Sociological determinants of adherence to continuous positive airway pressure in the management of sleep apnoea syndrome: protocol for a transdisciplinary, prospective observational study.

INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is a chronic multiorgan pathology that has a negative impact on quality of life. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. However, CPAP termination rates remain very high, and adherence to therapy is a major issue. To date, studies targeting predictive factors of CPAP adherence by OSAS patients mainly include clinical data. The social, socioeconomic, psychological, and home environment aspects have been far less studied and largely underestimated. This study aims to obtain solid quantitative results examining the relationship between the determinants of refusal, non-adherence, or termination of CPAP treatment, and in particular the pivotal role played by health literacy. METHODS AND ANALYSIS: This is a prospective, multicentre, observational study recruiting patients attending the sleep clinic of the Grenoble Alpes University Hospital, France. Consecutive adults (>18 years) recently diagnosed with OSAS and prescribed CPAP treatment with telemonitoring will be enrolled in the present study. They will benefit from home visits by a CPAP technician or nurse at CPAP initiation. Patients will then be followed up for 6 months through the telemonitoring platform of a home-care provider. The primary objective is to evaluate the impact of health literacy (health literacy, measured by the European Health Literacy Survey questionnaire (HLS-EU-16) on the refusal, non-adherence or termination of CPAP treatment in newly diagnosed OSAS patients, during the first 6 months after diagnosis. The target sample size is 250 participants. ETHICS AND DISSEMINATION: The study protocol, patient information, and the non-opposition form were approved by the French national ethics committee (CPP 2021-92, January 2022). All patients are required to have signed a written informed consent form permitting their anonymised personal and medical data to be used for clinical research purposes. We will publish the results in a peer-reviewed medical journal and on our institutional websites. TRIAL REGISTRATION NUMBER: NCT05385302.

Dietary selenium intake influences Cx43 dephosphorylation, TNF-α expression and cardiac remodeling after reperfused infarction.

SCOPE: Post-infarct left ventricular dysfunction and cardiac remodeling are the primary causes of chronic heart failure in industrialized countries. In the present study, we examined the influence of dietary selenium intake on cardiac remodeling after reperfused myocardial infarction and explored one of the possible mechanisms. METHODS AND RESULTS: Rats were fed a diet containing either 0.05 mg/kg (Low-Se, group of rats receiving the low-selenium diet) or 1.50 mg/kg (group of rats receiving the high-selenium diet) selenium. At the end of the 5th week of the diet, rats were subjected to transient (1 h) coronary ligation followed by 8 days of reperfusion. Infarct size and cardiac passive compliance were increased in the Low-Se group compared with group of rats receiving the high-selenium diet. Similarly, indices of cardiac remodeling (thinning index and expansion index) were more altered in Low-Se hearts. These adverse effects of the Low-Se diet on cardiac remodeling were accompanied by an increase in cardiac TNF-α content, a decreased activity of antioxidant seleno-enzymes and an increase in connexin-43 dephosphorylation. CONCLUSION: Dietary selenium intake influences post-infarct cardiac remodeling even when provided within the range of physiological values. Our data suggest that the cardioprotective effect of selenium might be mediated by a reduced oxidative stress, a lower connexin-43 dephosphorylation, and a decreased TNF-α expression.

Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling.

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.

Selenium status as determinant of connexin-43 dephosphorylation in ex vivo ischemic/reperfused rat myocardium.

Recent studies have demonstrated that electrical uncoupling at gap junctions during ischemia is associated with cardiac Connexin-43 (Cx43) dephosphorylation. Whether oxidative stress is involved in this phenomenon still remains unclear. In the present study, we examined the influence of selenium intake on reperfusion-induced Cx43 dephosphorylation. Male Wistar rats were fed a diet containing either 0.05 mg/kg (Low-Se, n = 13) or 1.5 mg/kg (High-Se, n = 11) selenium for 8 weeks. At the end of this diet, hearts were isolated and subjected to 10 min regional ischemia followed by 10 min reperfusion. The level of dephosphorylated Cx43 was determined in tissue samples from ischemic/reperfused and non-ischemic regions of the hearts. At the end of the experiemental diet, the activity of the antioxidant enzyme glutathione peroxidase (GSH-Px) was increased in high-Se hearts compared with low-Se hearts (+ 13%; p < 0.05). After ischemia/reperfusion, in low-Se hearts, Cx43 dephosphorylation appeared significantly increased in the left ventricle compared to the non-ischemic right ventricle (+ 149%; p < 0.05). The high-Se diet significantly reduced Cx43 dephosphorylation in the left ventricle (p < 0.05 vs. low-Se diet). In conclusion, our results suggest that oxidative stress may be involved in Cx43 dephosphorylation during myocardial ischemia/reperfusion, thereby contributing to arrhythmogenesis.

Heme oxygenase-1-related carbon monoxide and flavonoids in ischemic/reperfused rat retina.

PURPOSE: There is increasing evidence to show cytoprotective effects of various flavonoid-rich extracts and the tissue-protective capacity of flavonoid-rich extract of sour cherry is due to flavonoid components of seeds. Sour cherry seed flavonoids were evaluated for their contribution to postischemic recovery related to endogenous carbon monoxide (CO) production in rat retinas subjected to ischemia/reperfusion. METHODS: Rats were orally treated with selected doses of flavonoid-rich extract of sour cherry seeds for 2 weeks. Animals were anesthetized, and a suture was placed behind the globe including the central retinal artery. Next, retinas were subjected to 90 minutes of ischemia followed by 24 hours of reperfusion. After this procedure, heme oxygenase-1 (HO-1)-related protein expression and enzyme activity, HO-1-related endogenous CO production, and ionic imbalance including tissue Na(+), K(+), and Ca(2+) in untreated and treated ischemic/reperfused retinas were measured. RESULTS: Retinal ischemia/reperfusion resulted in a significant reduction (to 10%) in HO-1 protein expression, enzyme activity, and HO-1-related endogenous CO production in the retina. These changes were accompanied by increases in retinal Na(+) and Ca(2+) gains and loss of K(+). In rats treated with 10 and 30 mg/kg of sour cherry flavonoid-rich extract, after 24 hours of reperfusion, tissue Na(+) and Ca(2+) accumulation and K(+) loss were prevented in comparison with the drug-free control. CONCLUSIONS: Sour cherry seed flavonoid-rich extract showed a protective effect against reperfusion-induced injury through its ability to reduce the changes in concentrations of retinal ions through HO-1-related endogenous CO production in the ischemic/reperfused retina.

Cardioprotective effect of chronic low dose ethanol drinking: insights into the concept of ethanol preconditioning.

The reason why low-to-moderate alcohol drinking is associated with reduced cardiovascular mortality is not elucidated. While data suggested that ethanol drinking may have a protective effect on global cardiac ischemia, the effect of chronic low dose ethanol drinking (CLEthD) on myocardial infarct size has not been evaluated in a model of regional ischemia. Using an isolated rat heart model to exclude the effect of various in vivo confounders, we have studied the effect of CLEthD on infarct size (IS) and left ventricular function after 30 min of regional ischemia and 120 min of reperfusion. The effect of CLEthD was compared with ischemic preconditioning (IPC) and protein kinase C (PKC) isoforms were analysed in the myocardium before the 30-min ischemia. Ethanol-fed rats received 9% (v/v) ethanol in their drinking water for 7 weeks. Four groups of rats were studied: (1) control, (2) ethanol, (3) control + IPC, (4) ethanol + IPC. Compared with controls (59 +/- 10), IS (as percent of risk zone) was smaller in the ethanol (39 +/- 6) and IPC (31 +/- 8) groups (both p < 0.05). Combination of ethanol and IPC in the same rats further decreased IS (-46% vs. ethanol, p < 0.05). PKC analyses did not show sustained isoform translocation in that model. These data indicate that chronic low dose ethanol drinking actually induces in the rat heart a chronic protective state that is independent from an effect on the traditional (lipid and coagulation) risk factors. Further studies are required to elucidate the mechanisms of that protection.

Ethanol, wine, and experimental cardioprotection in ischemia/reperfusion: role of the prooxidant/antioxidant balance.

It is now well established that oxidative stress resulting from reactive oxygen species (ROS) that are generated in cardiac myocytes subjected to ischemia/reperfusion plays a causative role in the development of heart failure and may contribute to promote cell death. During the last decade, several groups have reported that, in animal models of myocardial ischemia/reperfusion, certain nutrients, including ethanol and nonethanolic components of wine, may have a specific protective effect on the myocardium, independent of the classical risk factors implicated in vascular atherosclerosis and thrombosis. Mechanisms through which the consumption of alcoholic beverages protects against ischemia-induced cardiac injury are still unknown. One major open question is whether ethanol and nonethanolic components of wine are cardioprotective, at least in part, by interfering with the myocardial prooxidant/antioxidant balance. Important concepts, such as cardiac preconditioning, are now entering the field of nutrition, and recent experimental evidence suggests that ethanol and/or nonethanolic components of wine might exert preconditioning effects in animal models of myocardial ischemia/reperfusion. There is no doubt that such an observation, if confirmed in human subjects, might open new perspectives in the prevention and treatment of ischemic coronary heart disease.