The prophylactic and therapeutic effects of cannabidiol on lung injury secondary to cardiac ischemia model in rats via PERK/NRF2/CHOP/BCL2 pathway.

BACKGROUND: Inflammation and oxidative stress are key players in lung injury stemming from cardiac ischemia (LISCI). Cannabidiol (CBD) demonstrates tissue-protective properties through its antioxidant, anti-inflammatory, and anti-apoptotic characteristics. This study aims to assess the preventive (p-CBD) and therapeutic (t-CBD) effects of CBD on LISCI. METHODS: Forty male Wistar Albino rats were divided into four groups: control (CON), LISCI, p-CBD, and t-CBD. The left anterior descending coronary artery was ligated for 30 min of ischemia followed by 30 min of reperfusion. Lung tissues were then extracted for histopathological, immunohistochemical, genetic, and biochemical analyses. RESULTS: Histopathologically, marked hyperemia, increased septal tissue thickness, and inflammatory cell infiltrations were observed in the lung tissues of the LISCI group. Spectrophotometrically, total oxidant status and oxidative stress index levels were elevated, while total antioxidant status levels were decreased. Immunohistochemically, expressions of cyclooxygenase-1 (COX1), granulocyte colony-stimulating factor (GCSF), interleukin-6 (IL6) were increased. In genetic analyses, PERK and CHOP expressions were increased, whereas Nuclear factor erythroid 2-related factor 2 (NRF2) and B-cell leukemia/lymphoma 2 protein (BCL2) expressions were decreased. These parameters were alleviated by both prophylactic and therapeutic CBD treatment protocols. CONCLUSION: In LISCI-induced damage, both endoplasmic reticulum and mitochondrial stress, along with oxidative and inflammatory markers, were triggered, resulting in lung cell damage. However, both p-CBD and t-CBD treatments effectively reversed these mechanisms, normalizing all histopathological, biochemical, and PCR parameters.

The benefits of GLP-1 drugs beyond obesity.

Glucagon-like peptide-1-based medicines have weight loss-independent actions.

Role of arachidonic acid in ischemic heart disease under different comorbidities: risk or protection?

In a translational study involving animal models and human subjects, Lv et al. demonstrate that arachidonic acid (AA) exhibits cardioprotective effects in diabetic myocardial ischemia, suggesting a departure from its known role in promoting ferroptosis-a form of cell death characterized by iron-dependent lipid peroxidation. However, the study does not address how underlying diabetic conditions might influence the metabolic pathways of AA, which are critical for fully understanding its impact on heart disease. Diabetes can significantly alter lipid metabolism, which in turn might affect the enzymatic processes involved in AA's metabolism, leading to different outcomes in the disease process. Further examination of the role of diabetes in modulating AA's effects could enhance the understanding of its protective mechanism in ischemic conditions. This could also lead to more targeted and effective therapeutic strategies for managing myocardial ischemia in diabetic patients, such as optimizing AA levels to prevent heart damage while avoiding exacerbating factors like ferroptosis.

Challenges and benefits of using the HeartDiet food frequency questionnaire in cardiac rehabilitation practice.

BACKGROUND AND AIMS: A heart-healthy diet is an important component of secondary prevention in ischemic heart disease. The Danish Health Authority recommends using the validated 19-item food frequency questionnaire HeartDiet in cardiac rehabilitation practice to assess patients' need for dietary interventions, and HeartDiet has been included in national electronic patient-reported outcome instruments for cardiac rehabilitation. This study aims to evaluate challenges and benefits of its use. The objectives are to: 1) describe HeartDiet responses of patients with ischemic heart disease and discuss HeartDiet's suitability as a screening tool, 2) discuss whether an abridged version should replace HeartDiet. METHODS AND RESULTS: A cross-sectional study using data from a national feasibility test. HeartDiet was sent electronically to 223 patients with ischemic heart disease prior to cardiac rehabilitation. Data were summarised with descriptive statistics, and Spearman's rank correlations, explorative factor analysis, and Cohen's kappa coefficient were used to derive and evaluate abridged versions. The response rate was 68 % (n = 151). Evaluated with HeartDiet, no respondents had a heart-healthy diet. There was substantial agreement between HeartDiet and an abridged 9-item version (kappa = 0.6926 for Fat Score, 0.6625 for FishFruitVegetable Score), but the abridged version omits information on milk products, wholegrain, nuts, and sugary snacks. CONCLUSION: With the predefined cut-offs, HeartDiet's suitability as a screening tool to assess needs for dietary interventions was limited, since no respondents were categorised as having a heart-healthy diet. An abridged version can replace HeartDiet, but the tool's educational potential will be compromised, since important items will be omitted.

Interrupting Effect of Social Distancing on Ischemic Heart Disease, Asthma, Stroke, and Suicide Attempt Patients by PM2.5 Exposure.

PURPOSE: This study aimed to examine the interrupting effect of social distancing (SD) on emergency department (ED) patients with ischemic heart disease (IHD), stroke, asthma, and suicide attempts by PM2.5 exposure in eight Korean megacities from 2017 to 2020. MATERIALS AND METHODS: The study used National Emergency Department Information System and AirKorea data. A total of 469014 patients visited EDs from 2017 to 2020. Interrupted time series analysis was employed to examine changes in the level and slope of the time series, relative risk, and confidence intervals (CIs) by PM2.5 exposure. The SD level was added to the sensitivity analysis. RESULTS: The interrupted time series analysis demonstrated a significant increase in the ratio of relative risk (RRR) of IHD patients in Seoul (RRR=1.004, 95% CI: 1.001, 1.006) and Busan (RRR=1.007, 95% CI: 1.002, 1.012) post-SD. Regarding stroke, only patients in Seoul exhibited a significant decrease post-SD (RRR=0.995, 95% CI: 0.991, 0.999). No significant changes were observed for asthma in any of the cities. In the case of suicide attempts, Ulsan demonstrated substantial pre-SD (RR=0.827, 95% CI: 0.732, 0.935) and post-SD (RRR=1.200, 95% CI: 1.057, 1.362) differences. CONCLUSION: While the interrupting effect of SD was not as pronounced as anticipated, this study did validate the effectiveness of SD in modifying health behaviors and minimizing avoidable visits to EDs in addition to curtailing the occurrence of infectious diseases.

Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury.

The gut microbiome has emerged as a potential target for the treatment of cardiovascular disease. Ischemia/reperfusion (I/R) after myocardial infarction is a serious complication and whether certain gut bacteria can serve as a treatment option remains unclear. Lactobacillus reuteri (L. reuteri) is a well-studied probiotic that can colonize mammals including humans with known cholesterol-lowering properties and anti-inflammatory effects. Here, the prophylactic cardioprotective effects of L. reuteri or its metabolite γ-aminobutyric acid (GABA) against acute ischemic cardiac injury caused by I/R surgery are demonstrated. The prophylactic gavage of L. reuteri or GABA confers cardioprotection mainly by suppressing cardiac inflammation upon I/R. Mechanistically, GABA gavage results in a decreased number of proinflammatory macrophages in I/R hearts and GABA gavage no longer confers any cardioprotection in I/R hearts upon the clearance of macrophages. In vitro studies with LPS-stimulated bone marrow-derived macrophages (BMDM) further reveal that GABA inhibits the polarization of macrophages toward the proinflammatory M1 phenotype by inhibiting lysosomal leakage and NLRP3 inflammasome activation. Together, this study demonstrates that the prophylactic oral administration of L. reuteri or its metabolite GABA attenuates macrophage-mediated cardiac inflammation and therefore alleviates cardiac dysfunction after I/R, thus providing a new prophylactic strategy to mitigate acute ischemic cardiac injury.

Positive effects of low-dose S-ketamine on preventing myocardial injury after thoracoscopic lobectomy in patients aged 70 to 85.

OBJECTIVE: To investigate the effects of low-dose S-ketamine on marker of myocardial injury (BNP, hs-cTnT and HFABP) after thoracoscopic lobectomy in patients aged 70 to 85. METHODS: One hundred patients (four cases excluded) aged 70-85 years, with body mass index 18-24 kg·m-2 and American Society of Anesthesiologists physical status II-III, scheduled for elective lobectomy from April 2022 to April 2023, were selected. The patients were divided into two groups by a random number table method, namely, the low-dose S-ketamine combined with GDFT group (group S) and the control group (group C), with 48 cases in each group. In group S, a low dose of S-ketamine (0.2 mg/kg) was given 1 min before intubation, and the maintenance dose was 0.12 mg·kg-1·h-1. Fluid therapy, guided by cardiac index (CI), changes in stroke volume (△SV), and other dynamic indicators, was used for rehydration during the operation. Group C was given the same amount of normal saline (0.2 mg/kg) 1 min before intubation, and the same rehydration therapy was adopted during the operation. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were observed and recorded immediately after entering the operating room (T0), immediately after intubation (T1), immediately after the beginning of one-lung ventilation (OLV) (T2), immediately after the beginning of surgery (T3), immediately after the end of OLV (T4), and at the end of surgery (T5). The intraoperative fluid intake and output and the use of vasoactive drugs were recorded. The plasma levels of heart-type fatty acid-binding protein (HFABP), high-sensitivity troponin T (hs-cTnT), brain natriuretic peptide (BNP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were recorded 24 h before operation and 24 and 48 h after operation. Visual analogue scale (VAS) pain scores at rest were recorded at 2 (V1), 6 (V2), 12 (V3), 24 (V4), and 48 h (V5) after operation, and the occurrence of myocardial ischemia during hospitalization was noted. RESULTS: Compared with group C, MAP was significantly higher at T1-T5 in group S (P < 0.05), and the plasma concentrations of IL-6, IL-8, TNF-α, BNP, hs-cTnT, and HFABP were significantly lower at 24 and 48 h after operation (P < 0.05). The VAS pain scores at 2, 6, 12, 24, and 48 h after operation, the number of effective patient-controlled intravenous analgesia (PCIA) compressions, and the total number of PCIA compressions within 48 h after operation were significantly decreased (P < 0.05). Compared with group C, The hospitalization days, and the incidence of postoperative myocardial ischemia in group S were lower (P < 0.05). There were no significant intergroup differences in urine volume, extubation time, the incidence of postoperative atrial fibrillation, bleeding volume, colloid infusion volume, total fluid infusion volume, and the incidence of rescue analgesia. CONCLUSIONS: Low-dose S-ketamine can reduce the levels of hs-cTnT, HFABP, and BNP in older patients after pulmonary lobectomy, which has a positive effect on preventing myocardial injury. TRIAL REGISTRATION: This study was registered on CHICTR (registration No. ChiCTR2300074475). Date of registration: 08/08/2023.

An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats.

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

A New Age for Secondary Prevention: Optimal Medical Therapy for Stable Ischemic Heart Disease Among Patients with Diabetes and/or Obesity.

Patients with type 2 diabetes and/or obesity and established cardiovascular disease are at increased risk for recurrent cardiovascular events. The indications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors have been expanded in the last decade due to benefit in cardiovascular outcome trials and are now considered guideline-recommended therapy for patients with type 2 diabetes and cardiovascular disease. Emerging data have begun to suggest that GLP-1RAs can decrease major adverse cardiovascular events among patients with obesity without diabetes. Overall, prescription of these agents remains low, despite being key to improve disparities in recurrent cardiovascular events. In this review, we discuss optimal medical therapy for secondary prevention for stable ischemic heart disease.

[Risk factor control, lifestyle intervention, and prescribed medication in a cohort of patients with ischemic heart disease]. / Control sobre factores de riesgo, intervención sobre estilos de vida, y medicación prescrita en una cohorte de pacientes con cardiopatía isquémica.

OBJECTIVE: The aim of this study was to analyze the recommended prevention measures in our health area for patients discharged after a myocardial infarction. METHODS: This was a retrospective descriptive study that selected patients with acute coronary syndrome in our health area in the previous calendar year. Control of the risk factors observed at the time of the coronary event and at 1 year and medication prescribed 1 year after the episode were studied. Variables including age, sex, control of dyslipidemia, hypertension or diabetes mellitus, adherence to treatment and lifestyle habits were analyzed. RESULTS: Risk factor control was insufficient and sometimes even unassessed at the time of infarction. Although a slight improvement was perceived, control remained insufficient 1 year later. Moreover, patients, particularly women, were undertreated: one fifth (20%) more men were receiving appropriate treatment than women year after the myocardial event. CONCLUSIONS: An additional effort must be made compared to what is currently being done, both by specialists in Hospital Care and Primary Care, to carry out good control of risk factors, meaning the control of certain diseases such as diabetes, high blood pressure or dyslipidemia, as well as habits or lifestyles that increase the probability of suffering a cardiovascular event. Furthermore, it is important to avoid these cardiovascular diseases and their relapse to reinforce adherence to the prescribed treatments.

Association of dietary fats with ischemic heart disease (IHD): a case-control study.

BACKGROUND: This study aimed to investigate the association between different types of dietary fats with ischemic heart disease (IHD). METHODS: This case-control study was conducted on 443 cases and 453 controls aged 40-80 years in Tehran, Iran. The semi-quantitative 237-item food frequency questionnaire (FFQ) was used to assess the amount of food intake. Nutritionist IV was applied to test the amount of consumption of dietary fats. RESULTS: The case group had a lower intake of docosahexaenoic acid (DHA) (11.36 ± 12.58 vs. 14.19 ± 19.57, P = 0.01) than the control group. A negative association was found between IHD and DHA (OR 0.98, CI 95% 0.97-0.99, P = 0.01). No significant association was observed between IHD with the intake of cholesterol, trans fatty acids (TFA), saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), eicosatetraenoic acid (EPA), and α-Linolenic acid (ALA). CONCLUSION: It was found that DHA may reduce the risk of IHD, whereas there was no significant association between other types of dietary fats with the odds of IHD. If the results of this study are confirmed in future research, a higher intake of DHA in diet can be recommended as a strategy to prevent IHD events.

Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease.

Ischemic heart disease is the greatest health burden and most frequent cause of death worldwide. Myocardial ischemia/reperfusion is the pathophysiological substrate of ischemic heart disease. Improvements in prevention and treatment of ischemic heart disease have reduced mortality in developed countries over the last decades, but further progress is now stagnant, and morbidity and mortality from ischemic heart disease in developing countries are increasing. Significant problems remain to be resolved and require a better pathophysiological understanding. The present review attempts to briefly summarize the state of the art in myocardial ischemia/reperfusion research, with a view on both its coronary vascular and myocardial aspects, and to define the cutting edges where further mechanistic knowledge is needed to facilitate translation to clinical practice.

PEG-modified nano liposomes co-deliver Apigenin and RAGE-siRNA to protect myocardial ischemia injury.

Ischemic heart disease (IHD) is a cardiac disorder in which myocardial damage occurs as a result of myocardial ischemia and hypoxia. Evidence suggests that oxidative stress and inflammatory responses are critical in the development of myocardial ischemia. Therefore, the combination of antioxidant and anti-inflammatory applications is an effective strategy to combat ischemic heart disease. In this paper, polyethylene glycol (PEG)-modified cationic liposomes were used as carriers to deliver apigenin (Apn) with small interfering RNA (siRNA) targeting the receptor for glycosylation end products (RAGE) (siRAGE) into cardiomyocytes to prevent myocardial ischemic injury through antioxidant and anti-inflammatory effects. Our results showed that we successfully prepared cationic PEG liposomes loaded with Apn and siRAGE (P-CLP-A/R) with normal appearance and morphology, particle size and Zeta potential, and good encapsulation rate, drug loading and in vitro release degree. In vitro, P-CLP-A/R was able to prevent oxidative stress injury in H9C2 cells, downregulate the expression of RAGE, reduce the secretion of cellular inflammatory factors and inhibit apoptosis through the RAGE/NF-κB pathway; In vivo, P-CLP-A/R was able to prevent arrhythmia and myocardial pathological injury, and reduce apoptosis and the area of necrotic myocardium in rats. In conclusion, P-CLP-A/R has a protective effect on myocardial ischemic injury and is expected to be a potential drug for the prevention of ischemic heart disease in the future.

PLGA nanoparticles enhanced cardio-protection of scutellarin and paeoniflorin against isoproterenol-induced myocardial ischemia in rats.

This study aims to examine the impact of the microfluidic preparation process on the quality of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-delivered with scutellarin (SCU) and paeoniflorin (PAE) in comparison to a conventional emulsification method and to evaluatethe potential cardio-protective effect of SCU-PAE PLGA NPs produced through emulsification method. As compared with microfluidics, the nanoparticles prepared by emulsification method exhibited a smaller size, higher encapsulation efficiency, higher drug loading and lower viscosity for injection. Subsequently, a rat myocardial ischemia (MI) was established using male Sprague-Dawley (SD) rats (250 ± 20 g) subcutaneously injected with 85 mg/kg isoproterenol (ISO) for two consecutive days. The pharmacokinetic findings demonstrated that our SCU-PAE PLGA NPs exhibited prolonged blood circulation time in MI rats, leading to increased levels of SCU and PAE in the heart. This resulted in significant improvements in electrocardiogram and cardiac index, as well as reduced serum levels of CK, LDH, AST. Histopathological analysis using H&E and TUNEL staining provided further evidence of improved cardiac function and decreased apoptosis. Additionally, experiments measuring SOD, MDA, GSH, NO, TNF-α and IL-6 levels indicated that SCU-PAE PLGA NPs may effectively treat MI through oxidative stress and inflammatory pathways, thereby establishing it as a promising therapeutic intervention.

Examining disparities in cardiovascular disease prevention strategies and incidence rates between urban and rural populations: insights from Kazakhstan.

Kazakhstan is experiencing a high burden of cardiovascular disease (CVD), and the country has implemented a range of strategies aimed at controlling CVD. The study aims to conduct a content analysis of the policies implemented in the country and augment it with an analysis of official statistics over a 15-year period, from 2006 to 2020. The study also includes comparisons of incidence rates between urban and rural areas. A comprehensive search was conducted to identify policy documents that regulate the provision of primary, secondary, and tertiary prevention of cardiovascular diseases. Additionally, official data on the incidence of arterial hypertension, ischemic heart disease, acute myocardial infarction, and cerebrovascular disease were extracted from official statistics, disaggregated by urban and rural areas. Forecast modeling was utilized to project disease incidences up to 2030. The study reveals that Kazakhstan primarily focuses on tertiary prevention of cardiovascular diseases, with less attention given to secondary prevention, and primary prevention is virtually non-existent. In general, screening for arterial hypertension appears to be more successful than for ischemic heart disease. The incidence of arterial hypertension has increased threefold for urban residents and 1.7-fold for rural residents. In urban areas, residents saw a twofold increase in ischemic heart disease incidence, while it remained the same in rural areas. The findings of this study have practical implications for decision-makers, who can use the results to enhance the effectiveness of existing CVD prevention strategies.