeutic efficacy of MSCs based on cell preconditioning by growing them in native extracellular matrix (ECM) derived from the lung. To this end, a bioink with tunable stiffness based on decellularized porcine lung ECM hydrogels was developed and characterized. The bioink was suitable for 3D culturing of lung-resident MSCs without the need for additional chemical or physical crosslinking. MSCs showed good viability, and contraction assays showed the existence of cell–matrix interactions in the bioprinted scaffolds. Adhesion capacity and length of the focal adhesions formed were increased for the cells cultured within the lung hydrogel scaffolds. Also, there was more than a 20-fold increase of the expression of the CXCR4 receptor in the 3D-cultured cells compared to the cells cultured in plastic. Secretion of cytokines when cultured in an in vitro model of lung injury showed a decreased secretion of pro-inflammatory mediators for the cells cultured in the 3D scaffolds. Moreover, the morphology of the harvested cells was markedly different with respect to conventionally (2D) cultured MSCs. In conclusion, the developed bioink can be used to bioprint structures aimed to improve preconditioning MSCs for therapeutic purposes.
Heart failure (HF) impairs diaphragm function. Animal models realistically mimicking HF should feature both the cardiac alterations and the diaphragmatic dysfunction characterizing this disease. The ...isoproterenol-induced HF model is widely used, but whether it presents diaphragmatic dysfunction is unknown. However, indirect data from research in other fields suggest that isoproterenol could increase diaphragm function. The aim of this study was to test the hypothesis that the widespread rodent model of isoproterenol-induced HF results in increased diaphragmatic contractility. Forty C57BL/6J male mice were randomized into 2 groups: HF and healthy controls. After 30 days of isoproterenol infusion to establish HF, in vivo diaphragmatic excursion and ex vivo isolated diaphragm contractibility were measured. As compared with healthy controls, mice with isoproterenol-induced HF showed the expected changes in structural and functional echocardiographic parameters and lung edema. isoproterenol-induced HF increased in vivo diaphragm excursion (by ≈30%, p<0.01) and increased by ≈50% both ex vivo peak specific force (p<0.05) and tetanic force (p<0.05) at almost all 10–100 Hz frequencies (p<0.05), with reduced fatigue resistance (p<0.01) when compared with healthy controls. Expression of myosin genes encoding the main muscle fiber types revealed that Myh4 was higher in isoproterenol-induced HF than in healthy controls (p<0.05), suggesting greater distribution of type IIb fibers. These results show that the conventional isoproterenol-induced HF model increases diaphragm contraction, a finding contrary to what is observed in patients with HF. Therefore, this specific model seems limited for translational an integrative HF research, especially when cardio-respiratory interactions are investigated.
Exercise training (ET) is a critical component of cardiac rehabilitation (CR), but it remains underused. The aim of this study was to compare clinical outcomes between patients who completed ET ...(A-T), those who accepted ET but did not complete it (A-NT), and those who did not accept to undergo it (R-NT), and to analyze reasons for rejecting or not completing ET.
A unicenter ambispective observational registry study of 497 patients with acute coronary syndrome (ACS) was carried out in Barcelona, Spain, from 2016 to 2019. The primary endpoint was a composite of all-cause mortality, hospitalization for ACS, or need for revascularization during follow-up. Multivariable analysis was carried out to identify variables independently associated with the primary outcome. Initially, 70% of patients accepted participating in the ET, but only 50.5% completed it. The A-T group were younger and had fewer comorbidities. Baseline characteristics in A-NT and R-NT groups were very similar. The main reason for not undergoing or completing ET was rejection (reason unknown) or work/schedule incompatibility. The median follow-up period was 31 months. Both the composite primary endpoint and mortality were significantly lower in the A-T group compared to the A-NT and R-NT (primary endpoint: 3.6% vs. 23.2% vs. 20.4%,
< 0.001, respectively; mortality: 0.8% vs. 9.1% vs. 8.2%,
< 0.001; respectively). During multivariable analysis, the only variables that remained statistically significant with the composite endpoint were ET completion, previous ACS, and anemia.
Completion of ET after ACS was associated with improved prognosis. Only half of the patients completed the ET program, with the leading reasons for not completing it being refusal (reason unknown) and work/schedule incompatibility. These results highlight the need to focus on the needs of patients in order to guarantee that structural barriers to ET no longer exist.
Obstructive sleep apnea (OSA) has been associated with heart failure (HF). Sleep fragmentation (SF), one of the main hallmarks of OSA, induces systemic inflammation, oxidative stress and sympathetic ...activation, hence potentially participating in OSA-induced cardiovascular consequences. However, whether SF
is deleterious to heart function is unknown. The aim of this study was to non-invasively evaluate the effect of SF mimicking OSA on heart function in healthy mice and in mice with HF.
Forty C57BL/6J male mice were randomized into 4 groups: control sleep (C), sleep fragmentation (SF), isoproterenol-induced heart failure (HF), and mice subjected to both SF+HF. Echocardiography was performed at baseline and after 30 days to evaluate left ventricular end-diastolic (LVEDD) and end-systolic (LVESD) diameters, left ventricular ejection fraction (LVEF) and fraction shortening (FS). The effects of SF and HF on these parameters were assessed by two-way ANOVA. Mice with isoproterenol-induced HF had significant increases in LVEDD and LVESD, as well as a decreases in LVEF and FS (
= 0.013,
= 0.006,
= 0.027, and
= 0.047, respectively). However, no significant effects emerged with SF (
= 0.480,
= 0.542,
= 0.188, and
= 0.289, respectively).
Chronic SF mimicking OSA did not induce echocardiographic changes in cardiac structure and function in both healthy and HF mice. Thus, the deleterious cardiac consequences of OSA are likely induced by other perturbations associated with this prevalent condition, or result from interactions with underlying comorbidities in OSA patients.
Cabrera-Aguilera, Ignacio, David Rizo-Roca, Elisa A. Marques, Garoa Santocildes, Teresa Pagès, Gines Viscor, António A. Ascensão, José Magalhães, and Joan Ramon Torrella. Additive effects of ...intermittent hypobaric hypoxia and endurance training on bodyweight, food intake, and oxygen consumption in rats. High Alt Med Biol. 19:278-285, 2018.-We used an animal model to elucidate the effects of an intermittent hypobaric hypoxia (IHH) and endurance exercise training (EET) protocol on bodyweight (BW), food and water intake, and oxygen consumption. Twenty-eight young adult male rats were divided into four groups: normoxic sedentary (NS), normoxic exercised (NE), hypoxic sedentary (HS), and hypoxic exercised (HE). Normoxic groups were maintained at an atmospheric pressure equivalent to sea level, whereas the IHH protocol consisted of 5 hours per day for 33 days at a simulated altitude of 6000 m. Exercised groups ran in normobaric conditions on a treadmill for 1 hour/day for 5 weeks at a speed of 25 m/min. At the end of the protocol, both hypoxic groups showed significant decreases in BW from the ninth day of exposure, reaching final 10% (HS) to 14.5% (HE) differences when compared with NS. NE rats also showed a significant weight reduction after the 19th day, with a decrease of 7.4%. The BW of hypoxic animals was related to significant hypophagia elicited by IHH exposure (from 8% to 12%). In contrast, EET had no effect on food ingestion. Total water intake was not affected by hypoxia but was significantly increased by exercise. An analysis of oxygen consumption at rest (mL O
/kg·min) revealed two findings: a significant decrease in both hypoxic groups after the protocol (HS, 21.7 ± 0.70 vs. 19.1 ± 0.78 and HE, 22.8 ± 0.80 vs. 17.1 ± 0.90) and a significant difference at the end of the protocol between NE (21.3 ± 0.77) and HE (17.1 ± 0.90). These results demonstrate that IHH and EET had an additive effect on BW loss, providing evidence that rats underwent a metabolic adaptation through a reduction in oxygen consumption measured under normoxic conditions. These data suggest that the combination of IHH and EET could serve as an alternative treatment for the management of overweight and obesity.
Several risk scores have been used to predict risk after an acute coronary syndrome (ACS), but none of these risk scores include functional class. The aim was to assess the predictive value of risk ...stratification (RS), including functional class, and how cardiac rehabilitation (CR) changed RS. Two hundred and thirty-eight patients with ACS from an ambispective observational registry were stratified as low (L) and no-low (NL) risk and classified according to exercise compliance; low risk and exercise (L-E), low risk and control (no exercise) (L-C), no-low risk and exercise (NL-E), and no-low risk and control (NL-C). The primary endpoint was cardiac rehospitalization. Multivariable analysis was performed to identify variables independently associated with the primary endpoint. The L group included 56.7% of patients. The primary endpoint was higher in the NL group (18.4% vs. 4.4%, p < 0.001). After adjustment for age, sex, diabetes, and exercise in multivariable analysis, HR (95% CI) was 3.83 (1.51−9.68) for cardiac rehospitalization. For RS and exercise, the prognosis varied: the L-E group had a cardiac rehospitalization rate of 2.5% compared to 26.1% in the NL-C group (p < 0.001). Completing exercise training was associated with reclassification to low-risk, associated with a better outcome. This easy-to-calculate risk score offers robust prognostic information. No-exercise groups were independently associated with the worst outcomes. Exercise-based CR program changed RS, improving classification and prognosis.
Obstructive sleep apnoea (OSA) constitutes a public health problem, with various systemic consequences that can increase cardiovascular morbidity and mortality as well as increase healthcare ...expenditure. This review discusses the rationale and effects of using general physical exercise, oropharyngeal exercises, and respiratory muscle training as an adjunctive treatment for patients with sleep apnoea. The recommended treatment for OSA is the use of continuous positive airway pressure, which is a therapy that prevents apnoea events by keeping the airways open. In the last decade, coadjuvant treatments that aim to support weight loss (including diet and physical exercise) and oropharyngeal exercises have been proposed to lower the apnoea/hypopnoea index among patients with OSA. Based on the available evidence, health professionals could decide to incorporate these therapeutic strategies to manage patients with sleep apnoea.
Aims
Despite the evidence, lipid-lowering treatment (LLT) in secondary prevention remains insufficient, and a low percentage of patients achieve the recommended LDL cholesterol (LDLc) levels by the ...guidelines. We aimed to evaluate the efficacy of an intensive, mobile devices-based healthcare lipid-lowering intervention after hospital discharge in patients hospitalized for acute coronary syndrome (ACS).
Methods and results
Ambiespective register in which a mobile devices-based healthcare intervention including periodic follow-up, serial lipid level controls, and optimization of lipid-lowering therapy, if appropriate, was assessed in terms of serum lipid-level control at 12 weeks after discharge. A total of 497 patients, of which 462 (93%) correctly adhered to the optimization protocol, were included in the analysis. At the end of the optimization period, 327 (70.7%) patients had LDLc levels ≤ 70 mg/dL. 40% of patients in the LDLc ≤ 70 mg/dL group were upgraded to very-high intensity lipid-lowering ability therapy vs. 60.7% in the LDLc > 70 mg/dL group,
p
< 0.001. Overall, 38.5% of patients had at least a change in their LLT. Side effects were relatively infrequent (10.7%). At 1-year follow-up, LDLc levels were measured by the primary care physician in 342 (68.8%) of the whole cohort of 497 patients. In this group, 71.1% of patients had LDLc levels ≤ 70 mg/dL.
Conclusion
An intensive, structured, mobile devices-based healthcare intervention after an ACS is associated with more than 70% of patients reaching the LDLc levels recommended by the clinical guidelines. In patients with LDLc measured at 1-year follow-up, 71.1% had LDLc levels ≤ 70 mg/dL.
Heart failure (HF) is a common condition associated with a high rate of hospitalizations and adverse outcomes. HF is characterized by impairments of either the cardiac ventricular filling, ejection ...of blood capacity or both. Sleep fragmentation (SF) involves a series of short sleep interruptions that lead to fatigue and contribute to cognitive impairments and dementia. Both conditions are known to be associated with increased inflammation and dysbiosis of the gut microbiota. In the present study, mice were distributed into four groups, and subjected for four weeks to either HF, SF, both HF and SF, or left unperturbed as controls. We used 16S metabarcoding to assess fecal microbiome composition before and after the experiments. Evidence for distinct alterations in several bacterial groups and an overall decrease in alpha diversity emerged in HF and SF treatment groups. Combined HF and SF conditions, however, showed no synergism, and observed changes were not always additive, suggesting preliminarily that some of the individual effects of either HF or SF cancel each other out when applied concomitantly.
Although measures of exercise performance and physical activity are known to be related to 6-minute walk test (6mWT), the role of the strength of each muscle group of the lower limb in the locomotor ...capacity during the development period is unknown.
To identify the role of the isometric strength of lower limb muscles and cardiovascular parameters on the locomotor capacity in children and adolescents, controlling for participants sex, age, and height.
Participants (7 to 15 years old; female, n= 113; male, n= 128) were assessed for isometric strength (seven lower limb muscles), cardiovascular parameters (diastolic pressure, oxygen saturation, resting heart rate, respiratory rate), and 6mWT. Participants were split into nine age groups and separated by 1-year intervals.
Hip flexors-controlled for sex, age, and height-explained a meaningful percentage of the variance (R=2 0.45; p< 0.001) for 6mWT distance, and the resting heart rate explained a change in R2 of only 2% (p= 0.008).
Isometric strength of hip flexors explained ∼ 50% of the 6mWT distance, suggesting the importance of strength from an early age. Other factors, such as cardiovascular parameters, while relevant, may exert a secondary role on youth's capacity.
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