UNASSIGNED: The inconvenience of social and behavioural deficits after cerebral ischaemia reperfusion (I/R) injury is still not well documented.
UNASSIGNED: We aimed to study the protective effect of preconditioning swimming exercise combined with melatonin against cerebral I/R induced injury.
UNASSIGNED: Sixty rats were allocated into 6 groups; groups I and II served as control. Groups 3,4,5,6 subjected to bilateral carotid ligation for 30 minutes (min.) followed by reperfusion. Group 3 left untreated while groups 4 and 6; underwent swimming exercise 30 min/day, five days a week for three weeks before the surgery. Groups 5 and 6 treated with melatonin 30 minutes before the operation, then, all rats in groups 4, 5,6 were subjected to I/R. After that, groups 5 and 6 treated with 2nd dose of melatonin 30 minutes after reperfusion.
UNASSIGNED: Combined strategy exhibited the most neuroprotective effect through prevention of cerebral I/R induced inflammation, oxidative stress and apoptosis with subsequent improvement in socio behaviour deficits and enhanced Glial cell proliferative capacity.
UNASSIGNED: The protective contribution of combined strategy is associated with modulation in Macrophage-stimulating 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (MST1/MAPK/ERK) pathway which may explain, at least in part, its protective potential.
Preconditioning swimming exercise combined with melatonin protected against cerebral I/R induced socio-behavioural deficit.Cerebral I/R induced pathophysiological alterations in Prefrontal cortical neurons (PFC) are prevented by combined Preconditioning swimming exercise and melatoninCombined Preconditioning swimming exercise/melatonin in cerebral I/R modulates MST1/MAPK/ERK signalling pathwayCombined Preconditioning swimming exercise/melatonin inhibit inflammation, oxidative stress and apoptosis, thus enhance Glial cell proliferative capacity in I/R induced injury in PFC neurons.

OBJECTIVE: The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA.
METHODS: Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis.
RESULTS: Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model\'s predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes.
CONCLUSIONS: In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

Recent years have seen the publication of several high-profile, negative trials about pressure wires. This has coincided with a consistent increase in the ratio of angioplasty for acute coronary syndromes versus percutaneous coronary intervention in stable coronary artery disease, a greater use of intracoronary imaging during percutaneous coronary intervention and the continued evolution of computational fluid dynamics-derived estimations of fractional flow reserve from both CT and invasive coronary angiography. Consequently, many interventional cardiologists now wonder if the pressure wire will soon become obsolete. This head-to-head article provides a critical appraisal of recent trial data, discusses a potential evolution in how pressure wires are used and debates the motion that the device (and by extension, invasive assessment of coronary physiology) has now had its day.

UNASSIGNED: A strong association between fatty liver disease (FLD) and coronary artery disease is consistently reported. Our aim was to evaluate whether FLD diagnosed using low-dose non-contrast computed tomography (LDCT), as a by-product of myocardial perfusion imaging (MPI), is associated with myocardial ischaemia or left ventricular function parameters.
UNASSIGNED: We analysed 742 patients who had undergone MPI using single photon emission computed tomography (SPECT) and LDCT. A liver-to-spleen ratio (in Hounsfield units) of <1 was defined as FLD. Myocardial ischaemia was defined as a summed difference score (SDS) ≥3. Left ventricular size and systolic function were assessed from the electrocardiogram-gated SPECT. FLD patients were younger (63 vs. 68 years) and had a higher body mass index (34.6 vs. 29.0 kg/m2) and a higher SDS (2.65 vs. 1.63), P < 0.001 for all. Independently of several possible confounding factors including traditional risk factors, patients with FLD had a 1.70-fold risk of ischaemia (95% confidence interval 1.11-2.58, P = 0.014). Left ventricular end-diastolic volume (109 vs. 109 mL) and ejection fraction (61 vs. 61%) were comparable in those with and without FLD (non-significant for both).
UNASSIGNED: With the help of LDCT, it is possible to identify FLD, which is associated with an increased risk of myocardial ischaemia. Therefore, evaluation of FLD from LDCT is recommended along with MPI.
Fatty liver disease is the most common liver disease, affecting a quarter of the population worldwide. It is connected to diabetes and high blood pressure as well as to overweight and obesity. Computed tomography is a common diagnostic method. Its downside is that it exposes patients to radiation. Images can be taken with lower doses of radiation, but these images are less clear and often cannot be used for diagnosis. Low-dose computed tomography is often used with other methods of medical imaging, especially for the heart and lungs. This study shows that fatty liver disease can be diagnosed as a free by-product of low-dose computed tomography images gathered as part of other diagnostic imaging. We also show that fatty liver disease diagnosed from these images is connected to reduced blood flow of heart muscle. Based on the findings, we recommend that these images be scanned for fatty liver disease to identify patients who are at higher risk of heart disease.

BACKGROUND: A growing proportion of people experience incomplete recovery months after contracting coronavirus disease 2019 (COVID-19). These COVID-19 survivors develop a condition known as post-COVID syndrome (PCS), where COVID-19 symptoms persist for > 12 weeks after acute infection. Limited studies have investigated PCS risk factors that notably include pre-existing cardiovascular diseases (CVD), which should be examined considering the most recent PCS data. This review aims to identify CVD as a risk factor for PCS development in COVID-19 survivors.
METHODS: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist, systematic literature searches were performed in the PubMed, Scopus, and Web of Science databases from the earliest date available to June 2023. Data from observational studies in English that described the association between CVD and PCS in adults (≥ 18 years old) were included. A minimum of two authors independently performed the screening, study selection, data extraction, data synthesis, and quality assessment (Newcastle-Ottawa Scale). The protocol of this review was registered under PROSPERO (ID: CRD42023440834).
RESULTS: In total, 594 studies were screened after duplicates and non-original articles had been removed. Of the 11 included studies, CVD including hypertension (six studies), heart failure (three studies), and others (two studies) were significantly associated with PCS development with different factors considered. The included studies were of moderate to high methodological quality.
CONCLUSIONS: Our review highlighted that COVID-19 survivors with pre-existing CVD have a significantly greater risk of developing PCS symptomology than survivors without pre-existing CVD. As heart failure, hypertension and other CVD are associated with a higher risk of developing PCS, comprehensive screening and thorough examinations are essential to minimise the impact of PCS and improve patients\' disease progression.

BACKGROUND: The mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We determined its effects on cerebral perfusion, oxygenation, and temperature, and plasma levels of inflammatory biomarkers, nitrates, nitrites, and ascorbate in ovine Gram-negative sepsis.
METHODS: Sepsis was induced by i.v. infusion of live Escherichia coli for 31 h in unanaesthetised Merino ewes instrumented with a combination sensor in the frontal cerebral cortex to measure tissue perfusion, oxygenation, and temperature. Fluid resuscitation at 23 h was followed by i.v. megadose sodium ascorbate (0.5 g kg-1 over 30 min+0.5 g kg-1 h-1 for 6.5 h) or vehicle (n=6 per group). Norepinephrine was titrated to restore mean arterial pressure (MAP) to 70-80 mm Hg.
RESULTS: At 23 h of sepsis, MAP (mean [sem]: 85 [2] to 64 [2] mm Hg) and plasma ascorbate (27 [2] to 15 [1] μM) decreased (both P<0.001). Cerebral ischaemia (901 [58] to 396 [40] units), hypoxia (34 [1] to 19 [3] mm Hg), and hyperthermia (39.5 [0.1]°C to 40.8 [0.1]°C) (all P<0.001) developed, accompanied by malaise and lethargy. Sodium ascorbate restored cerebral perfusion (703 [121] units], oxygenation (30 [2] mm Hg), temperature (39.2 [0.1]°C) (all PTreatment<0.05), and the behavioural state to normal. Sodium ascorbate slightly reduced the sepsis-induced increase in interleukin-6, returned VEGF-A to normal (both PGroupxTime<0.01), and increased plasma ascorbate (20 000 [300] μM; PGroup<0.001). The effects of sodium ascorbate were not reproduced by equimolar sodium bicarbonate.
CONCLUSIONS: Megadose sodium ascorbate rapidly reversed sepsis-induced cerebral ischaemia, hypoxia, hyperthermia, and sickness behaviour. These effects were not reproduced by an equimolar sodium load.

BACKGROUND: Ancillary diagnostic methods to enhance the accuracy of viability assessment have not been established for use in clinical practice.
OBJECTIVE: To assess intestinal microperfusion measured by Laser Doppler Flowmetry and Spectrophotometry (LDFS) in naturally occurring small intestinal strangulations of different origins and to compare this between viable and non-viable segments.
METHODS: Prospective clinical trial.
METHODS: Forty horses undergoing colic surgery for naturally occurring small intestinal strangulations were included. Tissue oxygen saturation (tSO2), haemoglobin (tHB) and blood flow (tBF) were determined by LDFS before and after release of the strangulation. Intestinal biopsies were taken in cases that underwent intestinal resection or intraoperative euthanasia and assessed using a semi-quantitative mucosal injury score (MIS). The LDFS measurements were compared between the different categories of strangulation causes and histopathological injury using parametric and non-parametric tests (p < 0.05).
RESULTS: Strangulations by pedunculated lipomas had lower tBF (13.9 ± 18 arbitrary units [AU]) than epiploic foramen entrapments (65.2 ± 61 AU; CI -1.697 to -0.2498; p = 0.005). Segments with MIS > 5 showed lower tBF during strangulation than segments with MIS < 4 (mean difference 61.1 AU; CI -1.119 to -0.07361; p = 0.03). This did not differ significantly following release of strangulation. Furthermore, there was a positive correlation between the inflammatory cell count and tBF during strangulation (r 0.34; CI 0.01 to 0.60; p = 0.04). The tSO2 and tHB did not differ between the different categories of lesions or injury.
CONCLUSIONS: No biopsies could be taken from the intestinal segments that did not undergo resection. The duration of strangulation could not reliably be ascertained.
CONCLUSIONS: Blood flow measurements in naturally occurring strangulating lesions show a varying degree of ischaemia in different causes of strangulation. Intestinal blood flow measurements prior to release of the strangulation could potentially contribute to the identification of mucosal injury, yet a high individual variability and other contributing factors need to be considered.

UNASSIGNED: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI.
UNASSIGNED: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay.
UNASSIGNED: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor.
UNASSIGNED: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion. ATTM protected the heart (24-h histological examination) in a drug-exposure-dependent manner (r2 = 0.58, p < 0.05). Blood troponin T levels were significantly (p < 0.05) lower in ATTM-treated animals while myocardial glutathione peroxidase activity, an antioxidant selenoprotein, was elevated (p < 0.05). Overall, our study represents a significant advance in the development of sulfides as therapeutics and underlines the potential of ATTM as a novel adjunct therapy for reperfusion injury. Mechanistically, our study suggests that modulating selenoprotein activity could represent an additional mode of action of sulfide-releasing drugs.

BACKGROUND: To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD).
METHODS: The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[18F]FDG and [68Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts.
RESULTS: Due to a cellular adaptation to hypoxia, a gradual increase in [68Ga]Ga-NOTA-c(NGR) and 2-[18F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction (p ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups.
CONCLUSIONS: The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD.